fulvestrant profile

Fulvestrant: An estradiol derivative and estrogen receptor antagonist that is used for the treatment of estrogen receptor-positive, locally advanced or metastatic breast cancer. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

fulvestrant : A 3-hydroxy steroid that is 17beta-estradiol in which the 7alpha hydrogen has been replaced by a nonyl group in which one of the hydrogens of the terminal methyl has been replaced by a (4,4,5,5,5-pentafluoropentyl)sulfinyl group. An estrogen receptor antagonist, it is used in the treatment of breast cancer. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Pathways (1)

fulvestrant is involved in 1 pathway(s), involving a total of 98 unique proteins and 18 unique compounds

ID Source	ID
PubMed CID	104741
CHEMBL ID	1358
CHEBI ID	31638
SCHEMBL ID	8209
MeSH ID	M0397101

Synonym
BIDD:ER0348
BIDD:PXR0136
AC-4693
AB01273957-01
AB01273957-02
gtpl1015
ici182780
13-methyl-7-[9-(4,5,5,5-pentafluoropentylsulfinyl)nonyl]-7,8,9,11,12,13,14,15,16,17-decahydro-6h-cyclopenta[a]phenanthrene-3,17-diol
129453-61-8
faslodex(ici 182,780)
estra-1,5(10)-triene-3,17-diol, 7-[9-[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl]-, (7.alpha.,17.beta.)-
(7r,8s,9s,13s,14s,17s)-13-methyl-7-[9-(4,4,5,5,5-pentafluoropentylsulfinyl) nonyl]-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol
faslodex
zd-182780
zd-9238
zm-182780
ici-182780
estra-1,3,5(10)-triene-3,17-diol, 7-(9-((4,4,5,5,5-pentafluoropentyl)sulfinyl)nonyl)-, (7alpha,17beta)-
7alpha-(9-((4,4,5,5,5-pentafluoropentyl)sulfinyl)nonyl)estra-1,3,5(10)-triene-3,17beta-diol
ici 182,780
c32h47f5o3s
fulvestrant [usan]
zm 182780
zd 182780
(7r,13s,17s)-13-methyl-7-(9-(4,4,5,5,5-pentafluoropentylsulfinyl)nonyl)-7,8,9,11,12,13,14,15,16,17-decahydro-6h-cyclopenta[a]phenanthrene-3,17-diol
7alpha-{9-[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl}estra-1(10),2,4-triene-3,17beta-diol
CHEBI:31638 ,
fulvestrantum
(7alpha,17beta)-7-{9-[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl}estra-1(10),2,4-triene-3,17-diol
DB00947
NCGC00024964-02
fulvestrant
nsc-719276
nsc719276
faslodex (tn)
fulvestrant (jan/usp/inn)
D01161
(7alpha,17beta)-7-{9-[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl}estra-1,3,5(10)-triene-3,17-diol
ici 182780
7alpha-[9[(4,4,5,5,5-pentafluropentyl)sulfinyl]nonyl]-estra-1,3,5(10)-triene-3, 17 beta diol
ici 182,789
HMS2090N22
NCGC00164789-02
CHEMBL1358 ,
nsc-759879
zd9238
(13s,17s)-13-methyl-7-[9-(4,4,5,5,5-pentafluoro-pentane-1-sulfinyl)-nonyl]-7,8,9,11,12,13,14,15,16,17-decahydro-6h-cyclopenta[a]phenanthrene-3,17-diol
(7r,13s,17s)-13-methyl-7-[9-(4,4,5,5,5-pentafluoro-pentane-1-sulfinyl)-nonyl]-7,8,9,11,12,13,14,15,16,17-decahydro-6h-cyclopenta[a]phenanthrene-3,17-diol
(7r,8r,9s,13s,14s,17s)-13-methyl-7-[9-(4,4,5,5,5-pentafluoro-pentane-1-sulfinyl)-nonyl]-7,8,9,11,12,13,14,15,16,17-decahydro-6h-cyclopenta[a]phenanthrene-3,17-diol
fluvestrant
(7r,8r,9s,13s,14s,17s)-13-methyl-7-(9-(4,4,5,5,5-pentafluoropentylsulfinyl)nonyl)-7,8,9,11,12,13,14,15,16,17-decahydro-6h-cyclopenta[a]phenanthrene-3,17-diol
13-methyl-7-[9-(4,4,5,5,5-pentafluoro-pentane-1-sulfinyl)-nonyl]-7,8,9,11,12,13,14,15,16,17-decahydro-6h-cyclopenta[a]phenanthrene-3,17-diol
bdbm50169743
(7r,8r,9s,13s,14s,17s)-13-methyl-7-(9-(4,4,5,5,5-pentafluoropentyldihydrosulfinyl)nonyl)-7,8,9,11,12,13,14,15,16,17-decahydro-6h-cyclopenta[a]phenanthrene-3,17-diol
(7r,8r,9s,13s,14s,17s)-13-methyl-7-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)nonyl]-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol
HMS3260G10
dtxcid202369
tox21_303656
cas-129453-61-8
dtxsid4022369 ,
NCGC00257357-01
NCGC00260152-01
tox21_202604
tox21_110939
BCP9000707
HY-13636
CS-1267
nsc 759879
unii-22x328qoc4
fulvestrant [usan:usp:inn:ban]
hsdb 7658
ccris 8741
22x328qoc4 ,
BCP0726000227
fulvestrant (faslodex)
LP00114
AKOS015895669
CCG-221418
CCG-220082
smr001456109
MLS006010187
SCHEMBL8209
NCGC00164789-04
tox21_110939_1
AB01273957-03
tox21_500114
NCGC00260799-01
S1191
fulvestrant [ep monograph]
fulvestrant [mart.]
7.alpha.-(9-(4,4,5,5,5-pentafluoropentylsulphinyl)nonyl)estra-1,3,5(10)-triene-3,17.beta.-diol
fulvestrant [orange book]
fulvestrant [jan]
fulvestrant [mi]
fulvestrant [inn]
fulvestrant [usp impurity]
fulvestrant [ema epar]
fulvestrant [vandf]
fulvestrant [usp-rs]
fulvestrant [who-dd]
fulvestrant [usp monograph]
estra-1,3,5(10)-triene-3,17-diol, 7-(9-((4,4,5,5,5-pentafluoropentyl)sulfinyl)nonyl)-, (7.alpha.,17.beta.)-
(7r,8r,9s,13s,14s,17s)-13-methyl-7-(9-((4,4,5,5,5-pentafluoropentyl)sulfinyl)nonyl)-7,8,9,11,12,13,14,15,16,17-decahydro-6h-cyclopenta[a]phenanthrene-3,17-diol
AB01273957_04
(7?,17?)-7-[9-[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol
J-005680
EX-A959
zd 9238
fulvestrant, united states pharmacopeia (usp) reference standard
fulvestrant, >98% (hplc)
fulvestrant, vetec(tm) reagent grade, >98%
fulvestrant, european pharmacopoeia (ep) reference standard
fulvestrant for system suitability, european pharmacopoeia (ep) reference standard
estra-1,3,5(10)-triene-3,17-diol, 7-[9-[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl]-, (7alpha,17beta)-
VWUXBMIQPBEWFH-WCCTWKNTSA-N ,
HMS3712A06
7alpha-[9-(4,4,5,5,5-pentafluoro-pentylsulfinyl)nonyl]estra-1,3,5(10)-triene-3,17beta-diol
7alpha,17beta-[9-[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol
ici 182,780 (fulvestrant)
HB2501
Q5508491
AS-13024
fulvestrant s enantiomer
ici 182 780
BRD-A85667082-001-12-7
SDCCGSBI-0633685.P001
NCGC00386134-10
(7r,9s,13s,14s,17s)-13-methyl-7-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)nonyl]-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol
ici 182780- bio-x
BI167222
EN300-120628
(1s,3as,3br,4r,9bs,11as)-11a-methyl-4-[9-(4,4,5,5,5-pentafluoropentanesulfinyl)nonyl]-1h,2h,3h,3ah,3bh,4h,5h,9bh,10h,11h,11ah-cyclopenta[a]phenanthrene-1,7-diol
fulvestrant (mart.)
fulvestrant (ep monograph)
fulvestrant (usp-rs)
fulvestrant (usp monograph)
7alpha-(9-(4,4,5,5,5-pentafluoropentylsulphinyl)nonyl)estra-1,3,5(10)-triene-3,17beta-diol
fulvestrant (usan:usp:inn:ban)
7a-(9-((4,4,5,5,5,-pentafluoropentyl)sulphinyl)nonyl)-estra-1,3,5(10)-triene-3,17b-diol
fulvestrant (usp impurity)
7alpha-(9-((4,4,5,5,5-pentafluoropentyl)sulfinyl)nonyl)estra-1(10),2,4-triene-3,17beta-diol
l02ba03
F1144
fulvestrant (standard)
CS-0694849
HY-13636R

Excerpt	Reference
"Fulvestrant is a steroid-based, selective estrogen receptor degrader (SERD) that both antagonizes and degrades ER-α and is active in patients who have progressed on antihormonal agents."	( Aparicio, A; Bonnefous, C; Brigham, D; Darimont, B; Douglas, K; Govek, S; Grillot, K; Hager, JH; Heyman, R; Joseph, JD; Julien, J; Kahraman, M; Kaufman, J; Lai, A; Lee, KJ; Lu, N; Moon, MJ; Nagasawa, J; Prudente, R; Qian, J; Rix, PJ; Sensintaffar, J; Shao, G; Smith, ND, 2015)
"Fulvestrant is a steroid-based, selective estrogen receptor degrader (SERD) that both antagonizes and degrades ER-α and shows some activity in patients who have progressed on antihormonal agents."	( Aparicio, A; Bonnefous, C; Brigham, D; Darimont, B; Douglas, K; Govek, S; Hager, JH; Heyman, R; Joseph, JD; Kahraman, M; Kaufman, J; Lai, A; Lee, K; Lu, N; Maheu, K; Nagasawa, J; Prudente, R; Qian, J; Rix, PJ; Sensintaffar, J; Shao, G; Smith, ND, 2018)
"Fulvestrant is a selective oestrogen receptor (ER) degrader used in postmenopausal women with hormone receptor-positive advanced breast cancer. "	( Board, RE; Flynn, M; Guppy, AE; Hanna, D; Jayaweera, HK; Keshwani, K; King, J; Konstantis, A; Lerner, A; Murphy, R; Okines, A; Raja, F; Rehman, F; Roylance, R; Sanderson, B; Sharkey, E; Spurrell, E; Takeuchi, E; Westbury, C, 2022)
"Fulvestrant is a selective estrogen receptor downregulator (SERD) that is approved for first- or second-line use as a single agent or in combination with cyclin dependent kinase or phosphatidylinositol 3-kinase inhibitors for the treatment of metastatic breast cancer. "	( Andreano, KJ; Bae, Y; Blitzer, JT; Chao, CA; Desautels, TK; Heetderks, KA; McDonnell, DP; Norris, JD; Wardell, SE; Yllanes, AP, 2020)
"Fulvestrant is a selective oestrogen receptor (ER) degrader used as monotherapy and combination therapy for ER positive HER2 negative advanced breast cancer (ABC) in postmenopausal women. "	( Balslev, E; Bogovic, J; Buhl, ASK; Buhl, IK; Christensen, IJ; Christensen, TD; Danø, H; Ejlertsen, B; Glavicic, V; Hansen, A; Jakobsen, EH; Jensen, PB; Knoop, AS; Knudsen, S; Langkjer, ST; Linnet, S; Luczak, A; Nielsen, D; Rasmussen, A, 2020)
"Fulvestrant 500 mg is a feasible and promising hormonal maintenance strategy in patients with ER-positive/HER2-negative advanced breast cancer who have no disease progression after first-line chemotherapy."	( Lu, Q; Ouyang, Q; Pang, D; Peng, R; Shi, Y; Wang, S; Xia, W; Xu, F; Yuan, Z; Zheng, Q, 2021)
"Fulvestrant is a steroidal selective estrogen receptor degrader that was approved by the US FDA in 2002 for treatment of ER-positive metastatic breast cancer (ER + MBC) post-progression on aromatase inhibitors. "	( Ellis, MJ; Shafaee, MN, 2018)
"Fulvestrant is a selective estrogen receptor down regulator (SERD)."	( Hanif, R; Ismail, M; Jabeen, I; Khalid, S; Mansoor, Q, 2018)
"Fulvestrant (Ful) is an effective and widely used agent for first- and second-line treatment of hormone receptor-positive, human epidermal growth factor receptor-2-negative (HR+/HER2-) metastatic breast cancer (MBC). "	( Chen, Z; Gong, C; Hu, S; Hu, X; Li, Y; Wang, B; Wang, L; Xie, Y; Yuan, P; Zhang, J; Zhang, Y; Zhao, Y, 2019)
"Fulvestrant 500 mg is an effective and safe treatment for patients with advanced or recurrent breast cancer after prior endocrine treatment."	( E Nagai, S; Futsuhara, K; Hata, S; Inoue, K; Kaneko, S; Kimizuka, K; Kurosumi, M; Nakano, S; Saito, T; Sakurai, T; Yamada, H, 2019)
"Fulvestrant is a highly active systemic therapy in patients with metastatic hormone receptor positive breast cancer. "	( Haaland, B; Lopes, G; Montero, AJ; Tan, PS, 2013)
"Fulvestrant is a representative pure antiestrogen and a Selective Estrogen Receptor Down-regulator (SERD). "	( Coser, KR; McSweeney, KR; Rivizzigno, D; Shioda, K; Shioda, T; Yeh, WL, 2013)
"Fulvestrant is an endocrine agent which degrades the estrogen receptor, thereby downregulating its signaling. "	( Al-Mubarak, M; Amir, E; Ocana, A; Sacher, AG; Seruga, B; Vera-Badillo, F, 2013)
"Fulvestrant is a pure ER-antagonist with a distinct mechanism, of which efficacy has not yet been reported in ESS."	( Arts, HJ; Glaudemans, AW; Hollema, H; Hospers, GA; Reyners, AK; van Kruchten, M, 2013)
"Fulvestrant is a selective estrogen receptor antagonist. "	( Anderson, E; Hansen, A; Jensen, T; Knudsen, S; Kuter, I; Laing, N; Lindemann, J; Mazin, W, 2014)
"Fulvestrant is a selective estrogen receptor down-regulator (SERD) that has demonstrated activity and efficacy in patients with hormone receptor-positive breast cancer previously untreated or treated with hormonal therapy."	( Arroyo Vozmediano, ML; Blanco, M; Calderón, MJ; Ciruelos, E; Cortes-Funes, H; Manso, L; Muñoz, C; Parrilla, L; Pascual, T; Sancho, B; Vega, E, 2014)
"Fulvestrant is an estrogen receptor (ER) antagonist approved for the treatment of postmenopausal women with ER+ advanced breast cancer after failure of prior antiestrogen therapy."	( Anderson, E; Garnett, S; Gee, JM; Kuter, I; Lindemann, J; Nicholson, RI; Robertson, JF, 2014)
"Fulvestrant is an efficient treatment option for these AI-resistant breast cancer cells, and the cell lines will be useful tools to disclose the underlying molecular mechanism for resistance to the different AIs."	( Hansen, SK; Hole, S; Lundqvist, J; Lykkesfeldt, AE; Pedersen, AM; Yde, CW, 2015)
"Fulvestrant 500 mg is an effective and well-tolerated treatment for postmenopausal women with metastatic breast cancer that had progressed after prior endocrine therapies. "	( Araki, K; Fukada, I; Hosoda, M; Ichinokawa, K; Ishida, N; Ito, Y; Iwase, T; Kobayashi, K; Kobayashi, T; Sakai, T; Takahashi, S; Yamamoto, M; Yamashita, H, 2016)
"Fulvestrant is a novel endocrine therapy for breast cancer that exerts both anti-estrogenic and down-regulatory effects by binding to and degrading estrogen receptors (ERs). "	( Egawa, C; Okishiro, M; Takatsuka, Y, 2015)
"Fulvestrant is a dose dependent selective estrogen receptor (ER) down-regulator (SERD) used in ER-positive metastatic breast cancer (MBC). "	( Aung, K; Brown, ME; Cannell, EM; Chianese, DA; Connelly, MC; Darga, EP; Hayes, DF; Henry, NL; Kidwell, KM; Larios, JM; Muñiz, MC; Paoletti, C; Rae, JM; Schott, AF; Thomas, DG; Tokudome, N, 2016)
"Fulvestrant is an estrogen receptor (ER) antagonist and an approved treatment for metastatic estrogen receptor-positive (ER"	( Barry, WT; Biagioni, C; Bonechi, M; Brown, M; De Tribolet-Hardy, J; Guarducci, C; Jeselsohn, R; Laing, N; Leo, AD; Malorni, L; Migliaccio, I; Winer, EP; Zhao, J, 2016)
"Fulvestrant is a selective estrogen receptor down-regulator (SERD) with demonstrated activity and efficacy in the treatment of these patients."	( Blondeaux, E; Del Mastro, L; Lambertini, M; Levaggi, A; Poggio, F; Pronzato, P; Vaglica, M, 2016)
"Fulvestrant is a new type of selective estrogen receptor (ER) downregulator and a promising endocrine therapy for breast cancer."	( Fan, W; Huang, Y; Jiang, D; Sui, M; Wang, X, 2017)
"Fulvestrant is a selective oestrogen receptor down-regulator (SERD), which by blocking proliferation of breast cancer cells, is an effective endocrine treatment for women with hormone-sensitive advanced breast cancer. "	( Goodwin, A; Lee, CI; Wilcken, N, 2017)
"Fulvestrant is an estrogen receptor (ER) antagonist that binds, blocks and degrades the estrogen receptor and is currently used in adjuvant treatment in postmenopausal women with ER-positive breast cancer as an alternative for tamoxifen. "	( Brinkhuis, M; Franke, HR; Jansen, GH; Vermes, I; Wolbers, F, 2008)
"Fulvestrant is a pure ER-antagonist."	( Bartsch, R; Gnant, M; Greil, R; Mlineritsch, B; Niernberger, T; Pluschnig, U; Pober, M; Rudas, M; Sevelda, P; Steger, GG; Thaler, J; Wenzel, C; Zielinski, CC, 2009)
"Fulvestrant was found to be a cost-effective treatment option when added to the treatment sequence as a second- or third-line hormonal therapy for advanced disease."	( Cameron, DA; Camidge, DR; Hirsch, M; Oyee, J, 2008)
"Fulvestrant (Flv) is a pure antiestrogen without agonist activity. "	( Alonso Muñoz, A; García Alfonso, P; Martínez Marín, V; Muñoz Martín, AJ; Pérez Manga, G; Viñuela Benéitez, MC, 2009)
"Fulvestrant is a pure anti-estrogen hormoal agent formally lacking any estrogen-agonist activity. "	( Amoroso, D; Camerini, A; Donati, S; Garrone, O; Mattiot, VP; Porta, RP; Puccetti, C; Puccinelli, P; Rondini, M; Sgambato, A; Siclari, O; Tartarelli, G; Valsuani, C; Vincenti, M, 2009)
"Fulvestrant is an effective and well-tolerated drug for treatment of metastatic estrogen-sensitive breast cancer. "	( Borges, VF; Kabos, P, 2010)
"Fulvestrant is a novel endocrine therapy for breast cancer, with a unique structure and mode of action. "	( Cheung, KL; Johnston, SJ, 2010)
"Fulvestrant is a selective estrogen receptor downregulator (SERD) and highly effective antagonist to hormone-sensitive breast cancers following failure of previous tamoxifen or aromatase inhibitor therapies. "	( Burow, ME; Croce, CM; Devlin, C; Di Leva, G; Fang, F; Hartman-Frey, C; Ivan, M; Li, M; Nephew, KP; Rao, X, 2011)
"Fulvestrant (Faslodex®) is an intramuscularly administered steroidal estrogen receptor antagonist that is devoid of any known estrogen agonist effects. "	( Croxtall, JD; McKeage, K, 2011)
"Fulvestrant is a pure estrogen antagonist that binds, blocks and downgrades the estrogen receptor (ER). "	( Di Leo, A; Moretti, E; Oakman, C; Santarpia, L, 2011)
"Fulvestrant is a selective ER down-regulator that lacks agonist effects on ERα/ERβ, is inactive on ERRγ, but acts as a full agonist on GPER."	( Fitts, JM; Klein, RM; Powers, CA, 2011)
"Fulvestrant is an antiestrogen therapy with a unique mechanism of action. "	( Brown, M; Come, SE; Scott, SM, 2011)
"Fulvestrant is an estrogen receptor antagonist with no known agonist effects that has been shown to be as effective as anastrozole following failure on tamoxifen, at the approved dose of 250 mg/mo."	( Howell, A; Sapunar, F, 2011)
"Fulvestrant is a form of endocrine therapy used in the treatment of postmenopausal breast cancer. "	( Januszewski, A; Krell, J; Palmieri, C; Yan, K, 2011)
"Fulvestrant is an estrogen receptor antagonist indicated for the treatment of hormone receptor-positive metastatic breast cancer (MBC) in postmenopausal women with disease progression following antiestrogen therapy. "	( Litsas, G, 2011)
"Fulvestrant is a selective estrogen receptor downregulator, behaving as a complete antagonist. "	( Alvarez, I; Estévez, L; Fernández, Y; Lluch, A; Muñoz, M; Seguí, MA; Tusquets, I, 2013)
"Fulvestrant is a novel type of endocrine treatment and is considered to be a potent inhibitor of breast cancer cell proliferation. "	( Park, JB, 2013)
"Fulvestrant ("Faslodex") is a new oestrogen receptor antagonist that downregulates the oestrogen receptor and has no known agonist effect."	( Addo, S; Laight, A; Yates, RA, 2002)
"Fulvestrant is an estrogen receptor (ER) antagonist, which, unlike the SERMs, has no known agonist (estrogenic) effect and downregulates the ER protein."	( Morris, C; Wakeling, A, 2002)
"Fulvestrant ('Faslodex') is a new, well-tolerated, oestrogen receptor antagonist that has no known agonist effect and is at least as effective as the AI anastrozole for the treatment of postmenopausal patients with metastatic or advanced breast cancer who have progressed on prior endocrine therapy."	( Parker, LM; Piccart, M; Pritchard, KI, 2003)
"Fulvestrant (ICI 182,780) is a new type of estrogen receptor (ER) antagonist that down-regulates the ER and has no known agonist effects. "	( Buzdar, A; Come, SE; Ellis, M; Gertler, S; Howell, A; Jones, SE; Kleeberg, UR; Mauriac, L; Morris, C; Osborne, CK; Robertson, JF; Vergote, I; Webster, A, 2003)
"Fulvestrant (Faslodex) is a novel estrogen receptor (ER) antagonist that competitively binds to the ER with a much greater affinity than that of tamoxifen. "	( Curran, MP; McKeage, K; Plosker, GL, 2004)
"Fulvestrant is a new type of oestrogen receptor (ER) antagonist with no agonist activity and a novel pharmacological profile. "	( Harrison, M; Robertson, JF, 2004)
"Fulvestrant ('Faslodex') is a new type of endocrine treatment--an oestrogen receptor (ER) antagonist that downregulates the ER and has no agonist effects. "	( Robertson, JF; Vergote, I, 2004)
"Fulvestrant ('Faslodex') is a new type of endocrine treatment--an oestrogen receptor (ER) antagonist with no agonist effects."	( Johnston, S, 2004)
"Fulvestrant ('Faslodex') is a new estrogen receptor (ER) antagonist that has no agonist effects. "	( Franco, S; Frankel, C; Perez, A; Tan-Chiu, E; Vogel, CL, 2004)
"Fulvestrant is a new type of ER antagonist with no agonist effects and a novel mode of action; it binds, blocks and degrades the ER, leading to a reduction in cellular ER and, consequently, in PgR levels."	( Possinger, K, 2004)
"Fulvestrant ('Faslodex') is a new type of endocrine therapy with a different mode of action to existing treatments."	( Lynn, J, 2004)
"Fulvestrant ('Faslodex') is a new type of steroidal oestrogen receptor (ER) antagonist that downregulates cellular levels of the ER and progesterone receptor and has no agonist activity."	( Beex, L; Come, SE; Jones, SE; Kaufmann, M; Makris, A; Nortier, JW; Possinger, K; Robertson, JF; Rutqvist, LE, 2005)
"Fulvestrant (Faslodex) is a new type of estrogen receptor (ER) antagonist that binds, blocks, and degrades the ER, leading to reduced expression of the progesterone receptor (PgR). "	( Bundred, N, 2005)
"Fulvestrant is a pure antiestrogen that emerged from a systematic medicinal chemistry strategy of modification of long-chain alkyl substitutes in the 7a-position of estradiol. "	( Carlson, RW, 2005)
"Fulvestrant is an estrogen receptor antagonist with no agonist effects. "	( Come, SE; Elledge, RM; Howell, A; Jones, SE; Mauriac, L; Osborne, CK; Pippen, J; Robertson, JF; Vergote, I, 2005)
"Fulvestrant is a new type of estrogen receptor antagonist with no agonist effects, and represents a valuable addition to the range of endocrine treatments available to treat postmenopausal women with advanced breast cancer. "	( Gradishar, W, 2005)
"Fulvestrant ("Faslodex") is a new oestrogen receptor (ER) antagonist with no agonist effects that binds, blocks and degrades the ER."	( Howell, A, 2005)
"Fulvestrant ("Faslodex") is a new oestrogen receptor (ER) antagonist with no agonist effects that is licensed in the USA, Brazil, Europe and elsewhere for the treatment of advanced breast cancer (ABC) in postmenopausal women following progression on other endocrine agents. "	( Gips, M; Kaufman, B; Lluch, A; Mauriac, L; Simon, SD; Steger, GG; Vinholes, J; Wardley, A, 2005)
"Fulvestrant is a new oestrogen receptor (ER) antagonist that is licensed for the treatment of postmenopausal women with advanced breast cancer progressing following antioestrogen treatment and may also be effective in those progressing after non-steroidal aromatase inhibitors. "	( Abram, P; Maass, N; Rea, D; Simon, SD; Steger, GG, 2005)
"Fulvestrant ('Faslodex') is a new oestrogen receptor (ER) antagonist with no agonist effects. "	( Bartsch, R; Gnant, MF; Hussian, D; Jakesz, R; Locker, GJ; Pluschnig, U; Sevelda, U; Steger, GG; Wenzel, C; Zielinski, CC, 2005)
"Fulvestrant is a new type of ER antagonist with no agonist effects that binds, blocks and causes degradation of the ER."	( Johnston, SR; Nicholson, RI, 2005)
"Fulvestrant ('Faslodex') is a new ER antagonist with no agonist effects that binds, blocks and degrades the ER."	( Dowsett, M; Johnston, SR; Martin, LA, 2005)
"Fulvestrant is a new type of oestrogen receptor antagonist with no agonist effects."	( Abram, P; Vergote, I, 2006)
"Fulvestrant ('Faslodex') is a new type of estrogen receptor antagonist with no agonist effects, that reduces cellular levels of both estrogen and progesterone receptors. "	( Howell, A, 2006)
"Fulvestrant is a new ER antagonist with no agonist effects that is as effective as anastrozole in treating patients who have progressed on tamoxifen."	( Dodwell, D; Johnston, S; Wardley, A, 2006)
"Fulvestrant is an antiestrogen that leads to estrogen receptor degradation and has demonstrated efficacy in breast cancer patients who have had disease recurrence or progression after tamoxifen. "	( Bernath, AM; Camoriano, JK; Fishkin, PA; Ingle, JN; Mirchandani, D; Nikcevich, DA; Perez, EA; Rowland, KM; Suman, VJ, 2006)
"Fulvestrant is a well-tolerated treatment and has efficacy against breast cancers that have progressed after therapy with a third-generation AI."	( Bernath, AM; Camoriano, JK; Fishkin, PA; Ingle, JN; Mirchandani, D; Nikcevich, DA; Perez, EA; Rowland, KM; Suman, VJ, 2006)
"Fulvestrant ('Faslodex') is an oestrogen receptor (ER) antagonist with no agonist effects. "	( Adamoli, L; Ascione, G; Catania, C; De Pas, T; Franceschelli, L; Goldhirsch, A; Magni, E; Medici, M; Nolè, F; Sanna, G; Torrisi, R; Verri, E, 2007)
"Fulvestrant (Faslodex) is an oestrogen receptor (ER) antagonist with demonstrated efficacy in patients with advanced and pretreated breast cancer."	( Greil, R; Hauser-Kronberger, C; Mayer, P; Mlineritsch, B; Moik, M; Namberger, K; Psenak, O, 2007)
"Fulvestrant appears to be an efficient and well-tolerated drug even in women with advanced breast cancer progressing after multiple endocrine and/or cytotoxic treatments."	( Greil, R; Hauser-Kronberger, C; Mayer, P; Mlineritsch, B; Moik, M; Namberger, K; Psenak, O, 2007)
"Fulvestrant (Faslodex) is a new estrogen receptor (ER) antagonist with no agonist effects that is licensed for the treatment of postmenopausal women with hormone-sensitive advanced breast cancer (ABC) who have progressed/recurred on prior antiestrogen therapy. "	( Awada, A; Azerad, MA; Becquart, D; Bols, A; Borms, M; Christiaens, MR; Cocquyt, V; De Greve, J; Demol, J; Dirix, L; Fontaine, C; Goeminne, JC; Martens, M; Neven, P; Paridaens, R; Pelgrims, G; Selleslags, J; Stragier, B; Van Dam, P; Van Den Broecke, R; Van Den Weyngaert, D; Vandenhoven, G; Vergote, I; Vindevoghel, A, 2008)
"Fulvestrant (Faslodex) is a pure anti-oestrogen that reduces markers of hormone sensitivity and proliferation in postmenopausal women with oestrogen-receptor (ER)-positive breast cancer. "	( Dixon, JM; Faratian, D; Macaskill, EJ; Renshaw, L; Thomas, JS; White, S; Young, OE, 2008)
"Fulvestrant (Faslodex) is an oestrogen receptor antagonist utilised for the treatment of postmenopausal women with locally advanced or metastatic breast cancer following progression or recurrence on anti-oestrogen therapy."	( Chia, S; Gradishar, W, 2008)
"Fulvestrant (Faslodex) is an estrogen receptor (ER) downregulator under development by AstraZeneca for the potential treatment of breast cancer [172191], [237518], [314472], [349551]. "	( Johnston, SR, 2002)

Excerpt	Reference
"Fulvestrant has a different mechanism of action than other hormonal therapies, including aromatase inhibitors and tamoxifen."	( Litsas, G, 2011)
"Fulvestrant has a steroidal structure that competitively binds to the ER with an affinity much greater than that of tamoxifen."	( Bundred, N, 2005)
"Fulvestrant has a mode of action that is distinct from the AIs and the selective oestrogen receptor modulators, and thus may offer an effective treatment option in the post-AI setting."	( Chia, S; Gradishar, W, 2008)
"The fulvestrant DRP algorithm has previously shown effect in BC."	( Balslev, E; Bogovic, J; Buhl, ASK; Buhl, IK; Christensen, IJ; Christensen, TD; Danø, H; Ejlertsen, B; Glavicic, V; Hansen, A; Jakobsen, EH; Jensen, PB; Knoop, AS; Knudsen, S; Langkjer, ST; Linnet, S; Luczak, A; Nielsen, D; Rasmussen, A, 2020)
"Fulvestrant has been studied as second line or first line treatment for post-menopausal hormone receptor positive breast cancers as a single agent or in combination with AIs."	( Goloubeva, O; Kazi, A; Sabnis, GJ; Schech, A; Yu, S, 2020)
"Fulvestrant 500 mg has been an option for endocrine therapy for advanced or recurrent breast cancer after prior endocrine treatment since November 2011 in Japan. "	( E Nagai, S; Futsuhara, K; Hata, S; Inoue, K; Kaneko, S; Kimizuka, K; Kurosumi, M; Nakano, S; Saito, T; Sakurai, T; Yamada, H, 2019)
"Fulvestrant (ICI-182,780) has recently been shown to effectively suppress prostate cancer cell growth in vitro and in vivo. "	( Chan, QK; Ho, SM; Lau, KM; Leung, YK; Ma, FM; Maranchie, J; Ng, CF; To, KF; Tse, HM, 2014)
"Fulvestrant has poor oral bioavailability and low pharmacodynamic characteristics."	( Bogliolo, S; Cassani, C; Dominoni, M; Ferrero, S; Gardella, B; Iacobone, AD; Orlandini, A; Spinillo, A; Venturini, PL; Viazzo, F, 2017)
"Fulvestrant has been effectively used to treat ERα-positive breast cancer, although resistance remains a critical problem."	( Fujii, R; Gohno, T; Hanamura, T; Hayashi, SI; Kaneko, Y; Nagatomo, T; Niwa, T; Tsuboi, K; Yamaguchi, Y, 2017)
"Fulvestrant has superior efficacy and is a preferred treatment option for patients with hormone receptor-positive locally advanced or metastatic breast cancer who have not received previous endocrine therapy compared with a third-generation aromatase inhibitor, a standard of care for first-line treatment of these patients."	( Bondarenko, IM; Cardona-Huerta, S; Cheung, KL; Dvorkin, M; Ellis, MJ; Fazal, M; Grinsted, LM; Manikhas, A; Noguchi, S; Panasci, L; Philco-Salas, MJ; Robertson, JFR; Rowbottom, J; Ruiz-Borrego, M; Shao, Z; Shparyk, Y; Stuart, M; Trishkina, E, 2016)
"Fulvestrant has reached the clinic via extensive pre-clinical and clinical trials, which demonstrated fulvestrant's unique characteristics and showed that they translate to equivalent or improved clinical efficacy compared to established endocrine agents."	( Cheung, KL; Johnston, SJ, 2010)
"Fulvestrant has shown activity inhibiting estrogen receptor dimerization, and the androgen receptor has been shown to stimulate growth in prostate cancer cell lines."	( Blesa, JM; Candel, VA, 2010)
"Fulvestrant has been studied as both first- and second-line therapy for locally advanced and metastatic breast cancer, but few studies have shown its effect as third-line therapy alone."	( Benevides, CF; Chinen, LT; da Silva, SC; do Nascimento Matias, C; Fanelli, MF; Gimenes, DL; Mello, CA, 2011)
"Fulvestrant has minimal activity in advanced, recurrent, or persistent endometrial carcinoma."	( Bonebrake, A; Covens, AL; Filiaci, V; Gersell, D; Lee, YC; Lutman, CV, 2011)
"Fulvestrant has shown activity in ER-dependent cells that are ligand independent."	( Di Leo, A; Moretti, E; Oakman, C; Santarpia, L, 2011)
"Fulvestrant has a different mechanism of action than other hormonal therapies, including aromatase inhibitors and tamoxifen."	( Litsas, G, 2011)
"Fulvestrant has demonstrated clinical benefit rates of 69% in postmenopausal women with advanced tamoxifen-resistant breast cancer."	( Jones, SE, 2002)
"Fulvestrant has been shown to inhibit the proliferative effects of estrogen on sensitive tissues in vitro and in vivo, and is without apparent measurable estrogenic activity."	( Bross, PF; Cohen, MH; Pazdur, R; Williams, GA, 2002)
"Fulvestrant has recently gained US Food and Drug Administration approval for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy."	( Morris, C; Wakeling, A, 2002)
"Fulvestrant has been shown to significantly reduce cellular levels of the ER and progesterone receptor in both preclinical studies and in clinical trials of postmenopausal women with primary breast cancer."	( Harrison, M; Robertson, JF, 2004)
"Fulvestrant has shown efficacy when used after progression on tamoxifen or anastrozole in postmenopausal women with advanced breast cancer."	( Johnston, S, 2004)
"Fulvestrant has a steroidal structure that competitively binds to the ER with an affinity much greater than that of tamoxifen."	( Bundred, N, 2005)
"Fulvestrant has no uterotrophic effects on the immature or ovariectomized rat and blocks the agonistic effects of estradiol and tamoxifen in a dose-dependent manner."	( Carlson, RW, 2005)
"Fulvestrant has been well tolerated in comparative trials published to date, translating into low study withdrawal rates and maintenance of quality of life."	( Jones, SE; Pippen, J, 2005)
"Fulvestrant has established efficacy in tamoxifen-resistant disease and there is a growing body of evidence demonstrating its efficacy in patients with AI-resistant disease."	( Dowsett, M; Johnston, SR; Martin, LA, 2005)
"Fulvestrant has little effect on sex hormone endocrinology, bone metabolism, and lipid biochemistry and appears unlikely to be the subject or cause of CYP3A4-mediated drug interactions."	( Buzdar, AU; Robertson, JF, 2006)
"Fulvestrant has been shown to be equally effective as the third-generation aromatase inhibitor (AI) anastrozole in postmenopausal patients with hormone-sensitive ABC progressing prior to tamoxifen."	( Amant, F; Berteloot, P; Leunen, K; Neven, P; Van Gorp, T; Vergote, I, 2006)
"Fulvestrant has a mode of action that is distinct from the AIs and the selective oestrogen receptor modulators, and thus may offer an effective treatment option in the post-AI setting."	( Chia, S; Gradishar, W, 2008)
"Fulvestrant also has potential in the treatment of other estrogen-responsive tumors, such as uterine tumors [178081]."	( Johnston, SR, 2002)

Excerpt	Reference
"Fulvestrant could inhibit the glycolysis of GH3 cells by downregulating IRE1/XBP1 signaling pathway, and this process was closely related with the downregulation of PKM2."	( Chang, L; Li, GF; Su, J; Tan, CL; Wang, C; Wang, X; Wen, Y; Xie, LY; Xu, JL; Zhang, DZ; Zhang, XX, 2018)
"Fulvestrant did not inhibit tamoxifen actions to reduce total pituitary protein, again indicating effects not mediated by ERα/ERβ."	( Fitts, JM; Klein, RM; Powers, CA, 2011)
"Fulvestrant may enhance effects of vandetanib in NSCLC by blocking estrogen-driven activation of the EGFR pathway."	( Gubish, CT; Henry, C; Rothstein, ME; Siegfried, JM; Stabile, LP, 2012)
"Fulvestrant caused an increase in circulating levels of oestradiol, irrespective of the stage of the menstrual cycle at which patients commenced treatment."	( Dixon, JM; Faratian, D; Macaskill, EJ; Renshaw, L; Thomas, JS; White, S; Young, OE, 2008)

Excerpt	Reference
"Fulvestrant treatment provided significant radiosensitisation of CAMA-1 and BT-474 cells (rER: 1.06-2.0) but not ZR-75-1 cells (rER: 0.9-1.11)."	( Eisner, JR; Lerner, LM; Michmerhuizen, AR; Pesch, AM; Pierce, LJ; Rae, JM; Schwartz, R; Speers, CW; Ward, C; Wilder-Romans, K; Zhang, A, 2022)
"Fulvestrant-treated mice had either low or undetectable tumor uptake."	( Bénard, F; Langlois, R; Lecomte, R; Ouellet, R; Paquette, M; Phoenix, S; Turcotte, EE; van Lier, JE, 2013)
"Fulvestrant treatment increased phosphorylation of all ErbB family RTKs; however, phospho-RTK upregulation was not seen in tumors treated with both fulvestrant and anti-ErbB3."	( Arteaga, CL; Balko, JM; Cook, RS; Earp, HS; Hicks, DJ; Hutchinson, K; Kuba, MG; Massarweh, S; Morrison, MM; Perou, CM; Prat, A; Sánchez, V; Stanford, JC; Williams, AJ; Williams, MM; Young, C, 2013)
"Fulvestrant treatment, which should mimic aromatase inhibition for regulation through ESR1 and ESR2 signaling but potentially stimulate endogenous estrogen signaling through the G protein-coupled estrogen receptor (GPER), had the opposite effect on aromatase inhibition."	( Berger, T; Conley, AJ; Katleba, KD; Legacki, EL, 2015)
"Fulvestrant use in pretreated metastatic breast cancer patients is associated with variable response rates. "	( Ahmad, I; Amir, E; Chia, S; Clemons, M; Dent, S; Dranitsaris, G; Fralick, M; Freedman, O; Kumar, R; Napolskikh, J; Petrella, T; Rayson, D; Tonkin, K, 2009)
"Fulvestrant treatment of estradiol (E2)- and fulvestrant-sensitive MCF7 cells resulted in increased expression of endogenous miR-221/222."	( Burow, ME; Croce, CM; Devlin, C; Di Leva, G; Fang, F; Hartman-Frey, C; Ivan, M; Li, M; Nephew, KP; Rao, X, 2011)
"Fulvestrant treatment may be an effective therapy for such tumors."	( Leng, L; Zhang, Y, 2011)
"Fulvestrant treatment caused ERalpha degradation in CK8.CK18-positive human breast cancer cells, and CK8 and CK18 depletion by small interference RNAs partially blocked fulvestrant-induced receptor degradation."	( Long, X; Nephew, KP, 2006)
"Fulvestrant treatment was associated with prolonged CB and was well tolerated in this group of heavily pre-treated patients with ABC. "	( Adamoli, L; Ascione, G; Catania, C; De Pas, T; Franceschelli, L; Goldhirsch, A; Magni, E; Medici, M; Nolè, F; Sanna, G; Torrisi, R; Verri, E, 2007)
"Fulvestrant treatment resulted in clinical benefit for 47.9% of patients; 58 patients (27.2%) exhibited an objective response, of whom 3 exhibited a complete response."	( Esparaz, BT; Garnett, SA; Lower, EE; Wade, JL, 2007)
"Treatment with fulvestrant causes ERα down-regulation, an event that helps overcome several resistance mechanisms."	( Chen, HW; Cheung-Lau, G; Comin-Anduix, B; Deng, G; Garcia, AJ; Hamilton, N; Jung, ME; Márquez-Garbán, DC; Pietras, RJ; Xing, Y, 2019)
"Treatment with fulvestrant is not associated with any clinically significant effects on endometrial thickening, bone-specific turnover markers or sex hormone levels."	( Croxtall, JD; McKeage, K, 2011)
"Treatment with fulvestrant decreased (18)F-FFNP, (18)F-FES, and (18)F-FDG uptake and inhibited growth of SSM3 tumors but decreased only (18)F-FES uptake in SSM2 tumors, with no effect on growth, despite both tumors being ERα(+)/PR(+)."	( Carlson, KE; Chan, SR; Dence, CS; Fettig, NM; Fowler, AM; Jeyakumar, M; Katzenellenbogen, JA; Schreiber, RD; Sharp, TL; Welch, MJ; Zhou, D, 2012)
"Treatment with fulvestrant plus metronomic CM was effective in advanced ABC and was minimally toxic providing long-term disease control in a high proportion of patients."	( Adamoli, L; Aurilio, G; Botteri, E; Colleoni, M; Cullurà, D; Curigliano, G; Esposito, A; Goldhirsch, A; Minchella, I; Munzone, E; Nolè, F; Sciandivasci, A, 2012)
"Treatment with fulvestrant has also demonstrated clinical efficacy among patients who progressed following treatment with tamoxifen followed by nonsteroidal aromatase inhibitors."	( Bundred, N, 2005)
"Treatment with fulvestrant, which was also associated with down-regulation of secreted TFPI (9% with 10 nM and 26% with 1000 nM), abolished the TFPI-inhibiting effect of raloxifene, but not of the other compounds."	( Birkenes, B; Dahm, AE; Iversen, N; Ree, AH; Sandset, PM, 2006)

Role	Description
antineoplastic agent	A substance that inhibits or prevents the proliferation of neoplasms.
estrogen receptor antagonist	An antagonist at the estrogen receptor.
estrogen antagonist	A compound which inhibits or antagonises the biosynthesis or actions of estrogens.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Class	Description
3-hydroxy steroid	Any hydroxy steroid carrying a hydroxy group at position 3.
17beta-hydroxy steroid	A 17-hydroxy steroid in which the hydroxy group at position 17 has a beta-configuration.
organofluorine compound	An organofluorine compound is a compound containing at least one carbon-fluorine bond.
sulfoxide	An organosulfur compound having the structure R2S=O or R2C=S=O (R =/= H).
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Pathway	Proteins	Compounds
Integrated breast cancer pathway	98	18

Protein	Taxonomy	Measurement	Average (µ)	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
thioredoxin reductase	Rattus norvegicus (Norway rat)	Potency	13.3714	0.1000	20.8793	79.4328	AID488772; AID588456
RAR-related orphan receptor gamma	Mus musculus (house mouse)	Potency	5.6322	0.0060	38.0041	19,952.5996	AID1159521; AID1159523
ATAD5 protein, partial	Homo sapiens (human)	Potency	7.3048	0.0041	10.8903	31.5287	AID493107
GALC protein	Homo sapiens (human)	Potency	0.7079	28.1838	28.1838	28.1838	AID1159614
GLS protein	Homo sapiens (human)	Potency	31.6228	0.3548	7.9355	39.8107	AID624146
TDP1 protein	Homo sapiens (human)	Potency	5.3091	0.0008	11.3822	44.6684	AID686978
GLI family zinc finger 3	Homo sapiens (human)	Potency	4.4256	0.0007	14.5928	83.7951	AID1259369; AID1259392
AR protein	Homo sapiens (human)	Potency	8.7388	0.0002	21.2231	8,912.5098	AID1259243; AID1259247; AID743035; AID743053; AID743063
estrogen receptor 2 (ER beta)	Homo sapiens (human)	Potency	24.9964	0.0006	57.9133	22,387.1992	AID1259377; AID1259378
nuclear receptor subfamily 1, group I, member 3	Homo sapiens (human)	Potency	8.3727	0.0010	22.6508	76.6163	AID1224838; AID1224893
progesterone receptor	Homo sapiens (human)	Potency	1.5278	0.0004	17.9460	75.1148	AID1346795
cytochrome P450 family 3 subfamily A polypeptide 4	Homo sapiens (human)	Potency	1.5008	0.0123	7.9835	43.2770	AID1346984; AID1645841
glucocorticoid receptor [Homo sapiens]	Homo sapiens (human)	Potency	4.8573	0.0002	14.3764	60.0339	AID720692
estrogen-related nuclear receptor alpha	Homo sapiens (human)	Potency	8.0064	0.0015	30.6073	15,848.9004	AID1224819; AID1224820; AID1224821; AID1224841; AID1224842; AID1224848; AID1224849; AID1259401; AID1259403
farnesoid X nuclear receptor	Homo sapiens (human)	Potency	6.1615	0.3758	27.4851	61.6524	AID743217
pregnane X nuclear receptor	Homo sapiens (human)	Potency	5.9175	0.0054	28.0263	1,258.9301	AID1346982; AID1346985
estrogen nuclear receptor alpha	Homo sapiens (human)	Potency	0.8210	0.0002	29.3054	16,493.5996	AID1259244; AID1259248; AID743069; AID743075; AID743078; AID743079; AID743080; AID743091
G	Vesicular stomatitis virus	Potency	1.3803	0.0123	8.9648	39.8107	AID1645842
peroxisome proliferator-activated receptor delta	Homo sapiens (human)	Potency	11.8823	0.0010	24.5048	61.6448	AID743212
arylsulfatase A	Homo sapiens (human)	Potency	4.7755	1.0691	13.9551	37.9330	AID720538
euchromatic histone-lysine N-methyltransferase 2	Homo sapiens (human)	Potency	0.6702	0.0355	20.9770	89.1251	AID504332
aryl hydrocarbon receptor	Homo sapiens (human)	Potency	25.7523	0.0007	23.0674	1,258.9301	AID743122
cytochrome P450, family 19, subfamily A, polypeptide 1, isoform CRA_a	Homo sapiens (human)	Potency	0.0374	0.0017	23.8393	78.1014	AID743083
activating transcription factor 6	Homo sapiens (human)	Potency	0.0601	0.1434	27.6121	59.8106	AID1159516
nuclear receptor subfamily 1, group I, member 2	Rattus norvegicus (Norway rat)	Potency	28.1838	0.1000	9.1916	31.6228	AID1346983
thyroid hormone receptor beta isoform 2	Rattus norvegicus (Norway rat)	Potency	0.0024	0.0003	23.4451	159.6830	AID743065; AID743067
heat shock protein beta-1	Homo sapiens (human)	Potency	38.8762	0.0420	27.3789	61.6448	AID743210
nuclear factor erythroid 2-related factor 2 isoform 1	Homo sapiens (human)	Potency	32.8599	0.0006	27.2152	1,122.0200	AID743202; AID743219
Voltage-dependent calcium channel gamma-2 subunit	Mus musculus (house mouse)	Potency	0.0044	0.0015	57.7890	15,848.9004	AID1259244
Interferon beta	Homo sapiens (human)	Potency	1.3803	0.0033	9.1582	39.8107	AID1645842
HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)	Potency	1.3803	0.0123	8.9648	39.8107	AID1645842
Cellular tumor antigen p53	Homo sapiens (human)	Potency	23.7101	0.0023	19.5956	74.0614	AID651631
Glutamate receptor 2	Rattus norvegicus (Norway rat)	Potency	0.0044	0.0015	51.7393	15,848.9004	AID1259244
Spike glycoprotein	Severe acute respiratory syndrome-related coronavirus	Potency	39.8107	0.0096	10.5250	35.4813	AID1479145
Inositol hexakisphosphate kinase 1	Homo sapiens (human)	Potency	1.3803	0.0123	8.9648	39.8107	AID1645842
cytochrome P450 2C9, partial	Homo sapiens (human)	Potency	1.3803	0.0123	8.9648	39.8107	AID1645842
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Protein	Taxonomy	Measurement	Average	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
ATP-binding cassette sub-family C member 3	Homo sapiens (human)	IC50 (µMol)	133.0000	0.6315	4.4531	9.3000	AID1473740
Multidrug resistance-associated protein 4	Homo sapiens (human)	IC50 (µMol)	133.0000	0.2000	5.6774	10.0000	AID1473741
Bile salt export pump	Homo sapiens (human)	IC50 (µMol)	133.0000	0.1100	7.1903	10.0000	AID1473738
Estrogen receptor	Homo sapiens (human)	IC50 (µMol)	0.0061	0.0000	0.7237	32.7000	AID1228236; AID1251780; AID1251781; AID1443551; AID1443553; AID1443577; AID1443610; AID1446051; AID1469717; AID1469719; AID1469729; AID1558991; AID1572318; AID1594508; AID1629296; AID1629297; AID1629298; AID1658825; AID1658829; AID1690956; AID1768138; AID1811365; AID1829663; AID1906833; AID248483; AID248712; AID249001; AID297564; AID469727; AID70321; AID70324
Estrogen receptor	Homo sapiens (human)	Ki	0.0031	0.0000	0.4229	7.9070	AID68906; AID68907; AID70002
Estrogen receptor	Rattus norvegicus (Norway rat)	IC50 (µMol)	0.0059	0.0007	4.1521	14.1600	AID650636
Progesterone receptor	Homo sapiens (human)	IC50 (µMol)	50.0001	0.0000	0.5807	10.0000	AID1251782; AID1251783
Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)	Ki	0.0024	0.0001	0.0304	0.1570	AID68906; AID68907
Steroid hormone receptor ERR1	Homo sapiens (human)	IC50 (µMol)	0.0020	0.0020	1.1663	9.6400	AID728186
Bifunctional epoxide hydrolase 2	Homo sapiens (human)	IC50 (µMol)	0.0060	0.0000	0.5450	9.1000	AID755348
Bifunctional epoxide hydrolase 2	Homo sapiens (human)	Ki	0.0260	0.0015	0.0454	0.1560	AID755345
Beta-lactamase TEM	Escherichia coli	IC50 (µMol)	55.9000	0.0019	1.7618	10.0000	AID1616742
Estrogen receptor beta	Homo sapiens (human)	IC50 (µMol)	0.0104	0.0001	0.5294	32.7000	AID1228237; AID1690957; AID1829664; AID1906835; AID242498; AID248483; AID248712; AID249001; AID297565; AID469732; AID70645
Estrogen receptor beta	Homo sapiens (human)	Ki	0.0032	0.0000	0.1251	2.8760	AID68906; AID68907; AID70164
Canalicular multispecific organic anion transporter 1	Homo sapiens (human)	IC50 (µMol)	133.0000	2.4100	6.3433	10.0000	AID1473739
Bile acid receptor	Homo sapiens (human)	IC50 (µMol)	0.7900	0.0183	4.5603	10.0000	AID755454
NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)	IC50 (µMol)	2.6000	0.1000	3.3800	6.6000	AID1742983
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Protein	Taxonomy	Measurement	Average	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)	EC50 (µMol)	1.9500	0.0020	3.5196	10.0000	AID755445
Estrogen receptor	Homo sapiens (human)	EC50 (µMol)	0.0007	0.0000	0.5305	4.4000	AID1228205; AID1535224; AID1594509
Estrogen receptor	Homo sapiens (human)	Kd	0.0047	0.0047	0.0047	0.0047	AID1594514
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Protein	Taxonomy	Measurement	Average	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
Estrogen receptor	Homo sapiens (human)	Activity	0.0001	0.0001	0.0001	0.0001	AID1356847
Estrogen receptor	Homo sapiens (human)	DC50	0.0001	0.0001	0.0304	0.0910	AID1768139
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Process	via Protein(s)	Taxonomy
xenobiotic metabolic process	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
xenobiotic transmembrane transport	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
bile acid and bile salt transport	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
glucuronoside transport	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
xenobiotic transport	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
transmembrane transport	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
leukotriene transport	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
monoatomic anion transmembrane transport	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
transport across blood-brain barrier	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
prostaglandin secretion	Multidrug resistance-associated protein 4	Homo sapiens (human)
cilium assembly	Multidrug resistance-associated protein 4	Homo sapiens (human)
platelet degranulation	Multidrug resistance-associated protein 4	Homo sapiens (human)
xenobiotic metabolic process	Multidrug resistance-associated protein 4	Homo sapiens (human)
xenobiotic transmembrane transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
bile acid and bile salt transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
prostaglandin transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
urate transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
glutathione transmembrane transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
transmembrane transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
cAMP transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
leukotriene transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
monoatomic anion transmembrane transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
export across plasma membrane	Multidrug resistance-associated protein 4	Homo sapiens (human)
transport across blood-brain barrier	Multidrug resistance-associated protein 4	Homo sapiens (human)
guanine nucleotide transmembrane transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
negative regulation of DNA-templated transcription	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
regulation of DNA-templated transcription	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
xenobiotic metabolic process	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
signal transduction	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
steroid metabolic process	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
positive regulation of gene expression	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
intracellular receptor signaling pathway	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
xenobiotic catabolic process	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
xenobiotic transport	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
positive regulation of DNA-templated transcription	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
positive regulation of transcription by RNA polymerase II	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
cell differentiation	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
negative regulation of transcription by RNA polymerase II	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
fatty acid metabolic process	Bile salt export pump	Homo sapiens (human)
bile acid biosynthetic process	Bile salt export pump	Homo sapiens (human)
xenobiotic metabolic process	Bile salt export pump	Homo sapiens (human)
xenobiotic transmembrane transport	Bile salt export pump	Homo sapiens (human)
response to oxidative stress	Bile salt export pump	Homo sapiens (human)
bile acid metabolic process	Bile salt export pump	Homo sapiens (human)
response to organic cyclic compound	Bile salt export pump	Homo sapiens (human)
bile acid and bile salt transport	Bile salt export pump	Homo sapiens (human)
canalicular bile acid transport	Bile salt export pump	Homo sapiens (human)
protein ubiquitination	Bile salt export pump	Homo sapiens (human)
regulation of fatty acid beta-oxidation	Bile salt export pump	Homo sapiens (human)
carbohydrate transmembrane transport	Bile salt export pump	Homo sapiens (human)
bile acid signaling pathway	Bile salt export pump	Homo sapiens (human)
cholesterol homeostasis	Bile salt export pump	Homo sapiens (human)
response to estrogen	Bile salt export pump	Homo sapiens (human)
response to ethanol	Bile salt export pump	Homo sapiens (human)
xenobiotic export from cell	Bile salt export pump	Homo sapiens (human)
lipid homeostasis	Bile salt export pump	Homo sapiens (human)
phospholipid homeostasis	Bile salt export pump	Homo sapiens (human)
positive regulation of bile acid secretion	Bile salt export pump	Homo sapiens (human)
regulation of bile acid metabolic process	Bile salt export pump	Homo sapiens (human)
transmembrane transport	Bile salt export pump	Homo sapiens (human)
cell surface receptor signaling pathway via JAK-STAT	Interferon beta	Homo sapiens (human)
response to exogenous dsRNA	Interferon beta	Homo sapiens (human)
B cell activation involved in immune response	Interferon beta	Homo sapiens (human)
cell surface receptor signaling pathway	Interferon beta	Homo sapiens (human)
cell surface receptor signaling pathway via JAK-STAT	Interferon beta	Homo sapiens (human)
response to virus	Interferon beta	Homo sapiens (human)
positive regulation of autophagy	Interferon beta	Homo sapiens (human)
cytokine-mediated signaling pathway	Interferon beta	Homo sapiens (human)
natural killer cell activation	Interferon beta	Homo sapiens (human)
positive regulation of peptidyl-serine phosphorylation of STAT protein	Interferon beta	Homo sapiens (human)
cellular response to interferon-beta	Interferon beta	Homo sapiens (human)
B cell proliferation	Interferon beta	Homo sapiens (human)
negative regulation of viral genome replication	Interferon beta	Homo sapiens (human)
innate immune response	Interferon beta	Homo sapiens (human)
positive regulation of innate immune response	Interferon beta	Homo sapiens (human)
regulation of MHC class I biosynthetic process	Interferon beta	Homo sapiens (human)
negative regulation of T cell differentiation	Interferon beta	Homo sapiens (human)
positive regulation of transcription by RNA polymerase II	Interferon beta	Homo sapiens (human)
defense response to virus	Interferon beta	Homo sapiens (human)
type I interferon-mediated signaling pathway	Interferon beta	Homo sapiens (human)
neuron cellular homeostasis	Interferon beta	Homo sapiens (human)
cellular response to exogenous dsRNA	Interferon beta	Homo sapiens (human)
cellular response to virus	Interferon beta	Homo sapiens (human)
negative regulation of Lewy body formation	Interferon beta	Homo sapiens (human)
negative regulation of T-helper 2 cell cytokine production	Interferon beta	Homo sapiens (human)
positive regulation of apoptotic signaling pathway	Interferon beta	Homo sapiens (human)
response to exogenous dsRNA	Interferon beta	Homo sapiens (human)
B cell differentiation	Interferon beta	Homo sapiens (human)
natural killer cell activation involved in immune response	Interferon beta	Homo sapiens (human)
adaptive immune response	Interferon beta	Homo sapiens (human)
T cell activation involved in immune response	Interferon beta	Homo sapiens (human)
humoral immune response	Interferon beta	Homo sapiens (human)
positive regulation of T cell mediated cytotoxicity	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
adaptive immune response	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
regulation of T cell anergy	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
defense response	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
immune response	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
detection of bacterium	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
regulation of interleukin-12 production	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
regulation of interleukin-6 production	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
protection from natural killer cell mediated cytotoxicity	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
innate immune response	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
regulation of dendritic cell differentiation	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
antigen processing and presentation of endogenous peptide antigen via MHC class Ib	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
positive regulation of transcription by RNA polymerase II	Estrogen receptor	Homo sapiens (human)
negative regulation of transcription by RNA polymerase II	Estrogen receptor	Homo sapiens (human)
antral ovarian follicle growth	Estrogen receptor	Homo sapiens (human)
epithelial cell development	Estrogen receptor	Homo sapiens (human)
chromatin remodeling	Estrogen receptor	Homo sapiens (human)
regulation of DNA-templated transcription	Estrogen receptor	Homo sapiens (human)
signal transduction	Estrogen receptor	Homo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathway	Estrogen receptor	Homo sapiens (human)
positive regulation of cytosolic calcium ion concentration	Estrogen receptor	Homo sapiens (human)
androgen metabolic process	Estrogen receptor	Homo sapiens (human)
male gonad development	Estrogen receptor	Homo sapiens (human)
negative regulation of gene expression	Estrogen receptor	Homo sapiens (human)
positive regulation of phospholipase C activity	Estrogen receptor	Homo sapiens (human)
intracellular steroid hormone receptor signaling pathway	Estrogen receptor	Homo sapiens (human)
intracellular estrogen receptor signaling pathway	Estrogen receptor	Homo sapiens (human)
response to estradiol	Estrogen receptor	Homo sapiens (human)
regulation of toll-like receptor signaling pathway	Estrogen receptor	Homo sapiens (human)
negative regulation of smooth muscle cell apoptotic process	Estrogen receptor	Homo sapiens (human)
negative regulation of canonical NF-kappaB signal transduction	Estrogen receptor	Homo sapiens (human)
negative regulation of DNA-binding transcription factor activity	Estrogen receptor	Homo sapiens (human)
response to estrogen	Estrogen receptor	Homo sapiens (human)
positive regulation of DNA-templated transcription	Estrogen receptor	Homo sapiens (human)
positive regulation of transcription by RNA polymerase II	Estrogen receptor	Homo sapiens (human)
fibroblast proliferation	Estrogen receptor	Homo sapiens (human)
positive regulation of fibroblast proliferation	Estrogen receptor	Homo sapiens (human)
stem cell differentiation	Estrogen receptor	Homo sapiens (human)
regulation of inflammatory response	Estrogen receptor	Homo sapiens (human)
positive regulation of DNA-binding transcription factor activity	Estrogen receptor	Homo sapiens (human)
RNA polymerase II preinitiation complex assembly	Estrogen receptor	Homo sapiens (human)
uterus development	Estrogen receptor	Homo sapiens (human)
vagina development	Estrogen receptor	Homo sapiens (human)
prostate epithelial cord elongation	Estrogen receptor	Homo sapiens (human)
prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis	Estrogen receptor	Homo sapiens (human)
regulation of branching involved in prostate gland morphogenesis	Estrogen receptor	Homo sapiens (human)
mammary gland branching involved in pregnancy	Estrogen receptor	Homo sapiens (human)
mammary gland alveolus development	Estrogen receptor	Homo sapiens (human)
epithelial cell proliferation involved in mammary gland duct elongation	Estrogen receptor	Homo sapiens (human)
protein localization to chromatin	Estrogen receptor	Homo sapiens (human)
cellular response to estradiol stimulus	Estrogen receptor	Homo sapiens (human)
negative regulation of miRNA transcription	Estrogen receptor	Homo sapiens (human)
regulation of epithelial cell apoptotic process	Estrogen receptor	Homo sapiens (human)
regulation of transcription by RNA polymerase II	Estrogen receptor	Homo sapiens (human)
cellular response to estrogen stimulus	Estrogen receptor	Homo sapiens (human)
negative regulation of cell population proliferation	Cellular tumor antigen p53	Homo sapiens (human)
regulation of cell cycle	Cellular tumor antigen p53	Homo sapiens (human)
regulation of cell cycle G2/M phase transition	Cellular tumor antigen p53	Homo sapiens (human)
DNA damage response	Cellular tumor antigen p53	Homo sapiens (human)
ER overload response	Cellular tumor antigen p53	Homo sapiens (human)
cellular response to glucose starvation	Cellular tumor antigen p53	Homo sapiens (human)
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	Cellular tumor antigen p53	Homo sapiens (human)
regulation of apoptotic process	Cellular tumor antigen p53	Homo sapiens (human)
positive regulation of transcription by RNA polymerase II	Cellular tumor antigen p53	Homo sapiens (human)
positive regulation of miRNA transcription	Cellular tumor antigen p53	Homo sapiens (human)
negative regulation of transcription by RNA polymerase II	Cellular tumor antigen p53	Homo sapiens (human)
mitophagy	Cellular tumor antigen p53	Homo sapiens (human)
in utero embryonic development	Cellular tumor antigen p53	Homo sapiens (human)
somitogenesis	Cellular tumor antigen p53	Homo sapiens (human)
release of cytochrome c from mitochondria	Cellular tumor antigen p53	Homo sapiens (human)
hematopoietic progenitor cell differentiation	Cellular tumor antigen p53	Homo sapiens (human)
T cell proliferation involved in immune response	Cellular tumor antigen p53	Homo sapiens (human)
B cell lineage commitment	Cellular tumor antigen p53	Homo sapiens (human)
T cell lineage commitment	Cellular tumor antigen p53	Homo sapiens (human)
response to ischemia	Cellular tumor antigen p53	Homo sapiens (human)
nucleotide-excision repair	Cellular tumor antigen p53	Homo sapiens (human)
double-strand break repair	Cellular tumor antigen p53	Homo sapiens (human)
regulation of DNA-templated transcription	Cellular tumor antigen p53	Homo sapiens (human)
regulation of transcription by RNA polymerase II	Cellular tumor antigen p53	Homo sapiens (human)
protein import into nucleus	Cellular tumor antigen p53	Homo sapiens (human)
autophagy	Cellular tumor antigen p53	Homo sapiens (human)
DNA damage response	Cellular tumor antigen p53	Homo sapiens (human)
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest	Cellular tumor antigen p53	Homo sapiens (human)
DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator	Cellular tumor antigen p53	Homo sapiens (human)
transforming growth factor beta receptor signaling pathway	Cellular tumor antigen p53	Homo sapiens (human)
Ras protein signal transduction	Cellular tumor antigen p53	Homo sapiens (human)
gastrulation	Cellular tumor antigen p53	Homo sapiens (human)
neuroblast proliferation	Cellular tumor antigen p53	Homo sapiens (human)
negative regulation of neuroblast proliferation	Cellular tumor antigen p53	Homo sapiens (human)
protein localization	Cellular tumor antigen p53	Homo sapiens (human)
negative regulation of DNA replication	Cellular tumor antigen p53	Homo sapiens (human)
negative regulation of cell population proliferation	Cellular tumor antigen p53	Homo sapiens (human)
determination of adult lifespan	Cellular tumor antigen p53	Homo sapiens (human)
mRNA transcription	Cellular tumor antigen p53	Homo sapiens (human)
rRNA transcription	Cellular tumor antigen p53	Homo sapiens (human)
response to salt stress	Cellular tumor antigen p53	Homo sapiens (human)
response to inorganic substance	Cellular tumor antigen p53	Homo sapiens (human)
response to X-ray	Cellular tumor antigen p53	Homo sapiens (human)
response to gamma radiation	Cellular tumor antigen p53	Homo sapiens (human)
positive regulation of gene expression	Cellular tumor antigen p53	Homo sapiens (human)
cardiac muscle cell apoptotic process	Cellular tumor antigen p53	Homo sapiens (human)
positive regulation of cardiac muscle cell apoptotic process	Cellular tumor antigen p53	Homo sapiens (human)
glial cell proliferation	Cellular tumor antigen p53	Homo sapiens (human)
viral process	Cellular tumor antigen p53	Homo sapiens (human)
glucose catabolic process to lactate via pyruvate	Cellular tumor antigen p53	Homo sapiens (human)
cerebellum development	Cellular tumor antigen p53	Homo sapiens (human)
negative regulation of cell growth	Cellular tumor antigen p53	Homo sapiens (human)
DNA damage response, signal transduction by p53 class mediator	Cellular tumor antigen p53	Homo sapiens (human)
negative regulation of transforming growth factor beta receptor signaling pathway	Cellular tumor antigen p53	Homo sapiens (human)
mitotic G1 DNA damage checkpoint signaling	Cellular tumor antigen p53	Homo sapiens (human)
negative regulation of telomere maintenance via telomerase	Cellular tumor antigen p53	Homo sapiens (human)
T cell differentiation in thymus	Cellular tumor antigen p53	Homo sapiens (human)
tumor necrosis factor-mediated signaling pathway	Cellular tumor antigen p53	Homo sapiens (human)
regulation of tissue remodeling	Cellular tumor antigen p53	Homo sapiens (human)
cellular response to UV	Cellular tumor antigen p53	Homo sapiens (human)
multicellular organism growth	Cellular tumor antigen p53	Homo sapiens (human)
positive regulation of mitochondrial membrane permeability	Cellular tumor antigen p53	Homo sapiens (human)
cellular response to glucose starvation	Cellular tumor antigen p53	Homo sapiens (human)
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	Cellular tumor antigen p53	Homo sapiens (human)
positive regulation of apoptotic process	Cellular tumor antigen p53	Homo sapiens (human)
negative regulation of apoptotic process	Cellular tumor antigen p53	Homo sapiens (human)
entrainment of circadian clock by photoperiod	Cellular tumor antigen p53	Homo sapiens (human)
mitochondrial DNA repair	Cellular tumor antigen p53	Homo sapiens (human)
regulation of DNA damage response, signal transduction by p53 class mediator	Cellular tumor antigen p53	Homo sapiens (human)
positive regulation of neuron apoptotic process	Cellular tumor antigen p53	Homo sapiens (human)
transcription initiation-coupled chromatin remodeling	Cellular tumor antigen p53	Homo sapiens (human)
negative regulation of proteolysis	Cellular tumor antigen p53	Homo sapiens (human)
negative regulation of DNA-templated transcription	Cellular tumor antigen p53	Homo sapiens (human)
positive regulation of DNA-templated transcription	Cellular tumor antigen p53	Homo sapiens (human)
positive regulation of RNA polymerase II transcription preinitiation complex assembly	Cellular tumor antigen p53	Homo sapiens (human)
positive regulation of transcription by RNA polymerase II	Cellular tumor antigen p53	Homo sapiens (human)
response to antibiotic	Cellular tumor antigen p53	Homo sapiens (human)
fibroblast proliferation	Cellular tumor antigen p53	Homo sapiens (human)
negative regulation of fibroblast proliferation	Cellular tumor antigen p53	Homo sapiens (human)
circadian behavior	Cellular tumor antigen p53	Homo sapiens (human)
bone marrow development	Cellular tumor antigen p53	Homo sapiens (human)
embryonic organ development	Cellular tumor antigen p53	Homo sapiens (human)
positive regulation of peptidyl-tyrosine phosphorylation	Cellular tumor antigen p53	Homo sapiens (human)
protein stabilization	Cellular tumor antigen p53	Homo sapiens (human)
negative regulation of helicase activity	Cellular tumor antigen p53	Homo sapiens (human)
protein tetramerization	Cellular tumor antigen p53	Homo sapiens (human)
chromosome organization	Cellular tumor antigen p53	Homo sapiens (human)
neuron apoptotic process	Cellular tumor antigen p53	Homo sapiens (human)
regulation of cell cycle	Cellular tumor antigen p53	Homo sapiens (human)
hematopoietic stem cell differentiation	Cellular tumor antigen p53	Homo sapiens (human)
negative regulation of glial cell proliferation	Cellular tumor antigen p53	Homo sapiens (human)
type II interferon-mediated signaling pathway	Cellular tumor antigen p53	Homo sapiens (human)
cardiac septum morphogenesis	Cellular tumor antigen p53	Homo sapiens (human)
positive regulation of programmed necrotic cell death	Cellular tumor antigen p53	Homo sapiens (human)
protein-containing complex assembly	Cellular tumor antigen p53	Homo sapiens (human)
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	Cellular tumor antigen p53	Homo sapiens (human)
thymocyte apoptotic process	Cellular tumor antigen p53	Homo sapiens (human)
positive regulation of thymocyte apoptotic process	Cellular tumor antigen p53	Homo sapiens (human)
necroptotic process	Cellular tumor antigen p53	Homo sapiens (human)
cellular response to hypoxia	Cellular tumor antigen p53	Homo sapiens (human)
cellular response to xenobiotic stimulus	Cellular tumor antigen p53	Homo sapiens (human)
cellular response to ionizing radiation	Cellular tumor antigen p53	Homo sapiens (human)
cellular response to gamma radiation	Cellular tumor antigen p53	Homo sapiens (human)
cellular response to UV-C	Cellular tumor antigen p53	Homo sapiens (human)
stem cell proliferation	Cellular tumor antigen p53	Homo sapiens (human)
signal transduction by p53 class mediator	Cellular tumor antigen p53	Homo sapiens (human)
intrinsic apoptotic signaling pathway by p53 class mediator	Cellular tumor antigen p53	Homo sapiens (human)
reactive oxygen species metabolic process	Cellular tumor antigen p53	Homo sapiens (human)
cellular response to actinomycin D	Cellular tumor antigen p53	Homo sapiens (human)
positive regulation of release of cytochrome c from mitochondria	Cellular tumor antigen p53	Homo sapiens (human)
cellular senescence	Cellular tumor antigen p53	Homo sapiens (human)
replicative senescence	Cellular tumor antigen p53	Homo sapiens (human)
oxidative stress-induced premature senescence	Cellular tumor antigen p53	Homo sapiens (human)
intrinsic apoptotic signaling pathway	Cellular tumor antigen p53	Homo sapiens (human)
oligodendrocyte apoptotic process	Cellular tumor antigen p53	Homo sapiens (human)
positive regulation of execution phase of apoptosis	Cellular tumor antigen p53	Homo sapiens (human)
negative regulation of mitophagy	Cellular tumor antigen p53	Homo sapiens (human)
regulation of mitochondrial membrane permeability involved in apoptotic process	Cellular tumor antigen p53	Homo sapiens (human)
regulation of intrinsic apoptotic signaling pathway by p53 class mediator	Cellular tumor antigen p53	Homo sapiens (human)
positive regulation of miRNA transcription	Cellular tumor antigen p53	Homo sapiens (human)
negative regulation of G1 to G0 transition	Cellular tumor antigen p53	Homo sapiens (human)
negative regulation of miRNA processing	Cellular tumor antigen p53	Homo sapiens (human)
negative regulation of glucose catabolic process to lactate via pyruvate	Cellular tumor antigen p53	Homo sapiens (human)
negative regulation of pentose-phosphate shunt	Cellular tumor antigen p53	Homo sapiens (human)
intrinsic apoptotic signaling pathway in response to hypoxia	Cellular tumor antigen p53	Homo sapiens (human)
regulation of fibroblast apoptotic process	Cellular tumor antigen p53	Homo sapiens (human)
negative regulation of reactive oxygen species metabolic process	Cellular tumor antigen p53	Homo sapiens (human)
positive regulation of reactive oxygen species metabolic process	Cellular tumor antigen p53	Homo sapiens (human)
negative regulation of stem cell proliferation	Cellular tumor antigen p53	Homo sapiens (human)
positive regulation of cellular senescence	Cellular tumor antigen p53	Homo sapiens (human)
positive regulation of intrinsic apoptotic signaling pathway	Cellular tumor antigen p53	Homo sapiens (human)
ovulation from ovarian follicle	Progesterone receptor	Homo sapiens (human)
glandular epithelial cell maturation	Progesterone receptor	Homo sapiens (human)
regulation of DNA-templated transcription	Progesterone receptor	Homo sapiens (human)
signal transduction	Progesterone receptor	Homo sapiens (human)
G protein-coupled receptor signaling pathway	Progesterone receptor	Homo sapiens (human)
cell-cell signaling	Progesterone receptor	Homo sapiens (human)
positive regulation of gene expression	Progesterone receptor	Homo sapiens (human)
negative regulation of gene expression	Progesterone receptor	Homo sapiens (human)
paracrine signaling	Progesterone receptor	Homo sapiens (human)
negative regulation of phosphorylation	Progesterone receptor	Homo sapiens (human)
positive regulation of transcription by RNA polymerase II	Progesterone receptor	Homo sapiens (human)
lung alveolus development	Progesterone receptor	Homo sapiens (human)
regulation of epithelial cell proliferation	Progesterone receptor	Homo sapiens (human)
progesterone receptor signaling pathway	Progesterone receptor	Homo sapiens (human)
maintenance of protein location in nucleus	Progesterone receptor	Homo sapiens (human)
tertiary branching involved in mammary gland duct morphogenesis	Progesterone receptor	Homo sapiens (human)
regulation of transcription by RNA polymerase II	Progesterone receptor	Homo sapiens (human)
intracellular steroid hormone receptor signaling pathway	Progesterone receptor	Homo sapiens (human)
negative regulation of endothelial cell proliferation	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
leukocyte chemotaxis involved in inflammatory response	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
leukocyte migration involved in inflammatory response	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
leukotriene production involved in inflammatory response	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
leukotriene metabolic process	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
humoral immune response	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
negative regulation of angiogenesis	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
leukotriene biosynthetic process	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
lipoxygenase pathway	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
positive regulation of bone mineralization	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
dendritic cell migration	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
glucose homeostasis	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
long-chain fatty acid biosynthetic process	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
regulation of fat cell differentiation	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
regulation of inflammatory response	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
negative regulation of inflammatory response	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
regulation of insulin secretion	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
negative regulation of vascular wound healing	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
negative regulation of wound healing	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
regulation of inflammatory response to wounding	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
regulation of cytokine production involved in inflammatory response	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
regulation of cellular response to oxidative stress	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
leukotriene A4 biosynthetic process	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
regulation of reactive oxygen species biosynthetic process	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
negative regulation of response to endoplasmic reticulum stress	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
negative regulation of sprouting angiogenesis	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
positive regulation of leukocyte adhesion to arterial endothelial cell	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
lipoxin biosynthetic process	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
arachidonic acid metabolic process	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
lipid oxidation	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
regulation of DNA-templated transcription	Steroid hormone receptor ERR1	Homo sapiens (human)
positive regulation of transcription by RNA polymerase II	Steroid hormone receptor ERR1	Homo sapiens (human)
intracellular steroid hormone receptor signaling pathway	Steroid hormone receptor ERR1	Homo sapiens (human)
regulation of transcription by RNA polymerase II	Steroid hormone receptor ERR1	Homo sapiens (human)
response to toxic substance	Bifunctional epoxide hydrolase 2	Homo sapiens (human)
positive regulation of gene expression	Bifunctional epoxide hydrolase 2	Homo sapiens (human)
dephosphorylation	Bifunctional epoxide hydrolase 2	Homo sapiens (human)
cholesterol homeostasis	Bifunctional epoxide hydrolase 2	Homo sapiens (human)
stilbene catabolic process	Bifunctional epoxide hydrolase 2	Homo sapiens (human)
phospholipid dephosphorylation	Bifunctional epoxide hydrolase 2	Homo sapiens (human)
regulation of cholesterol metabolic process	Bifunctional epoxide hydrolase 2	Homo sapiens (human)
epoxide metabolic process	Bifunctional epoxide hydrolase 2	Homo sapiens (human)
inositol phosphate metabolic process	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
phosphatidylinositol phosphate biosynthetic process	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
negative regulation of cold-induced thermogenesis	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
inositol phosphate biosynthetic process	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
negative regulation of transcription by RNA polymerase II	Estrogen receptor beta	Homo sapiens (human)
regulation of DNA-templated transcription	Estrogen receptor beta	Homo sapiens (human)
signal transduction	Estrogen receptor beta	Homo sapiens (human)
cell-cell signaling	Estrogen receptor beta	Homo sapiens (human)
negative regulation of cell growth	Estrogen receptor beta	Homo sapiens (human)
intracellular estrogen receptor signaling pathway	Estrogen receptor beta	Homo sapiens (human)
positive regulation of DNA-templated transcription	Estrogen receptor beta	Homo sapiens (human)
positive regulation of DNA-binding transcription factor activity	Estrogen receptor beta	Homo sapiens (human)
cellular response to estradiol stimulus	Estrogen receptor beta	Homo sapiens (human)
regulation of transcription by RNA polymerase II	Estrogen receptor beta	Homo sapiens (human)
cellular response to estrogen stimulus	Estrogen receptor beta	Homo sapiens (human)
xenobiotic metabolic process	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
xenobiotic transmembrane transport	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
negative regulation of gene expression	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
bile acid and bile salt transport	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
bilirubin transport	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
heme catabolic process	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
xenobiotic export from cell	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
transmembrane transport	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
transepithelial transport	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
leukotriene transport	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
monoatomic anion transmembrane transport	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
transport across blood-brain barrier	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
xenobiotic transport across blood-brain barrier	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
negative regulation of very-low-density lipoprotein particle remodeling	Bile acid receptor	Homo sapiens (human)
positive regulation of DNA-templated transcription	Bile acid receptor	Homo sapiens (human)
negative regulation of transcription by RNA polymerase II	Bile acid receptor	Homo sapiens (human)
nitrogen catabolite activation of transcription from RNA polymerase II promoter	Bile acid receptor	Homo sapiens (human)
intracellular glucose homeostasis	Bile acid receptor	Homo sapiens (human)
regulation of transcription by RNA polymerase II	Bile acid receptor	Homo sapiens (human)
transcription by RNA polymerase II	Bile acid receptor	Homo sapiens (human)
inflammatory response	Bile acid receptor	Homo sapiens (human)
cell-cell junction assembly	Bile acid receptor	Homo sapiens (human)
Notch signaling pathway	Bile acid receptor	Homo sapiens (human)
bile acid metabolic process	Bile acid receptor	Homo sapiens (human)
negative regulation of tumor necrosis factor-mediated signaling pathway	Bile acid receptor	Homo sapiens (human)
regulation of low-density lipoprotein particle clearance	Bile acid receptor	Homo sapiens (human)
intracellular receptor signaling pathway	Bile acid receptor	Homo sapiens (human)
negative regulation of type II interferon production	Bile acid receptor	Homo sapiens (human)
negative regulation of interleukin-1 production	Bile acid receptor	Homo sapiens (human)
negative regulation of interleukin-2 production	Bile acid receptor	Homo sapiens (human)
negative regulation of interleukin-6 production	Bile acid receptor	Homo sapiens (human)
negative regulation of tumor necrosis factor production	Bile acid receptor	Homo sapiens (human)
positive regulation of interleukin-17 production	Bile acid receptor	Homo sapiens (human)
toll-like receptor 9 signaling pathway	Bile acid receptor	Homo sapiens (human)
regulation of urea metabolic process	Bile acid receptor	Homo sapiens (human)
intracellular triglyceride homeostasis	Bile acid receptor	Homo sapiens (human)
positive regulation of insulin secretion involved in cellular response to glucose stimulus	Bile acid receptor	Homo sapiens (human)
bile acid signaling pathway	Bile acid receptor	Homo sapiens (human)
intracellular bile acid receptor signaling pathway	Bile acid receptor	Homo sapiens (human)
cholesterol homeostasis	Bile acid receptor	Homo sapiens (human)
defense response to bacterium	Bile acid receptor	Homo sapiens (human)
negative regulation of apoptotic process	Bile acid receptor	Homo sapiens (human)
negative regulation of canonical NF-kappaB signal transduction	Bile acid receptor	Homo sapiens (human)
innate immune response	Bile acid receptor	Homo sapiens (human)
positive regulation of transcription by RNA polymerase II	Bile acid receptor	Homo sapiens (human)
positive regulation of insulin receptor signaling pathway	Bile acid receptor	Homo sapiens (human)
fatty acid homeostasis	Bile acid receptor	Homo sapiens (human)
regulation of insulin secretion involved in cellular response to glucose stimulus	Bile acid receptor	Homo sapiens (human)
regulation of bile acid biosynthetic process	Bile acid receptor	Homo sapiens (human)
cellular response to lipopolysaccharide	Bile acid receptor	Homo sapiens (human)
cellular response to fatty acid	Bile acid receptor	Homo sapiens (human)
cellular response to organonitrogen compound	Bile acid receptor	Homo sapiens (human)
negative regulation of monocyte chemotactic protein-1 production	Bile acid receptor	Homo sapiens (human)
regulation of cholesterol metabolic process	Bile acid receptor	Homo sapiens (human)
cellular response to bile acid	Bile acid receptor	Homo sapiens (human)
positive regulation of adipose tissue development	Bile acid receptor	Homo sapiens (human)
positive regulation of phosphatidic acid biosynthetic process	Bile acid receptor	Homo sapiens (human)
positive regulation of glutamate metabolic process	Bile acid receptor	Homo sapiens (human)
positive regulation of ammonia assimilation cycle	Bile acid receptor	Homo sapiens (human)
cell differentiation	Bile acid receptor	Homo sapiens (human)
negative regulation of inflammatory response	Bile acid receptor	Homo sapiens (human)
protein deacetylation	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
protein deacetylation	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
mitochondrion organization	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
regulation of ketone biosynthetic process	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
negative regulation of cardiac muscle cell apoptotic process	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
response to nutrient levels	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
protein demalonylation	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
peptidyl-lysine demalonylation	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
protein desuccinylation	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
peptidyl-lysine desuccinylation	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
protein deglutarylation	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
negative regulation of reactive oxygen species metabolic process	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
epigenetic regulation of gene expression	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Process	via Protein(s)	Taxonomy
ATP binding	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
ABC-type xenobiotic transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
glucuronoside transmembrane transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
ABC-type glutathione S-conjugate transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
ABC-type bile acid transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
ATP hydrolysis activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
ATPase-coupled transmembrane transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
xenobiotic transmembrane transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
icosanoid transmembrane transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
ABC-type transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
guanine nucleotide transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
protein binding	Multidrug resistance-associated protein 4	Homo sapiens (human)
ATP binding	Multidrug resistance-associated protein 4	Homo sapiens (human)
ABC-type xenobiotic transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
prostaglandin transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
urate transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
purine nucleotide transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
ABC-type glutathione S-conjugate transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
ABC-type bile acid transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
efflux transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
15-hydroxyprostaglandin dehydrogenase (NAD+) activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
ATP hydrolysis activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
glutathione transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
ATPase-coupled transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
xenobiotic transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
ABC-type transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
RNA polymerase II transcription regulatory region sequence-specific DNA binding	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
DNA-binding transcription factor activity, RNA polymerase II-specific	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
DNA-binding transcription activator activity, RNA polymerase II-specific	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
nuclear receptor activity	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
protein binding	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
zinc ion binding	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
nuclear receptor binding	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
sequence-specific double-stranded DNA binding	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
RNA polymerase II cis-regulatory region sequence-specific DNA binding	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
protein binding	Bile salt export pump	Homo sapiens (human)
ATP binding	Bile salt export pump	Homo sapiens (human)
ABC-type xenobiotic transporter activity	Bile salt export pump	Homo sapiens (human)
bile acid transmembrane transporter activity	Bile salt export pump	Homo sapiens (human)
canalicular bile acid transmembrane transporter activity	Bile salt export pump	Homo sapiens (human)
carbohydrate transmembrane transporter activity	Bile salt export pump	Homo sapiens (human)
ABC-type bile acid transporter activity	Bile salt export pump	Homo sapiens (human)
ATP hydrolysis activity	Bile salt export pump	Homo sapiens (human)
cytokine activity	Interferon beta	Homo sapiens (human)
cytokine receptor binding	Interferon beta	Homo sapiens (human)
type I interferon receptor binding	Interferon beta	Homo sapiens (human)
protein binding	Interferon beta	Homo sapiens (human)
chloramphenicol O-acetyltransferase activity	Interferon beta	Homo sapiens (human)
TAP binding	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
signaling receptor binding	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
protein binding	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
peptide antigen binding	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
TAP binding	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
protein-folding chaperone binding	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
RNA polymerase II cis-regulatory region sequence-specific DNA binding	Estrogen receptor	Homo sapiens (human)
DNA-binding transcription factor activity, RNA polymerase II-specific	Estrogen receptor	Homo sapiens (human)
TFIIB-class transcription factor binding	Estrogen receptor	Homo sapiens (human)
transcription coregulator binding	Estrogen receptor	Homo sapiens (human)
transcription corepressor binding	Estrogen receptor	Homo sapiens (human)
transcription coactivator binding	Estrogen receptor	Homo sapiens (human)
DNA-binding transcription activator activity, RNA polymerase II-specific	Estrogen receptor	Homo sapiens (human)
chromatin binding	Estrogen receptor	Homo sapiens (human)
DNA-binding transcription factor activity	Estrogen receptor	Homo sapiens (human)
nuclear receptor activity	Estrogen receptor	Homo sapiens (human)
steroid binding	Estrogen receptor	Homo sapiens (human)
protein binding	Estrogen receptor	Homo sapiens (human)
calmodulin binding	Estrogen receptor	Homo sapiens (human)
beta-catenin binding	Estrogen receptor	Homo sapiens (human)
zinc ion binding	Estrogen receptor	Homo sapiens (human)
TBP-class protein binding	Estrogen receptor	Homo sapiens (human)
enzyme binding	Estrogen receptor	Homo sapiens (human)
protein kinase binding	Estrogen receptor	Homo sapiens (human)
nitric-oxide synthase regulator activity	Estrogen receptor	Homo sapiens (human)
nuclear estrogen receptor activity	Estrogen receptor	Homo sapiens (human)
nuclear estrogen receptor binding	Estrogen receptor	Homo sapiens (human)
estrogen response element binding	Estrogen receptor	Homo sapiens (human)
identical protein binding	Estrogen receptor	Homo sapiens (human)
ATPase binding	Estrogen receptor	Homo sapiens (human)
14-3-3 protein binding	Estrogen receptor	Homo sapiens (human)
sequence-specific double-stranded DNA binding	Estrogen receptor	Homo sapiens (human)
transcription cis-regulatory region binding	Cellular tumor antigen p53	Homo sapiens (human)
RNA polymerase II cis-regulatory region sequence-specific DNA binding	Cellular tumor antigen p53	Homo sapiens (human)
DNA-binding transcription factor activity, RNA polymerase II-specific	Cellular tumor antigen p53	Homo sapiens (human)
cis-regulatory region sequence-specific DNA binding	Cellular tumor antigen p53	Homo sapiens (human)
core promoter sequence-specific DNA binding	Cellular tumor antigen p53	Homo sapiens (human)
TFIID-class transcription factor complex binding	Cellular tumor antigen p53	Homo sapiens (human)
DNA-binding transcription repressor activity, RNA polymerase II-specific	Cellular tumor antigen p53	Homo sapiens (human)
DNA-binding transcription activator activity, RNA polymerase II-specific	Cellular tumor antigen p53	Homo sapiens (human)
protease binding	Cellular tumor antigen p53	Homo sapiens (human)
p53 binding	Cellular tumor antigen p53	Homo sapiens (human)
DNA binding	Cellular tumor antigen p53	Homo sapiens (human)
chromatin binding	Cellular tumor antigen p53	Homo sapiens (human)
DNA-binding transcription factor activity	Cellular tumor antigen p53	Homo sapiens (human)
mRNA 3'-UTR binding	Cellular tumor antigen p53	Homo sapiens (human)
copper ion binding	Cellular tumor antigen p53	Homo sapiens (human)
protein binding	Cellular tumor antigen p53	Homo sapiens (human)
zinc ion binding	Cellular tumor antigen p53	Homo sapiens (human)
enzyme binding	Cellular tumor antigen p53	Homo sapiens (human)
receptor tyrosine kinase binding	Cellular tumor antigen p53	Homo sapiens (human)
ubiquitin protein ligase binding	Cellular tumor antigen p53	Homo sapiens (human)
histone deacetylase regulator activity	Cellular tumor antigen p53	Homo sapiens (human)
ATP-dependent DNA/DNA annealing activity	Cellular tumor antigen p53	Homo sapiens (human)
identical protein binding	Cellular tumor antigen p53	Homo sapiens (human)
histone deacetylase binding	Cellular tumor antigen p53	Homo sapiens (human)
protein heterodimerization activity	Cellular tumor antigen p53	Homo sapiens (human)
protein-folding chaperone binding	Cellular tumor antigen p53	Homo sapiens (human)
protein phosphatase 2A binding	Cellular tumor antigen p53	Homo sapiens (human)
RNA polymerase II-specific DNA-binding transcription factor binding	Cellular tumor antigen p53	Homo sapiens (human)
14-3-3 protein binding	Cellular tumor antigen p53	Homo sapiens (human)
MDM2/MDM4 family protein binding	Cellular tumor antigen p53	Homo sapiens (human)
disordered domain specific binding	Cellular tumor antigen p53	Homo sapiens (human)
general transcription initiation factor binding	Cellular tumor antigen p53	Homo sapiens (human)
molecular function activator activity	Cellular tumor antigen p53	Homo sapiens (human)
promoter-specific chromatin binding	Cellular tumor antigen p53	Homo sapiens (human)
RNA polymerase II cis-regulatory region sequence-specific DNA binding	Progesterone receptor	Homo sapiens (human)
DNA-binding transcription factor activity, RNA polymerase II-specific	Progesterone receptor	Homo sapiens (human)
transcription coactivator binding	Progesterone receptor	Homo sapiens (human)
DNA-binding transcription activator activity, RNA polymerase II-specific	Progesterone receptor	Homo sapiens (human)
DNA binding	Progesterone receptor	Homo sapiens (human)
nuclear steroid receptor activity	Progesterone receptor	Homo sapiens (human)
G protein-coupled receptor activity	Progesterone receptor	Homo sapiens (human)
steroid binding	Progesterone receptor	Homo sapiens (human)
protein binding	Progesterone receptor	Homo sapiens (human)
zinc ion binding	Progesterone receptor	Homo sapiens (human)
enzyme binding	Progesterone receptor	Homo sapiens (human)
identical protein binding	Progesterone receptor	Homo sapiens (human)
ATPase binding	Progesterone receptor	Homo sapiens (human)
estrogen response element binding	Progesterone receptor	Homo sapiens (human)
nuclear receptor activity	Progesterone receptor	Homo sapiens (human)
arachidonate 5-lipoxygenase activity	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
arachidonate 12(S)-lipoxygenase activity	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
iron ion binding	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
protein binding	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
hydrolase activity	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
arachidonate 8(S)-lipoxygenase activity	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
DNA-binding transcription factor activity, RNA polymerase II-specific	Steroid hormone receptor ERR1	Homo sapiens (human)
DNA-binding transcription factor activity	Steroid hormone receptor ERR1	Homo sapiens (human)
nuclear steroid receptor activity	Steroid hormone receptor ERR1	Homo sapiens (human)
steroid binding	Steroid hormone receptor ERR1	Homo sapiens (human)
protein binding	Steroid hormone receptor ERR1	Homo sapiens (human)
zinc ion binding	Steroid hormone receptor ERR1	Homo sapiens (human)
protein domain specific binding	Steroid hormone receptor ERR1	Homo sapiens (human)
sequence-specific DNA binding	Steroid hormone receptor ERR1	Homo sapiens (human)
sequence-specific double-stranded DNA binding	Steroid hormone receptor ERR1	Homo sapiens (human)
estrogen response element binding	Steroid hormone receptor ERR1	Homo sapiens (human)
nuclear receptor activity	Steroid hormone receptor ERR1	Homo sapiens (human)
magnesium ion binding	Bifunctional epoxide hydrolase 2	Homo sapiens (human)
epoxide hydrolase activity	Bifunctional epoxide hydrolase 2	Homo sapiens (human)
toxic substance binding	Bifunctional epoxide hydrolase 2	Homo sapiens (human)
phosphatase activity	Bifunctional epoxide hydrolase 2	Homo sapiens (human)
10-hydroxy-9-(phosphonooxy)octadecanoate phosphatase activity	Bifunctional epoxide hydrolase 2	Homo sapiens (human)
lipid phosphatase activity	Bifunctional epoxide hydrolase 2	Homo sapiens (human)
protein homodimerization activity	Bifunctional epoxide hydrolase 2	Homo sapiens (human)
lysophosphatidic acid phosphatase activity	Bifunctional epoxide hydrolase 2	Homo sapiens (human)
inositol-1,3,4,5,6-pentakisphosphate kinase activity	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
inositol hexakisphosphate kinase activity	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
inositol heptakisphosphate kinase activity	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
inositol hexakisphosphate 5-kinase activity	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
protein binding	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
ATP binding	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
inositol hexakisphosphate 1-kinase activity	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
inositol hexakisphosphate 3-kinase activity	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
inositol 5-diphosphate pentakisphosphate 5-kinase activity	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
inositol diphosphate tetrakisphosphate kinase activity	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
RNA polymerase II cis-regulatory region sequence-specific DNA binding	Estrogen receptor beta	Homo sapiens (human)
DNA-binding transcription factor activity, RNA polymerase II-specific	Estrogen receptor beta	Homo sapiens (human)
DNA binding	Estrogen receptor beta	Homo sapiens (human)
nuclear steroid receptor activity	Estrogen receptor beta	Homo sapiens (human)
nuclear receptor activity	Estrogen receptor beta	Homo sapiens (human)
steroid binding	Estrogen receptor beta	Homo sapiens (human)
protein binding	Estrogen receptor beta	Homo sapiens (human)
zinc ion binding	Estrogen receptor beta	Homo sapiens (human)
enzyme binding	Estrogen receptor beta	Homo sapiens (human)
nuclear estrogen receptor activity	Estrogen receptor beta	Homo sapiens (human)
estrogen response element binding	Estrogen receptor beta	Homo sapiens (human)
receptor antagonist activity	Estrogen receptor beta	Homo sapiens (human)
protein binding	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
ATP binding	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
organic anion transmembrane transporter activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
ABC-type xenobiotic transporter activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
bilirubin transmembrane transporter activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
ABC-type glutathione S-conjugate transporter activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
ATP hydrolysis activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
ATPase-coupled transmembrane transporter activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
xenobiotic transmembrane transporter activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
ABC-type transporter activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
RNA polymerase II transcription regulatory region sequence-specific DNA binding	Bile acid receptor	Homo sapiens (human)
RNA polymerase II cis-regulatory region sequence-specific DNA binding	Bile acid receptor	Homo sapiens (human)
DNA-binding transcription factor activity, RNA polymerase II-specific	Bile acid receptor	Homo sapiens (human)
transcription coregulator binding	Bile acid receptor	Homo sapiens (human)
DNA-binding transcription activator activity, RNA polymerase II-specific	Bile acid receptor	Homo sapiens (human)
DNA-binding transcription factor activity	Bile acid receptor	Homo sapiens (human)
nuclear receptor activity	Bile acid receptor	Homo sapiens (human)
protein binding	Bile acid receptor	Homo sapiens (human)
zinc ion binding	Bile acid receptor	Homo sapiens (human)
nuclear receptor binding	Bile acid receptor	Homo sapiens (human)
bile acid binding	Bile acid receptor	Homo sapiens (human)
bile acid receptor activity	Bile acid receptor	Homo sapiens (human)
sequence-specific DNA binding	Bile acid receptor	Homo sapiens (human)
nuclear retinoid X receptor binding	Bile acid receptor	Homo sapiens (human)
chenodeoxycholic acid binding	Bile acid receptor	Homo sapiens (human)
NAD+ ADP-ribosyltransferase activity	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
NAD+-protein ADP-ribosyltransferase activity	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
zinc ion binding	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
NAD-dependent protein lysine deacetylase activity	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
protein-malonyllysine demalonylase activity	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
protein-succinyllysine desuccinylase activity	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
protein-glutaryllysine deglutarylase activity	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
NAD+ binding	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Process	via Protein(s)	Taxonomy
plasma membrane	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
basal plasma membrane	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
basolateral plasma membrane	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
membrane	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
nucleolus	Multidrug resistance-associated protein 4	Homo sapiens (human)
Golgi apparatus	Multidrug resistance-associated protein 4	Homo sapiens (human)
plasma membrane	Multidrug resistance-associated protein 4	Homo sapiens (human)
membrane	Multidrug resistance-associated protein 4	Homo sapiens (human)
basolateral plasma membrane	Multidrug resistance-associated protein 4	Homo sapiens (human)
apical plasma membrane	Multidrug resistance-associated protein 4	Homo sapiens (human)
platelet dense granule membrane	Multidrug resistance-associated protein 4	Homo sapiens (human)
external side of apical plasma membrane	Multidrug resistance-associated protein 4	Homo sapiens (human)
plasma membrane	Multidrug resistance-associated protein 4	Homo sapiens (human)
nucleoplasm	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
transcription regulator complex	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
nuclear body	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
intermediate filament cytoskeleton	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
chromatin	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
nucleus	Nuclear receptor subfamily 1 group I member 2	Homo sapiens (human)
basolateral plasma membrane	Bile salt export pump	Homo sapiens (human)
Golgi membrane	Bile salt export pump	Homo sapiens (human)
endosome	Bile salt export pump	Homo sapiens (human)
plasma membrane	Bile salt export pump	Homo sapiens (human)
cell surface	Bile salt export pump	Homo sapiens (human)
apical plasma membrane	Bile salt export pump	Homo sapiens (human)
intercellular canaliculus	Bile salt export pump	Homo sapiens (human)
intracellular canaliculus	Bile salt export pump	Homo sapiens (human)
recycling endosome	Bile salt export pump	Homo sapiens (human)
recycling endosome membrane	Bile salt export pump	Homo sapiens (human)
extracellular exosome	Bile salt export pump	Homo sapiens (human)
membrane	Bile salt export pump	Homo sapiens (human)
extracellular space	Interferon beta	Homo sapiens (human)
extracellular region	Interferon beta	Homo sapiens (human)
Golgi membrane	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
endoplasmic reticulum	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
Golgi apparatus	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
plasma membrane	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
cell surface	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
ER to Golgi transport vesicle membrane	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
membrane	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
secretory granule membrane	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
phagocytic vesicle membrane	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
early endosome membrane	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
recycling endosome membrane	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
extracellular exosome	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
lumenal side of endoplasmic reticulum membrane	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
MHC class I protein complex	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
extracellular space	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
external side of plasma membrane	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
nucleus	Estrogen receptor	Homo sapiens (human)
nucleoplasm	Estrogen receptor	Homo sapiens (human)
transcription regulator complex	Estrogen receptor	Homo sapiens (human)
cytoplasm	Estrogen receptor	Homo sapiens (human)
Golgi apparatus	Estrogen receptor	Homo sapiens (human)
cytosol	Estrogen receptor	Homo sapiens (human)
plasma membrane	Estrogen receptor	Homo sapiens (human)
membrane	Estrogen receptor	Homo sapiens (human)
chromatin	Estrogen receptor	Homo sapiens (human)
euchromatin	Estrogen receptor	Homo sapiens (human)
protein-containing complex	Estrogen receptor	Homo sapiens (human)
nucleus	Estrogen receptor	Homo sapiens (human)
nuclear body	Cellular tumor antigen p53	Homo sapiens (human)
nucleus	Cellular tumor antigen p53	Homo sapiens (human)
nucleoplasm	Cellular tumor antigen p53	Homo sapiens (human)
replication fork	Cellular tumor antigen p53	Homo sapiens (human)
nucleolus	Cellular tumor antigen p53	Homo sapiens (human)
cytoplasm	Cellular tumor antigen p53	Homo sapiens (human)
mitochondrion	Cellular tumor antigen p53	Homo sapiens (human)
mitochondrial matrix	Cellular tumor antigen p53	Homo sapiens (human)
endoplasmic reticulum	Cellular tumor antigen p53	Homo sapiens (human)
centrosome	Cellular tumor antigen p53	Homo sapiens (human)
cytosol	Cellular tumor antigen p53	Homo sapiens (human)
nuclear matrix	Cellular tumor antigen p53	Homo sapiens (human)
PML body	Cellular tumor antigen p53	Homo sapiens (human)
transcription repressor complex	Cellular tumor antigen p53	Homo sapiens (human)
site of double-strand break	Cellular tumor antigen p53	Homo sapiens (human)
germ cell nucleus	Cellular tumor antigen p53	Homo sapiens (human)
chromatin	Cellular tumor antigen p53	Homo sapiens (human)
transcription regulator complex	Cellular tumor antigen p53	Homo sapiens (human)
protein-containing complex	Cellular tumor antigen p53	Homo sapiens (human)
plasma membrane	Progesterone receptor	Homo sapiens (human)
nucleoplasm	Progesterone receptor	Homo sapiens (human)
mitochondrial outer membrane	Progesterone receptor	Homo sapiens (human)
cytosol	Progesterone receptor	Homo sapiens (human)
chromatin	Progesterone receptor	Homo sapiens (human)
nucleus	Progesterone receptor	Homo sapiens (human)
extracellular region	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
extracellular space	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
nuclear envelope	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
nuclear envelope lumen	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
nucleoplasm	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
cytosol	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
nuclear matrix	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
nuclear membrane	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
secretory granule lumen	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
perinuclear region of cytoplasm	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
ficolin-1-rich granule lumen	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
nuclear envelope	Polyunsaturated fatty acid 5-lipoxygenase	Homo sapiens (human)
fibrillar center	Steroid hormone receptor ERR1	Homo sapiens (human)
nucleus	Steroid hormone receptor ERR1	Homo sapiens (human)
nucleoplasm	Steroid hormone receptor ERR1	Homo sapiens (human)
cytoplasm	Steroid hormone receptor ERR1	Homo sapiens (human)
microtubule cytoskeleton	Steroid hormone receptor ERR1	Homo sapiens (human)
intercellular bridge	Steroid hormone receptor ERR1	Homo sapiens (human)
chromatin	Steroid hormone receptor ERR1	Homo sapiens (human)
nucleus	Steroid hormone receptor ERR1	Homo sapiens (human)
plasma membrane	Glutamate receptor 2	Rattus norvegicus (Norway rat)
peroxisome	Bifunctional epoxide hydrolase 2	Homo sapiens (human)
peroxisomal matrix	Bifunctional epoxide hydrolase 2	Homo sapiens (human)
cytosol	Bifunctional epoxide hydrolase 2	Homo sapiens (human)
extracellular exosome	Bifunctional epoxide hydrolase 2	Homo sapiens (human)
peroxisome	Bifunctional epoxide hydrolase 2	Homo sapiens (human)
virion membrane	Spike glycoprotein	Severe acute respiratory syndrome-related coronavirus
fibrillar center	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
nucleoplasm	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
cytosol	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
nucleus	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
cytoplasm	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
nucleus	Estrogen receptor beta	Homo sapiens (human)
nucleoplasm	Estrogen receptor beta	Homo sapiens (human)
mitochondrion	Estrogen receptor beta	Homo sapiens (human)
intracellular membrane-bounded organelle	Estrogen receptor beta	Homo sapiens (human)
chromatin	Estrogen receptor beta	Homo sapiens (human)
nucleus	Estrogen receptor beta	Homo sapiens (human)
plasma membrane	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
cell surface	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
apical plasma membrane	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
intercellular canaliculus	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
apical plasma membrane	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
nucleoplasm	Bile acid receptor	Homo sapiens (human)
chromatin	Bile acid receptor	Homo sapiens (human)
euchromatin	Bile acid receptor	Homo sapiens (human)
receptor complex	Bile acid receptor	Homo sapiens (human)
RNA polymerase II transcription regulator complex	Bile acid receptor	Homo sapiens (human)
nucleus	Bile acid receptor	Homo sapiens (human)
nucleus	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
mitochondrion	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
mitochondrial intermembrane space	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
mitochondrial matrix	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
cytosol	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
mitochondrial matrix	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (430)

Assay ID	Title	Year	Journal	Article
AID504810	Antagonists of the Thyroid Stimulating Hormone Receptor: HTS campaign	2010	Endocrinology, Jul, Volume: 151, Issue:7	A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID1347057	CD47-SIRPalpha protein protein interaction - LANCE assay qHTS validation	2019	PloS one, , Volume: 14, Issue:7	Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1347082	qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: LASV Primary Screen - GLuc reporter signal	2020	Antiviral research, 01, Volume: 173	A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347045	Natriuretic polypeptide receptor (hNpr1) antagonism - Pilot counterscreen GloSensor control cell line	2019	Science translational medicine, 07-10, Volume: 11, Issue:500	Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID504836	Inducers of the Endoplasmic Reticulum Stress Response (ERSR) in human glioma: Validation	2002	The Journal of biological chemistry, Apr-19, Volume: 277, Issue:16	Sustained ER Ca2+ depletion suppresses protein synthesis and induces activation-enhanced cell death in mast cells.
AID1347410	qHTS for inhibitors of adenylyl cyclases using a fission yeast platform: a pilot screen against the NCATS LOPAC library	2019	Cellular signalling, 08, Volume: 60	A fission yeast platform for heterologous expression of mammalian adenylyl cyclases and high throughput screening.
AID1347058	CD47-SIRPalpha protein protein interaction - HTRF assay qHTS validation	2019	PloS one, , Volume: 14, Issue:7	Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID588349	qHTS for Inhibitors of ATXN expression: Validation of Cytotoxic Assay
AID1347050	Natriuretic polypeptide receptor (hNpr2) antagonism - Pilot subtype selectivity assay	2019	Science translational medicine, 07-10, Volume: 11, Issue:500	Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID1347151	Optimization of GU AMC qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay	2020	Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49	Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347405	qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS LOPAC collection	2020	ACS chemical biology, 07-17, Volume: 15, Issue:7	High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1347083	qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: Viability assay - alamar blue signal for LASV Primary Screen	2020	Antiviral research, 01, Volume: 173	A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347049	Natriuretic polypeptide receptor (hNpr1) antagonism - Pilot screen	2019	Science translational medicine, 07-10, Volume: 11, Issue:500	Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID1508630	Primary qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome: Secreted ER Calcium Modulated Protein (SERCaMP) assay	2021	Cell reports, 04-27, Volume: 35, Issue:4	A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome.
AID1347059	CD47-SIRPalpha protein protein interaction - Alpha assay qHTS validation	2019	PloS one, , Volume: 14, Issue:7	Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID588378	qHTS for Inhibitors of ATXN expression: Validation
AID1347086	qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lymphocytic Choriomeningitis Arenaviruses (LCMV): LCMV Primary Screen - GLuc reporter signal	2020	Antiviral research, 01, Volume: 173	A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID504812	Inverse Agonists of the Thyroid Stimulating Hormone Receptor: HTS campaign	2010	Endocrinology, Jul, Volume: 151, Issue:7	A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID468388	Antagonist activity at estrogen receptor in human Ishikawa cells assessed as inhibition of ERE-dependent alkaline phosphatase levels at 1 uM	2009	Journal of medicinal chemistry, Nov-12, Volume: 52, Issue:21	Novel dehydroepiandrosterone derivatives with antiapoptotic, neuroprotective activity.
AID1594513	Selective estrogen receptor down-regulator activity at FLAG-tagged ERalpha (unknown origin) expressed in HEK293 cells assessed as induction of ERalpha degradation by measuring rate constant for degradation by luciferase reporter gene assay relative to unt	2019	Bioorganic & medicinal chemistry, 05-15, Volume: 27, Issue:10	Structure-activity relationship study of estrogen receptor down-regulators with a diphenylmethane skeleton.
AID1616741	Inhibition of bacterial Beta-lactamase TEM-1 M182T/G238S mutant pre-incubated for 5 mins before addition of chromogenic beta-lactamase substrate CENTA by spectrophotometry	2019	Journal of medicinal chemistry, 11-14, Volume: 62, Issue:21	Protein Stability Effects in Aggregate-Based Enzyme Inhibition.
AID473608	Down regulation of ERalpha expression in human MCF7 cell whole cell extract at 1 uM after 16 hrs by Western blotting	2010	Journal of medicinal chemistry, Apr-22, Volume: 53, Issue:8	Characterization of the pharmacophore properties of novel selective estrogen receptor downregulators (SERDs).
AID469732	Antagonist activity at estrogen receptor beta ligand binding domain expressed in african green monkey COS7 cells co-transfected with Gal4-LBD by luciferase reporter gene assay	2009	Journal of natural products, Nov, Volume: 72, Issue:11	The lecanindoles, nonsteroidal progestins from the terrestrial fungus Verticillium lecanii 6144.
AID1811378	Induction of human ishikawa cells proliferation at 300 nM measured after 48 hrs by CCK8 assay	2021	European journal of medicinal chemistry, Dec-15, Volume: 226	Development of novel tetrahydroisoquinoline-hydroxamate conjugates as potent dual SERDs/HDAC inhibitors for the treatment of breast cancer.
AID1629296	Displacement of fluoromone ligand from recombinant ER-alpha (unknown origin) by LanthaScreen TR-FRET assay	2016	Journal of medicinal chemistry, 09-08, Volume: 59, Issue:17	Fulvestrant-3 Boronic Acid (ZB716): An Orally Bioavailable Selective Estrogen Receptor Downregulator (SERD).
AID1228237	Displacement of [3H]-E2 from estrogen receptor-beta (unknown origin) by scintillation counting analysis	2015	Journal of medicinal chemistry, Jun-25, Volume: 58, Issue:12	Identification of GDC-0810 (ARN-810), an Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts.
AID1559007	Cytotoxicity against human T47D monolayer cells assessed as reduction in tumor cell viability at 10 nM incubated for 10 days by celltiter-glo 3D cell viability assay	2019	Journal of medicinal chemistry, 12-26, Volume: 62, Issue:24	Design and Synthesis of Basic Selective Estrogen Receptor Degraders for Endocrine Therapy Resistant Breast Cancer.
AID249001	Inhibition of 10e-9 M E2 stimulated transcriptional activation in ER+MCF-7/2a breast cancer cells	2004	Bioorganic & medicinal chemistry letters, Sep-20, Volume: 14, Issue:18	Synthesis and biological evaluation of stilbene-based pure estrogen antagonists.
AID1387901	Downregulation of estrogen receptor beta protein levels in human MCF7 cell lysate at 1 uM after 24 hrs by Western blot analysis	2018	Journal of medicinal chemistry, 01-25, Volume: 61, Issue:2	Lead Optimization of Benzoxepin-Type Selective Estrogen Receptor (ER) Modulators and Downregulators with Subtype-Specific ERα and ERβ Activity.
AID503305	Antiproliferative activity against human PC3 cells at 500 nM after 120 hrs by MTT assay relative to DMSO	2006	Nature chemical biology, Jun, Volume: 2, Issue:6	Identifying off-target effects and hidden phenotypes of drugs in human cells.
AID1829689	Induction of ERalpha degradation in human MCF7 cells at 1 uM incubated for 72 hrs by Western immuno assay relative to control
AID1602147	Antitumor activity against mouse EAC cells implanted in Swiss albino mouse assessed as reduction in tumor size at 5 mg/mouse, ip dosed once weekly starting 5 days after inoculation	2019	European journal of medicinal chemistry, Mar-15, Volume: 166	Structure-based drug design, synthesis, In vitro, and In vivo biological evaluation of indole-based biomimetic analogs targeting estrogen receptor-α inhibition.
AID1829675	Antagonist activity at ERalpha (unknown origin) expressed in human U2OS cells assessed as inhibition of E2-induced transactivation by dual luciferase reporter gene assay
AID1155384	Inhibition of 17beta-estradiol-induced in ERalpha positive human MCF7 cells proliferation assessed as [3H]-thymidine incorporation at 10 nM after 72 hrs by liquid scintillation counting	2014	European journal of medicinal chemistry, Jul-23, Volume: 82	Synthesis and biological evaluation of salpichrolide analogs as antiestrogenic agents.
AID625279	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for bilirubinemia	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625283	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for elevated liver function tests	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1469726	Induction of selective estrogen receptor alpha degradation in human MCF7 cells at 10 uM after 24 hrs by Western blot analysis	2018	Journal of medicinal chemistry, 04-12, Volume: 61, Issue:7	Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen Receptor Positive Breast Cancer.
AID625289	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver disease	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1283273	Decrease in cholesterol levels in human SLOS fibroblasts at 10 nM after 5 days by LC-MS/GC-MS analysis	2016	Journal of medicinal chemistry, Feb-11, Volume: 59, Issue:3	The Effect of Small Molecules on Sterol Homeostasis: Measuring 7-Dehydrocholesterol in Dhcr7-Deficient Neuro2a Cells and Human Fibroblasts.
AID69065	Relative Binding Affinity for estrogen receptor in Human Breast cancer or normal uterine cytosol in 2.5%DMF compared to estradiol	1997	Journal of medicinal chemistry, Jul-04, Volume: 40, Issue:14	(S)-(+)-4-[7-(2,2-dimethyl-1-oxopropoxy)-4-methyl-2-[4-[2-(1-piperidinyl)-ethoxy]phenyl]-2H-1-benzopyran-3-yl]-phenyl 2,2-dimethylpropanoate (EM-800): a highly potent, specific, and orally active nonsteroidal antiestrogen.
AID69066	Relative Binding Affinity for estrogen receptor in Human Breast cancer or normal uterine cytosol in 2.5%DMF compared to estradiol	1997	Journal of medicinal chemistry, Jul-04, Volume: 40, Issue:14	(S)-(+)-4-[7-(2,2-dimethyl-1-oxopropoxy)-4-methyl-2-[4-[2-(1-piperidinyl)-ethoxy]phenyl]-2H-1-benzopyran-3-yl]-phenyl 2,2-dimethylpropanoate (EM-800): a highly potent, specific, and orally active nonsteroidal antiestrogen.
AID1891538	Antitumor activity against tamoxifen-resistant human MCF7 cells xenografted in mouse assessed as tumor growth inhibition at 3 mg, po dosed once daily for 21 days relative to control	2022	Bioorganic & medicinal chemistry letters, 06-15, Volume: 66	Discovery and preclinical profile of LX-039, a novel indole-based oral selective estrogen receptor degrader (SERD).
AID473606	Down regulation of ERalpha expression in human MCF7 cell matrix fraction at 1 uM after 16 hrs by Western blotting	2010	Journal of medicinal chemistry, Apr-22, Volume: 53, Issue:8	Characterization of the pharmacophore properties of novel selective estrogen receptor downregulators (SERDs).
AID1768137	Total clearance in Sprague-Dawley rat at 1 mg/kg, iv or po measured after 0.033 to 24 hrs by LC/MS/MS analysis
AID1572951	Induction of ERalpha degradation in in human MCF7 cells assessed as reduction in ER protein level at 30 nM after 24 hrs by Western blot analysis relative to control	2019	Journal of medicinal chemistry, 02-14, Volume: 62, Issue:3	Discovery of ERD-308 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Estrogen Receptor (ER).
AID1768140	Induction of estrogen receptor degradation in human MCF7 cells at 0.0002 to 100 nM incubated for 4 hrs by Alexafluor-488 conjugate anti-mouse IgG staining based fluorescence method relative to control
AID1228241	Induction of estrogen receptor-alpha degradation in human MCF7 cells at 1 uM after 20 hrs by Western blot analysis	2015	Journal of medicinal chemistry, Jun-25, Volume: 58, Issue:12	Identification of GDC-0810 (ARN-810), an Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts.
AID70645	Displacement of [3H]17-beta-estradiol from human Estrogen receptor beta	2000	Bioorganic & medicinal chemistry letters, Jan-17, Volume: 10, Issue:2	Synthesis and estrogenic activities of novel 7-thiosubstituted estratriene derivatives.
AID1681457	Agonist activity at ERalpha in human MCF7 cells assessed as increase in TFF1 mRNA expression level at 100 nM measured after 24 hrs	2020	Journal of medicinal chemistry, 12-10, Volume: 63, Issue:23	Discovery of AZD9833, a Potent and Orally Bioavailable Selective Estrogen Receptor Degrader and Antagonist.
AID597266	Antiproliferative activity against estrogen receptor-deficient human NCI-ADR-RES cells incubated with 0.003 nM of estradiol and 0.01 nM of testosterone after 48 hrs by sulforhodamine B assay in presence of 5% fetal bovine serum	2011	Journal of medicinal chemistry, May-26, Volume: 54, Issue:10	Biomimetic syntheses and antiproliferative activities of racemic, natural (-), and unnnatural (+) glyceollin I.
AID625292	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) combined score	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1594506	Binding affinity to GST-tagged human ER alpha ligand-binding domain by TR-FRET assay	2019	Bioorganic & medicinal chemistry, 05-15, Volume: 27, Issue:10	Structure-activity relationship study of estrogen receptor down-regulators with a diphenylmethane skeleton.
AID1469719	Induction of selective estrogen receptor alpha degradation in human MCF7 cells after 18 to 24 hrs by in-cell Western analysis	2018	Journal of medicinal chemistry, 04-12, Volume: 61, Issue:7	Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen Receptor Positive Breast Cancer.
AID1768139	Induction of estrogen receptor degradation in human MCF7 cells incubated for 4 hrs by Alexafluor -488 conjugate anti-mouse IgG staining based fluorescence method
AID248483	Inhibition of ER-MDA-MB 231 breast cancer cell proliferation over 200 hr	2004	Bioorganic & medicinal chemistry letters, Sep-20, Volume: 14, Issue:18	Synthesis and biological evaluation of stilbene-based pure estrogen antagonists.
AID1473741	Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	2013	Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1	A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID1155379	Inhibition of 17beta-estradiol-induced in ERalpha positive human MCF7 cells proliferation assessed as [3H]-thymidine incorporation after 72 hrs by liquid scintillation counting	2014	European journal of medicinal chemistry, Jul-23, Volume: 82	Synthesis and biological evaluation of salpichrolide analogs as antiestrogenic agents.
AID1811367	Antiproliferative activity against human MCF7 cells assessed as reduction in cell growth measured after 6 days by WST8 assay	2021	European journal of medicinal chemistry, Dec-15, Volume: 226	Development of novel tetrahydroisoquinoline-hydroxamate conjugates as potent dual SERDs/HDAC inhibitors for the treatment of breast cancer.
AID1768143	Intrinsic clearance in human hepatocytes measured up to 60 mins by LC/MS/MS analysis
AID1251781	Antagonist activity at ERalpha receptor in human MCF7 cells	2015	Journal of medicinal chemistry, Oct-22, Volume: 58, Issue:20	Optimization of a Novel Binding Motif to (E)-3-(3,5-Difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic Acid (AZD9496), a Potent and Orally Bioavailable Selective Estrogen Receptor Downregu
AID239838	Relative binding affinity for Estrogen receptor of Calf uterine cytosol	2004	Bioorganic & medicinal chemistry letters, Sep-20, Volume: 14, Issue:18	Synthesis and biological evaluation of stilbene-based pure estrogen antagonists.
AID1251783	Antagonist activity at progesterone receptor in human MCF cells assessed as estradiol-induced receptor response	2015	Journal of medicinal chemistry, Oct-22, Volume: 58, Issue:20	Optimization of a Novel Binding Motif to (E)-3-(3,5-Difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic Acid (AZD9496), a Potent and Orally Bioavailable Selective Estrogen Receptor Downregu
AID1658827	Antiproliferative activity against human MCF7 cells assessed as reduction in cell viability after 72 hrs by Celltiter-Glo assay	2020	ACS medicinal chemistry letters, Jun-11, Volume: 11, Issue:6	Discovery of GNE-149 as a Full Antagonist and Efficient Degrader of Estrogen Receptor alpha for ER+ Breast Cancer.
AID1356853	Reduction in uterine wet weight in ethynyl estradiol-stimulated CD-IGS rat at 200 mg/kg, po dosed daily for 3 days by gavage followed 15 mins later by 0.1 mg/kg, po ethynyl estradiol and measured 24 hrs after last dose by immature rat uterine wet weight a	2018	Journal of medicinal chemistry, 09-13, Volume: 61, Issue:17	Identification of an Orally Bioavailable Chromene-Based Selective Estrogen Receptor Degrader (SERD) That Demonstrates Robust Activity in a Model of Tamoxifen-Resistant Breast Cancer.
AID1443610	Induction of ERalpha degradation in human MCF7 cells after 18 hrs by Western blot analysis	2017	Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7	Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ERα+ Breast Cancer.
AID306821	Agonist activity at human ERalpha in T47D cells assessed as enhancement of AP1-driven transactivation at 5 uM by luciferase reporter assay relative to DMSO	2007	Bioorganic & medicinal chemistry letters, May-01, Volume: 17, Issue:9	Identification of a series of tetrahydroisoquinoline derivatives as potential therapeutic agents for breast cancer.
AID1681453	Induction of ERalpha degradation in human MCF7 cells incubated for 48 hrs by Western blot analysis	2020	Journal of medicinal chemistry, 12-10, Volume: 63, Issue:23	Discovery of AZD9833, a Potent and Orally Bioavailable Selective Estrogen Receptor Degrader and Antagonist.
AID1443580	Antitumor activity against human MCF7 cells xenografted in 17-beta estradiol release pellet implanted immunocompromised nude mouse assessed as tumor growth inhibition at 250 mg/kg, sc administered once per week measured on day 108 relative to control	2017	Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7	Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ERα+ Breast Cancer.
AID1469717	Induction of selective estrogen receptor alpha degradation in human MCF7 cells harboring TK-ERE-Luc assessed as reduction in estradiol-induced transcriptional activity after 24 hrs by luciferase reporter gene assay	2018	Journal of medicinal chemistry, 04-12, Volume: 61, Issue:7	Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen Receptor Positive Breast Cancer.
AID1658826	Induction of ERalpha degradation in human MCF7 cells after 4 hrs by FITC/Hoechst staining based immunofluorescence imaging analysis relative to 5 nM fulvestrant	2020	ACS medicinal chemistry letters, Jun-11, Volume: 11, Issue:6	Discovery of GNE-149 as a Full Antagonist and Efficient Degrader of Estrogen Receptor alpha for ER+ Breast Cancer.
AID304032	Inhibition of 30 nM estradiol induced stimulation of DNA synthesis in human 320DM cells assessed as ratio of treated to untreated control at 1.1 uM after 48 hrs by [3H]thymidine incorporation assay	2007	Journal of medicinal chemistry, Dec-13, Volume: 50, Issue:25	Synthesis and evaluation of the antiproliferative activities of derivatives of carboxyalkyl isoflavones linked to N-t-Boc-hexylenediamine.
AID1558990	Antiproliferative activity against human MCF7:WS8 cells assessed as reduction in cell viability incubated for 5 days by Hoechst 33258 dye based assay relative to control	2019	Journal of medicinal chemistry, 12-26, Volume: 62, Issue:24	Design and Synthesis of Basic Selective Estrogen Receptor Degraders for Endocrine Therapy Resistant Breast Cancer.
AID269788	AUC in Sprague-Dawley rat at 10 mg/kg, iv	2006	Bioorganic & medicinal chemistry letters, Aug-01, Volume: 16, Issue:15	Discovery of thiochroman derivatives bearing a carboxy-containing side chain as orally active pure antiestrogens.
AID297565	Binding affinity to human ERbeta	2007	Journal of medicinal chemistry, Sep-06, Volume: 50, Issue:18	Design, synthesis, and estrogenic activity of a novel estrogen receptor modulator--a hybrid structure of 17beta-estradiol and vitamin E in hippocampal neurons.
AID1446060	Downregulation of ERalpha in human MCF-7 cells assessed as reduction of estradiol-induced pS2 mRNA levels at 3 x 10'-9 M, 3 x 10'-8 M, 3 x 10'-7 M, 3 x 10'-6 M after 24 hrs by RT-PCR method	2017	Journal of medicinal chemistry, 07-27, Volume: 60, Issue:14	Adamantyl Antiestrogens with Novel Side Chains Reveal a Spectrum of Activities in Suppressing Estrogen Receptor Mediated Activities in Breast Cancer Cells.
AID1616743	Inhibition of bacterial Beta-lactamase TEM-1 R164S mutant pre-incubated for 5 mins before addition of chromogenic beta-lactamase substrate CENTA by spectrophotometry	2019	Journal of medicinal chemistry, 11-14, Volume: 62, Issue:21	Protein Stability Effects in Aggregate-Based Enzyme Inhibition.
AID304034	Inhibition of 300 nM estradiol induced stimulation of DNA synthesis in human 320DM cells assessed as ratio of treated to untreated control at 1.1 uM after 48 hrs by [3H]thymidine incorporation assay	2007	Journal of medicinal chemistry, Dec-13, Volume: 50, Issue:25	Synthesis and evaluation of the antiproliferative activities of derivatives of carboxyalkyl isoflavones linked to N-t-Boc-hexylenediamine.
AID243059	Ratio of inhibitory activity against human estrogen receptors 2 and 1	2005	Bioorganic & medicinal chemistry letters, Sep-01, Volume: 15, Issue:17	Estrogen receptor ligands. Part 13: Dihydrobenzoxathiin SERAMs with an optimized antagonist side chain.
AID1629302	Half life in C57BL/6 mouse at 8.3 mg/kg, sc by HPLC-MS/MS analysis	2016	Journal of medicinal chemistry, 09-08, Volume: 59, Issue:17	Fulvestrant-3 Boronic Acid (ZB716): An Orally Bioavailable Selective Estrogen Receptor Downregulator (SERD).
AID1811384	Stability in human liver microsomes assessed as intrinsic clearance	2021	European journal of medicinal chemistry, Dec-15, Volume: 226	Development of novel tetrahydroisoquinoline-hydroxamate conjugates as potent dual SERDs/HDAC inhibitors for the treatment of breast cancer.
AID1443553	Induction of ERalpha degradation in human MCF7 cells after 18 to 24 hrs by Western blot analysis	2017	Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7	Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ERα+ Breast Cancer.
AID271230	Antagonist effect on estrogen activity assessed as inhibition of estrogen-stimulated uterine weight gain in ovariectomized mouse at 3 mg/kg, po	2006	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 16, Issue:18	Newly discovered orally active pure antiestrogens.
AID368185	Down regulation of estrogen receptor alpha expression in human MCF7 cells after 24 hrs by Western blot analysis	2009	Journal of medicinal chemistry, Feb-12, Volume: 52, Issue:3	Effect of fluorination on the pharmacological profile of 11beta isomers of fulvestrant in breast carcinoma cells.
AID1558989	Antiproliferative activity against human MCF7:WS8 cells assessed as reduction in cell viability incubated for 5 days by Hoechst 33258 dye based assay	2019	Journal of medicinal chemistry, 12-26, Volume: 62, Issue:24	Design and Synthesis of Basic Selective Estrogen Receptor Degraders for Endocrine Therapy Resistant Breast Cancer.
AID1829679	Antiproliferative activity against human ER-positive MCF7 cells assessed as reduction in cell viability measured after 120 hrs by crystal violet staining based assay
AID1446058	Downregulation of ERalpha in human MCF-7 cells assessed as reduction of estradiol-induced GREB1 mRNA levels at 3 x 10'-9 M, 3 x 10'-8 M, 3 x 10'-7 M, 3 x 10'-6 M after 24 hrs by RT-PCR method	2017	Journal of medicinal chemistry, 07-27, Volume: 60, Issue:14	Adamantyl Antiestrogens with Novel Side Chains Reveal a Spectrum of Activities in Suppressing Estrogen Receptor Mediated Activities in Breast Cancer Cells.
AID597275	Antiproliferative activity against androgen receptor-deficient human PC3 cells incubated with 0.6 nM of estradiol and 0.7 nM of testosterone after 48 hrs by sulforhodamine B assay	2011	Journal of medicinal chemistry, May-26, Volume: 54, Issue:10	Biomimetic syntheses and antiproliferative activities of racemic, natural (-), and unnnatural (+) glyceollin I.
AID1228236	Displacement of [3H]-E2 from estrogen receptor-alpha (unknown origin) by scintillation counting analysis	2015	Journal of medicinal chemistry, Jun-25, Volume: 58, Issue:12	Identification of GDC-0810 (ARN-810), an Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts.
AID1558987	Antiproliferative activity against human MCF7:5C cells assessed as reduction in cell viability incubated for 7 days by Hoechst 33258 dye based assay	2019	Journal of medicinal chemistry, 12-26, Volume: 62, Issue:24	Design and Synthesis of Basic Selective Estrogen Receptor Degraders for Endocrine Therapy Resistant Breast Cancer.
AID597274	Antiproliferative activity against estrogen receptor-deficient human MCF12A cells incubated with 100 nM of estradiol and 0.07 nM of testosterone after 48 hrs by sulforhodamine B assay in presence of fetal bovine serum and NuSerum	2011	Journal of medicinal chemistry, May-26, Volume: 54, Issue:10	Biomimetic syntheses and antiproliferative activities of racemic, natural (-), and unnnatural (+) glyceollin I.
AID368180	Antiestrogenic activity at human recombinant estrogen receptor alpha assessed as inhibition of recruitment of LxxLL-containing coactivators after 30 mins by ELISA in presence of estradiol	2009	Journal of medicinal chemistry, Feb-12, Volume: 52, Issue:3	Effect of fluorination on the pharmacological profile of 11beta isomers of fulvestrant in breast carcinoma cells.
AID1901456	Anticancer activity against human MCF7 cells assessed as reduction in cell viability incubated for 24 hrs in presence of 10% CD-FBS by alamar blue assay	2022	Journal of medicinal chemistry, 03-10, Volume: 65, Issue:5	Activators of the Anticipatory Unfolded Protein Response with Enhanced Selectivity for Estrogen Receptor Positive Breast Cancer.
AID306822	Antagonist activity at human PR in T47D cells assessed as MMTV-driven transactivation at 5 uM by luciferase reporter assay relative to progesterone	2007	Bioorganic & medicinal chemistry letters, May-01, Volume: 17, Issue:9	Identification of a series of tetrahydroisoquinoline derivatives as potential therapeutic agents for breast cancer.
AID1768203	Antiproliferative activity against human T47D incubated for 7 to 10 days by celltiter-glo luminescent cell viability assay
AID597269	Antiproliferative activity against estrogen receptor-deficient human NCI-ADR-RES cells incubated with 0.06 nM of estradiol and 0.07 nM of testosterone after 48 hrs by sulforhodamine B assay in presence of fetal bovine serum and NuSerum	2011	Journal of medicinal chemistry, May-26, Volume: 54, Issue:10	Biomimetic syntheses and antiproliferative activities of racemic, natural (-), and unnnatural (+) glyceollin I.
AID625280	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholecystitis	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1768149	Distribution coefficient, logD of the compound at pH 7.4
AID1772292	Antitumor activity against human MCF7 cells xenografted in CD1 mouse assessed as tumor growth inhibition at 3 mg/kg, sc administered once daily for 28 days by caliper method	2021	Journal of medicinal chemistry, 04-22, Volume: 64, Issue:8	Bispecific Estrogen Receptor α Degraders Incorporating Novel Binders Identified Using DNA-Encoded Chemical Library Screening.
AID1652275	Growth inhibition of fulvestrant-resistant human MCF7:CFR 3D spheroid cells at 100 nM supplemented with fresh medium containing compound every 2 to 3 days for 9 days by celltitre-glo assay relative to control	2020	Journal of medicinal chemistry, 07-09, Volume: 63, Issue:13	Novel Pyrrolopyridone Bromodomain and Extra-Terminal Motif (BET) Inhibitors Effective in Endocrine-Resistant ER+ Breast Cancer with Acquired Resistance to Fulvestrant and Palbociclib.
AID1829672	Aqueous solubility of the compound
AID1658837	Agonist activity at ERalpha in human Ishikawa cells after 72 hrs by alkaline phosphatase assay	2020	ACS medicinal chemistry letters, Jun-11, Volume: 11, Issue:6	Discovery of GNE-149 as a Full Antagonist and Efficient Degrader of Estrogen Receptor alpha for ER+ Breast Cancer.
AID1829663	Displacement of fluorescent-labeled E2 from LBD of ERalpha (unknown origin) by TR-FRET assay
AID69068	Relative affinity for estrogen receptor of Human Breast cancer or normal uterine cytosol (3.3%ethanol) compared to estradiol	1997	Journal of medicinal chemistry, Jul-04, Volume: 40, Issue:14	(S)-(+)-4-[7-(2,2-dimethyl-1-oxopropoxy)-4-methyl-2-[4-[2-(1-piperidinyl)-ethoxy]phenyl]-2H-1-benzopyran-3-yl]-phenyl 2,2-dimethylpropanoate (EM-800): a highly potent, specific, and orally active nonsteroidal antiestrogen.
AID1283262	Inhibition of DR24 in human SLOS fibroblasts assessed as decrease in 7-DHC levels at 10 nM after 5 days by LC-MS/GC-MS analysis	2016	Journal of medicinal chemistry, Feb-11, Volume: 59, Issue:3	The Effect of Small Molecules on Sterol Homeostasis: Measuring 7-Dehydrocholesterol in Dhcr7-Deficient Neuro2a Cells and Human Fibroblasts.
AID1572960	Induction ERalpha degradation in human MCF7 cells assessed as suppression of GREB1 mRNA levels up to 300 nM by qRT-PCR analysis	2019	Journal of medicinal chemistry, 02-14, Volume: 62, Issue:3	Discovery of ERD-308 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Estrogen Receptor (ER).
AID1559008	Cytotoxicity against human T47D monolayer cells harboring Y537S mutant assessed as reduction in tumor cell viability at 10 nM incubated for 10 days by celltiter-glo 3D cell viability assay	2019	Journal of medicinal chemistry, 12-26, Volume: 62, Issue:24	Design and Synthesis of Basic Selective Estrogen Receptor Degraders for Endocrine Therapy Resistant Breast Cancer.
AID1469734	Antitumor activity against human MCF7 cells xenografted in NOD SCID gamma mouse assessed as change in tumor volume at 5 mg, sc administered once in a week for 48 days post tumor implantation measured 7 hrs post last dose	2018	Journal of medicinal chemistry, 04-12, Volume: 61, Issue:7	Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen Receptor Positive Breast Cancer.
AID1658830	Induction of ERalpha degradation in human T47D cells relative to control	2020	ACS medicinal chemistry letters, Jun-11, Volume: 11, Issue:6	Discovery of GNE-149 as a Full Antagonist and Efficient Degrader of Estrogen Receptor alpha for ER+ Breast Cancer.
AID70002	In vitro displacement of 0.5 nM [3H]17-beta-estradiol from human Estrogen receptor alpha	2003	Journal of medicinal chemistry, Apr-10, Volume: 46, Issue:8	De novo design, synthesis, and evaluation of novel nonsteroidal phenanthrene ligands for the estrogen receptor.
AID1690959	Displacement of fluorescent-labelled E2 from recombinant human GST-tagged ERbeta by LanthaScreen TR-FRET assay relative to E2	2020	European journal of medicinal chemistry, Apr-15, Volume: 192	Development of bivalent triarylalkene- and cyclofenil-derived dual estrogen receptor antagonists and downregulators.
AID597267	Antiproliferative activity against human MCF7 cells expressing estrogen receptor incubated with 0.06 nM of estradiol and 0.07 nM of testosterone after 48 hrs by sulforhodamine B assay in presence of fetal bovine serum and NuSerum	2011	Journal of medicinal chemistry, May-26, Volume: 54, Issue:10	Biomimetic syntheses and antiproliferative activities of racemic, natural (-), and unnnatural (+) glyceollin I.
AID1535224	Induction of ERalpha degradation in human MCF7 cells in phenol red free RPMI medium containing 5% charcoal-stripped FBS incubated for 4 hrs by IRDye 800CW/DRAQ5 dye based in-cell Western assay	2019	Bioorganic & medicinal chemistry letters, 02-01, Volume: 29, Issue:3	Selective estrogen receptor degraders with novel structural motifs induce regression in a tamoxifen-resistant breast cancer xenograft.
AID304029	Inhibition of DNA synthesis in human MLS cells assessed as ratio of treated to untreated control at 1.1 uM after 48 hrs by [3H]thymidine incorporation assay	2007	Journal of medicinal chemistry, Dec-13, Volume: 50, Issue:25	Synthesis and evaluation of the antiproliferative activities of derivatives of carboxyalkyl isoflavones linked to N-t-Boc-hexylenediamine.
AID468984	Inhibition of human 17beta-HSD7 expressed in HEK293 cells assessed as inhibition of reduction of [14C]estrone into [14C]estradiol at 0.3 uM after 7 hrs	2009	Journal of medicinal chemistry, Dec-10, Volume: 52, Issue:23	Potent and selective steroidal inhibitors of 17beta-hydroxysteroid dehydrogenase type 7, an enzyme that catalyzes the reduction of the key hormones estrone and dihydrotestosterone.
AID1572959	Induction ERalpha degradation in human MCF7 cells assessed as suppression of pGR mRNA levels up to 300 nM by qRT-PCR analysis	2019	Journal of medicinal chemistry, 02-14, Volume: 62, Issue:3	Discovery of ERD-308 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Estrogen Receptor (ER).
AID1565145	Induction of ERalpha degradation in human MCF7 cells assessed as decrease in ERalpha protein expression at 5 uM incubated for 24 hrs by Western blot analysis relative to control	2019	European journal of medicinal chemistry, Nov-15, Volume: 182	Novel class of 7-Oxabicyclo[2.2.1]heptene sulfonamides with long alkyl chains displaying improved estrogen receptor α degradation activity.
AID1572966	Induction of ERalpha degradation in human MCF7 cells assessed as effect on ER protein/GADPH ratio at 10 nM after 4 hrs by Western blot analysis relative to control	2019	Journal of medicinal chemistry, 02-14, Volume: 62, Issue:3	Discovery of ERD-308 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Estrogen Receptor (ER).
AID1690981	Selectivity index, ratio of IC50 for cytotoxicity against African green monkey COS7 cells to IC50 for antiproliferative activity against human MCF7 cells	2020	European journal of medicinal chemistry, Apr-15, Volume: 192	Development of bivalent triarylalkene- and cyclofenil-derived dual estrogen receptor antagonists and downregulators.
AID625281	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholelithiasis	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID427280	Growth inhibition of human MCF7 cells at 1 uM after 4 days by MTT assay	2009	Bioorganic & medicinal chemistry, Jul-01, Volume: 17, Issue:13	9,11-Secosterols with antiproliferative activity from the gorgonian Eunicella cavolini.
AID1443577	Induction of ERalpha degradation in human MCF7 cells assessed as inhibition of insulin-mediated cell proliferation after 6 days by Hoechst 33258 dye-based assay	2017	Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7	Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ERα+ Breast Cancer.
AID1469727	Induction of selective estrogen receptor alpha degradation in human MCF7 cells at 10 uM after 24 hrs in presence of proteasome inhibitor MG132 by Western blot analysis	2018	Journal of medicinal chemistry, 04-12, Volume: 61, Issue:7	Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen Receptor Positive Breast Cancer.
AID1469729	Induction of selective estrogen receptor alpha degradation in human MCF7 cells harboring TK-ERE-Luc assessed as reduction in estradiol-induced GREB1 mRNA expression after 24 hrs by TaqMan assay	2018	Journal of medicinal chemistry, 04-12, Volume: 61, Issue:7	Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen Receptor Positive Breast Cancer.
AID1772267	Induction of ERalpha degradation in human MCF7 cells assessed as reduction in ERalpha expression at 1 uM after 4 hrs by Western blotting analysis	2021	Journal of medicinal chemistry, 04-22, Volume: 64, Issue:8	Bispecific Estrogen Receptor α Degraders Incorporating Novel Binders Identified Using DNA-Encoded Chemical Library Screening.
AID1559010	Induction of degradation of ERalpha in human MCF7:WS8 cells at 10 nM in presence of MG-132 incubated for 24 hrs by Western blot analysis	2019	Journal of medicinal chemistry, 12-26, Volume: 62, Issue:24	Design and Synthesis of Basic Selective Estrogen Receptor Degraders for Endocrine Therapy Resistant Breast Cancer.
AID1690979	Antiproliferative activity against human MCF7 cells assessed as reduction in cell mass measured after 72 hrs by crystal violet staining based assay	2020	European journal of medicinal chemistry, Apr-15, Volume: 192	Development of bivalent triarylalkene- and cyclofenil-derived dual estrogen receptor antagonists and downregulators.
AID68904	Apparent inhibition constant for estrogen receptor in Human Breast cancer cytosol in 2.5%DMF	1997	Journal of medicinal chemistry, Jul-04, Volume: 40, Issue:14	(S)-(+)-4-[7-(2,2-dimethyl-1-oxopropoxy)-4-methyl-2-[4-[2-(1-piperidinyl)-ethoxy]phenyl]-2H-1-benzopyran-3-yl]-phenyl 2,2-dimethylpropanoate (EM-800): a highly potent, specific, and orally active nonsteroidal antiestrogen.
AID1512336	Induction of VHL E3 ligase mediated ERalpha degradation in human MCF7 cells at 0.3 uM by cell-based immunofluorescence assay	2019	ACS medicinal chemistry letters, Oct-10, Volume: 10, Issue:10	PROTAC-Mediated Degradation of Estrogen Receptor in the Treatment of Cancer.
AID1474166	Liver toxicity in human assessed as induction of drug-induced liver injury by measuring severity class index	2016	Drug discovery today, Apr, Volume: 21, Issue:4	DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID1506573	Downregulation of ERalpha expression in human MCF7 cells at 0.1 uM after 6 hrs by Western blot method relative to beta-actin	2017	MedChemComm, Jan-01, Volume: 8, Issue:1	Design and synthesis of novel selective estrogen receptor degradation inducers based on the diphenylheptane skeleton.
AID650636	Displacement of [3H]estradiol from rat uterine cytosolic estrogen receptor	2012	Bioorganic & medicinal chemistry, Apr-01, Volume: 20, Issue:7	2-Morpholinoisoflav-3-enes as flexible intermediates in the synthesis of phenoxodiol, isophenoxodiol, equol and analogues: vasorelaxant properties, estrogen receptor binding and Rho/RhoA kinase pathway inhibition.
AID1469737	Downregulation of progesterone receptor mRNA level in NOD SCID gamma mouse xenografted with human MCF7 cells at 5 mg, sc administered once in a week for 48 days post tumor implantation measured 7 hrs post last dose by RT-PCR method	2018	Journal of medicinal chemistry, 04-12, Volume: 61, Issue:7	Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen Receptor Positive Breast Cancer.
AID1728101	Antiproliferative activity against human MDA-MB-231 cells assessed as cell viability after 24 hrs	2021	European journal of medicinal chemistry, Jan-15, Volume: 210	Potent antiproliferative activity of bradykinin B2 receptor selective agonist FR-190997 and analogue structures thereof: A paradox resolved?
AID755454	Antagonist activity at human GTS-tagged FXR after 20 mins by TR-FRET assay	2013	Bioorganic & medicinal chemistry, Jul-15, Volume: 21, Issue:14	Development of time resolved fluorescence resonance energy transfer-based assay for FXR antagonist discovery.
AID1473740	Inhibition of human MRP3 overexpressed in Sf9 insect cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 10 mins by membrane vesicle transport assay	2013	Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1	A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID1690987	Antiproliferative activity against human MCF7 cells assessed as reduction in cell metabolic activity at 20 uM measured after 72 hrs by modified MTT based EZ4U assay relative to control	2020	European journal of medicinal chemistry, Apr-15, Volume: 192	Development of bivalent triarylalkene- and cyclofenil-derived dual estrogen receptor antagonists and downregulators.
AID1474167	Liver toxicity in human assessed as induction of drug-induced liver injury by measuring verified drug-induced liver injury concern status	2016	Drug discovery today, Apr, Volume: 21, Issue:4	DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID70164	In vitro displacement of 0.5 nM [3H]17-beta-estradiol from human Estrogen receptor beta	2003	Journal of medicinal chemistry, Apr-10, Volume: 46, Issue:8	De novo design, synthesis, and evaluation of novel nonsteroidal phenanthrene ligands for the estrogen receptor.
AID1629293	Antiproliferative activity against human T47D cells after 5 days by coulter counter analysis	2016	Journal of medicinal chemistry, 09-08, Volume: 59, Issue:17	Fulvestrant-3 Boronic Acid (ZB716): An Orally Bioavailable Selective Estrogen Receptor Downregulator (SERD).
AID1855797	Antiproliferative activity against human MCF7 cells assessed as inhibition of cell growth	2022	European journal of medicinal chemistry, Nov-05, Volume: 241	An overview on Estrogen receptors signaling and its ligands in breast cancer.
AID1768146	Apparent permeability in MDCK cells across apical to basolateral side at 10 uM incubated for 3 hrs by LC-MS/MS analysis
AID1443551	Antagonist activity at ERalpha in human MCF7 cells assessed as inhibition of estrogen-induced transcription preincubated overnight followed by estrogen addition measured after 24 hrs by dual luciferase reporter gene assay	2017	Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7	Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ERα+ Breast Cancer.
AID1559015	Induction of uterotrophic activity in Sprague-Dawley rat assessed as increase in uterine weight at 2 mg/kg, sc administered for 3 days and measured after 24 hrs of last dosing by hematoxylin eosin staining based imaging analysis	2019	Journal of medicinal chemistry, 12-26, Volume: 62, Issue:24	Design and Synthesis of Basic Selective Estrogen Receptor Degraders for Endocrine Therapy Resistant Breast Cancer.
AID1559000	Plasma concentration in C57BL/6 mouse at 5 mg, sc measured after 0.5 hrs by LC/MS-MS analysis	2019	Journal of medicinal chemistry, 12-26, Volume: 62, Issue:24	Design and Synthesis of Basic Selective Estrogen Receptor Degraders for Endocrine Therapy Resistant Breast Cancer.
AID1811365	Displacement of fluorescent estradiol from full-length ERalpha (unknown origin) measured after 2 hrs by fluorescence polarization assay	2021	European journal of medicinal chemistry, Dec-15, Volume: 226	Development of novel tetrahydroisoquinoline-hydroxamate conjugates as potent dual SERDs/HDAC inhibitors for the treatment of breast cancer.
AID183161	Antagonist effect as ability to suppress uterine stimulatory EE2 effect in immature female rats at 0.1 mg/kg dose	2003	Bioorganic & medicinal chemistry letters, Dec-15, Volume: 13, Issue:24	B-ring unsaturated estrogens: biological evaluation of 17alpha-Dihydroequilein and novel B-Nor-6-thiaequilenins as tissue selective estrogens.
AID1901490	Anticancer activity against human MCF7 cells assessed as reduction in cell viability incubated for 24 hrs in presence of 10% CD-FBS and 17-beta-estradiol by alamar blue assay	2022	Journal of medicinal chemistry, 03-10, Volume: 65, Issue:5	Activators of the Anticipatory Unfolded Protein Response with Enhanced Selectivity for Estrogen Receptor Positive Breast Cancer.
AID1594504	Induction of ERalpha degradation in human MCF7 cells at 1 uM by Western blot analysis	2019	Bioorganic & medicinal chemistry, 05-15, Volume: 27, Issue:10	Structure-activity relationship study of estrogen receptor down-regulators with a diphenylmethane skeleton.
AID232814	Antagonist effect on transcriptional activation by human ER alpha and ER beta on vitellogenin A2 ERE	2003	Journal of medicinal chemistry, Apr-10, Volume: 46, Issue:8	De novo design, synthesis, and evaluation of novel nonsteroidal phenanthrene ligands for the estrogen receptor.
AID1559004	Cytotoxicity against human MCF7:WS8 monolayer cells assessed as reduction in tumor spheroid size at 10 nM incubated for 10 days	2019	Journal of medicinal chemistry, 12-26, Volume: 62, Issue:24	Design and Synthesis of Basic Selective Estrogen Receptor Degraders for Endocrine Therapy Resistant Breast Cancer.
AID1629295	Antiproliferative activity against human tamoxifen-resistant T47D cells over-expressing PKC-alpha after 5 days by coulter counter analysis	2016	Journal of medicinal chemistry, 09-08, Volume: 59, Issue:17	Fulvestrant-3 Boronic Acid (ZB716): An Orally Bioavailable Selective Estrogen Receptor Downregulator (SERD).
AID248712	Inhibition of 10e-9 M E2 stimulated MCF-7 breast cancer cell proliferation	2004	Bioorganic & medicinal chemistry letters, Sep-20, Volume: 14, Issue:18	Synthesis and biological evaluation of stilbene-based pure estrogen antagonists.
AID103267	Inhibition of estrogen-induced proliferation in human MCF-7 breast cancer cells	1997	Journal of medicinal chemistry, May-09, Volume: 40, Issue:10	Discovery and synthesis of [6-hydroxy-3-[4-[2-(1-piperidinyl)ethoxy]phenoxy]-2-(4-hydroxyphenyl)]b enzo[b]thiophene: a novel, highly potent, selective estrogen receptor modulator.
AID436102	Cytotoxicity against human MCF7 cells at 1 uM by MTT assay relative to control in the absence of 17-beta-estradiol	2008	Journal of natural products, Nov, Volume: 71, Issue:11	Ebenfurans IV-VIII from Onobrychis ebenoides: evidence that C-prenylation is the key determinant of the cytotoxicity of 3-formyl-2-arylbenzofurans.
AID1356844	AUC in mouse at 10 mg/kg, po	2018	Journal of medicinal chemistry, 09-13, Volume: 61, Issue:17	Identification of an Orally Bioavailable Chromene-Based Selective Estrogen Receptor Degrader (SERD) That Demonstrates Robust Activity in a Model of Tamoxifen-Resistant Breast Cancer.
AID469727	Antagonist activity at estrogen receptor alpha ligand binding domain expressed in african green monkey COS7 cells co-transfected with Gal4-LBD by luciferase reporter gene assay	2009	Journal of natural products, Nov, Volume: 72, Issue:11	The lecanindoles, nonsteroidal progestins from the terrestrial fungus Verticillium lecanii 6144.
AID1594510	Selective estrogen receptor down-regulator activity at FLAG-tagged ERalpha (unknown origin) expressed in HEK293 cells assessed as induction of ERalpha degradation by luciferase reporter gene assay relative to untreated control	2019	Bioorganic & medicinal chemistry, 05-15, Volume: 27, Issue:10	Structure-activity relationship study of estrogen receptor down-regulators with a diphenylmethane skeleton.
AID1768201	Induction of estrogen receptor degradation in human MCF7 cells at 1 nM measured after 24 hrs by Western blot analysis
AID1228239	Antagonist activity at estrogen receptor in human MCF7 cells assessed as inhibition of 17beta-estradiol-mediated transcriptional activation after 24 hrs by luciferase reporter gene assay	2015	Journal of medicinal chemistry, Jun-25, Volume: 58, Issue:12	Identification of GDC-0810 (ARN-810), an Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts.
AID1906861	Induction of ERalpha degradation in human MCF7 cells at 5 uM incubated 24 hrs by Western blot analysis	2022	Journal of medicinal chemistry, 04-14, Volume: 65, Issue:7	Discovery of Thieno[2,3-
AID271236	AUC in Sprague-Dawley rat at 20 mg/kg, po	2006	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 16, Issue:18	Newly discovered orally active pure antiestrogens.
AID597273	Antiproliferative activity against estrogen receptor-deficient human MCF12A cells incubated with 0.06 nM of estradiol and 0.07 nM of testosterone after 48 hrs by sulforhodamine B assay in presence of fetal bovine serum and NuSerum	2011	Journal of medicinal chemistry, May-26, Volume: 54, Issue:10	Biomimetic syntheses and antiproliferative activities of racemic, natural (-), and unnnatural (+) glyceollin I.
AID1256267	Decrease in estrogen receptor alpha level in human MCF7 cells after 4 hrs by in-cell western assay relative to fulvestrant	2015	Bioorganic & medicinal chemistry letters, Nov-15, Volume: 25, Issue:22	Optimization of an indazole series of selective estrogen receptor degraders: Tumor regression in a tamoxifen-resistant breast cancer xenograft.
AID287687	Activity at ER assessed as suppression of estrogen response element-driven gene transactivation in MVLN cells after 24 hrs by luciferase reporter gene assay	2007	Bioorganic & medicinal chemistry, Mar-15, Volume: 15, Issue:6	Synthesis, structure, and estrogenic activity of 4-amino-3-(2-methylbenzyl)coumarins on human breast carcinoma cells.
AID1443552	Induction of ERalpha degradation in human MCF7 cells assessed as remaining ERalpha protein level at 10 uM after 18 to 24 hrs by Western blot analysis	2017	Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7	Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ERα+ Breast Cancer.
AID242498	Inhibition of human estrogen receptor 2 using tritiated estradiol incubated for 3 hr	2005	Bioorganic & medicinal chemistry letters, Sep-01, Volume: 15, Issue:17	Estrogen receptor ligands. Part 13: Dihydrobenzoxathiin SERAMs with an optimized antagonist side chain.
AID1629304	AUC in C57BL/6 mouse at 8.3 mg/kg, sc by HPLC-MS/MS analysis	2016	Journal of medicinal chemistry, 09-08, Volume: 59, Issue:17	Fulvestrant-3 Boronic Acid (ZB716): An Orally Bioavailable Selective Estrogen Receptor Downregulator (SERD).
AID1283267	Cytotoxicity against human SLOS fibroblasts at 5 uM after 5 days by Cell Titer assay	2016	Journal of medicinal chemistry, Feb-11, Volume: 59, Issue:3	The Effect of Small Molecules on Sterol Homeostasis: Measuring 7-Dehydrocholesterol in Dhcr7-Deficient Neuro2a Cells and Human Fibroblasts.
AID1572958	Antiproliferative activity against human MCF7 cells at 10 to 300 nM after 5 days by crystal violet staining based assay	2019	Journal of medicinal chemistry, 02-14, Volume: 62, Issue:3	Discovery of ERD-308 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Estrogen Receptor (ER).
AID1558991	Inhibition of ERalpha in human MCF7:WS8 cells assessed as increase in degradation of ERalpha incubated for 24 hrs by In-Cell Western assay	2019	Journal of medicinal chemistry, 12-26, Volume: 62, Issue:24	Design and Synthesis of Basic Selective Estrogen Receptor Degraders for Endocrine Therapy Resistant Breast Cancer.
AID1385760	Proteolysis targeting chimera activity in human MCF7 cells assessed as induction of E3 ubiquitin ligase-mediated ERalpha degradation by proteasome after 24 hrs by in-cell Western assay	2018	ACS medicinal chemistry letters, Aug-09, Volume: 9, Issue:8	New Class of Selective Estrogen Receptor Degraders (SERDs): Expanding the Toolbox of PROTAC Degrons.
AID271228	Displacement of [3H]estradiol from recombinant ERalpha relative to estradiol	2006	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 16, Issue:18	Newly discovered orally active pure antiestrogens.
AID468380	Antagonist activity at ERalpha in human MCF7:D5L cells assessed as inhibition of ERE-dependent luciferase expression at 1 uM	2009	Journal of medicinal chemistry, Nov-12, Volume: 52, Issue:21	Novel dehydroepiandrosterone derivatives with antiapoptotic, neuroprotective activity.
AID1768205	Antiproliferative activity against human HCC1500 incubated for 7 to 10 days by celltiter-glo luminescent cell viability assay
AID1768141	Antiproliferative activity against human MCF-7 cells incubated for 72 hrs by Cell-titer Glo assay
AID1690958	Displacement of fluorescent-labelled E2 from recombinant human GST-tagged ERalpha by LanthaScreen TR-FRET assay relative to E2	2020	European journal of medicinal chemistry, Apr-15, Volume: 192	Development of bivalent triarylalkene- and cyclofenil-derived dual estrogen receptor antagonists and downregulators.
AID1594509	Selective estrogen receptor down-regulator activity at FLAG-tagged ERalpha (unknown origin) expressed in HEK293 cells assessed as induction of ERalpha degradation by luciferase reporter gene assay	2019	Bioorganic & medicinal chemistry, 05-15, Volume: 27, Issue:10	Structure-activity relationship study of estrogen receptor down-regulators with a diphenylmethane skeleton.
AID1829664	Displacement of fluorescent-labeled E2 from LBD of ERbeta (unknown origin) by TR-FRET assay
AID497605	Antagonist activity at human ERalpha expressed in human HeLa cells coexpressing ERE-E1b-Luc assessed as inhibition of estradiol-induced transcriptional activation at 1 uM after 48 hrs by luciferase reporter gene assay	2010	Bioorganic & medicinal chemistry, Aug-01, Volume: 18, Issue:15	Genomic action of permanently charged tamoxifen derivatives via estrogen receptor-alpha.
AID176788	In vivo inhibition of estrogen-stimulated uterine weight gain in immature rats on peroral administration	1997	Journal of medicinal chemistry, May-09, Volume: 40, Issue:10	Discovery and synthesis of [6-hydroxy-3-[4-[2-(1-piperidinyl)ethoxy]phenoxy]-2-(4-hydroxyphenyl)]b enzo[b]thiophene: a novel, highly potent, selective estrogen receptor modulator.
AID1829676	Antagonist activity at ERbeta (unknown origin) expressed in human U2OS cells assessed as inhibition of E2-induced transactivation by dual luciferase reporter gene assay
AID269787	AUC in duodenally dosed Sprague-Dawley rat peripheral blood at 10 mg/kg	2006	Bioorganic & medicinal chemistry letters, Aug-01, Volume: 16, Issue:15	Discovery of thiochroman derivatives bearing a carboxy-containing side chain as orally active pure antiestrogens.
AID1446047	Downregulation of ER-alpha levels in ER-positive human MCF-7 cells assessed as ER-alpha levels at 3 uM after 24 hrs relative to vehicle-treated control	2017	Journal of medicinal chemistry, 07-27, Volume: 60, Issue:14	Adamantyl Antiestrogens with Novel Side Chains Reveal a Spectrum of Activities in Suppressing Estrogen Receptor Mediated Activities in Breast Cancer Cells.
AID1658828	Antiproliferative activity against human T47D cells assessed as reduction in cell viability	2020	ACS medicinal chemistry letters, Jun-11, Volume: 11, Issue:6	Discovery of GNE-149 as a Full Antagonist and Efficient Degrader of Estrogen Receptor alpha for ER+ Breast Cancer.
AID1772293	Toxicity in CD1 mouse xenografted with human MCF7 cells assessed as change in body weight at 3 mg/kg, sc administered once daily for 28 days	2021	Journal of medicinal chemistry, 04-22, Volume: 64, Issue:8	Bispecific Estrogen Receptor α Degraders Incorporating Novel Binders Identified Using DNA-Encoded Chemical Library Screening.
AID1256266	Decrease in estrogen receptor alpha level in human MCF7 cells after 4 hrs by in-cell western assay	2015	Bioorganic & medicinal chemistry letters, Nov-15, Volume: 25, Issue:22	Optimization of an indazole series of selective estrogen receptor degraders: Tumor regression in a tamoxifen-resistant breast cancer xenograft.
AID269780	Displacement of [3H]estradiol from human recombinant ERalpha relative to estradiol	2006	Bioorganic & medicinal chemistry letters, Aug-01, Volume: 16, Issue:15	Discovery of thiochroman derivatives bearing a carboxy-containing side chain as orally active pure antiestrogens.
AID736233	Inverse agonist activity at estrogen receptor beta (unknown origin) expressed in human HepG2 cells coexpressing estrogen response element at 10 uM after 24 hrs by luciferase reporter gene assay relative to estradiol	2013	Journal of medicinal chemistry, Apr-25, Volume: 56, Issue:8	Thiophene-core estrogen receptor ligands having superagonist activity.
AID1768142	Kinetic solubility of compound at pH 7.4
AID1906833	Antagonist activity at ERalpha expressed in HEK293/Gal4 cells incubated for 24 hrs in presence of estradiol by luciferase reporter gene assay	2022	Journal of medicinal chemistry, 04-14, Volume: 65, Issue:7	Discovery of Thieno[2,3-
AID1616740	Inhibition of bacterial Beta-lactamase TEM-1 M182T mutant pre-incubated for 5 mins before addition of chromogenic beta-lactamase substrate CENTA by spectrophotometry	2019	Journal of medicinal chemistry, 11-14, Volume: 62, Issue:21	Protein Stability Effects in Aggregate-Based Enzyme Inhibition.
AID755448	Agonist activity at PXR (unknown origin) expressed in human HepG2 cells assessed as induction of CYP3A4 transactivation at 20 uM after 16 hrs by luciferase reporter gene assay	2013	Bioorganic & medicinal chemistry, Jul-15, Volume: 21, Issue:14	Development of time resolved fluorescence resonance energy transfer-based assay for FXR antagonist discovery.
AID269791	Bioavailability in Sprague-Dawley rat	2006	Bioorganic & medicinal chemistry letters, Aug-01, Volume: 16, Issue:15	Discovery of thiochroman derivatives bearing a carboxy-containing side chain as orally active pure antiestrogens.
AID1906839	AUC (0 to t) in Sprague-Dawley rat at 10 mg/kg, po measured up to 24 hrs by LC/MS/MS analysis	2022	Journal of medicinal chemistry, 04-14, Volume: 65, Issue:7	Discovery of Thieno[2,3-
AID1629297	Downregulation of ER-alpha expression in human T47D cells measured after 5 days by Western blot analysis	2016	Journal of medicinal chemistry, 09-08, Volume: 59, Issue:17	Fulvestrant-3 Boronic Acid (ZB716): An Orally Bioavailable Selective Estrogen Receptor Downregulator (SERD).
AID625287	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatomegaly	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1690977	Antiproliferative activity against human MCF7 cells assessed as cell mass at 10 uM measured after 72 hrs by crystal violet staining based assay relative to control	2020	European journal of medicinal chemistry, Apr-15, Volume: 192	Development of bivalent triarylalkene- and cyclofenil-derived dual estrogen receptor antagonists and downregulators.
AID1228300	Antitumor activity against tamoxifen-sensitive human MCF7 cells xenografted in nu/nu mouse supplemented with 17-beta estradiol pellets assessed as tumor stasis at 200 mg/kg, sc administered 3 times per week for 4 weeks measured twice weekly during compoun	2015	Journal of medicinal chemistry, Jun-25, Volume: 58, Issue:12	Identification of GDC-0810 (ARN-810), an Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts.
AID1469739	In vivo inhibition of ER protein level in NOD SCID gamma mouse xenografted with human MCF7 cells at 5 mg, sc administered once in a week for 48 days post tumor implantation measured 7 hrs post last dose by Western blot method relative to control	2018	Journal of medicinal chemistry, 04-12, Volume: 61, Issue:7	Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen Receptor Positive Breast Cancer.
AID427281	Cytotoxicity against human MCF7 cells after 4 days by MTT assay	2009	Bioorganic & medicinal chemistry, Jul-01, Volume: 17, Issue:13	9,11-Secosterols with antiproliferative activity from the gorgonian Eunicella cavolini.
AID1629294	Antiproliferative activity against human tamoxifen-resistant MCF7 cells after 5 days by coulter counter analysis	2016	Journal of medicinal chemistry, 09-08, Volume: 59, Issue:17	Fulvestrant-3 Boronic Acid (ZB716): An Orally Bioavailable Selective Estrogen Receptor Downregulator (SERD).
AID1811383	Stability in human liver microsomes assessed as half life	2021	European journal of medicinal chemistry, Dec-15, Volume: 226	Development of novel tetrahydroisoquinoline-hydroxamate conjugates as potent dual SERDs/HDAC inhibitors for the treatment of breast cancer.
AID625284	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic failure	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1443550	Displacement of [3H]-estradiol from recombinant human N-terminal His-tagged ERalpha LBD harboring C381S/C417S/C530S mutant expressed in Rosetta 2 DE3 competent cells after 1 hr by SPA binding assay	2017	Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7	Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ERα+ Breast Cancer.
AID269786	AUC in duodenally dosed Sprague-Dawley rat portal vein at 10 mg/kg	2006	Bioorganic & medicinal chemistry letters, Aug-01, Volume: 16, Issue:15	Discovery of thiochroman derivatives bearing a carboxy-containing side chain as orally active pure antiestrogens.
AID1768145	Clearance in Sprague-Dawley rat at 1 mg/kg, iv or po measured after 0.033 to 24 hrs by LC/MS/MS analysis
AID1768204	Antiproliferative activity against human CAMA-1 incubated for 7 to 10 days by celltiter-glo luminescent cell viability assay
AID1629289	Antiestrogenic activity at estrogen receptor in human T47D-KBluc cells assessed as inhibition of estradiol activity by luciferase reporter gene assay relative to estradiol control	2016	Journal of medicinal chemistry, 09-08, Volume: 59, Issue:17	Fulvestrant-3 Boronic Acid (ZB716): An Orally Bioavailable Selective Estrogen Receptor Downregulator (SERD).
AID1768218	Antitumor activity against human MCF7 cells xenografted in nude mouse assessed as reduction in tumor growth at 50 mg/kg, sc administered once daily at day 1,3 and 8 followed by 25 mg/kg dosed twice weekly for 2 to 4 weeks cotreated with palbociclib and me
AID1629303	Cmax in C57BL/6 mouse at 8.3 mg/kg, sc by HPLC-MS/MS analysis	2016	Journal of medicinal chemistry, 09-08, Volume: 59, Issue:17	Fulvestrant-3 Boronic Acid (ZB716): An Orally Bioavailable Selective Estrogen Receptor Downregulator (SERD).
AID1572955	Inhibition of cell growth in human MCF7 cells after 4 days by wst-8-based colorimetric analysis relative to control	2019	Journal of medicinal chemistry, 02-14, Volume: 62, Issue:3	Discovery of ERD-308 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Estrogen Receptor (ER).
AID1658829	Induction of ERalpha degradation in human T47D cells	2020	ACS medicinal chemistry letters, Jun-11, Volume: 11, Issue:6	Discovery of GNE-149 as a Full Antagonist and Efficient Degrader of Estrogen Receptor alpha for ER+ Breast Cancer.
AID1536996	Induction of VP16-labeled ERalpha (unknown origin) conformational changes ezpressed in HEK293T cells after 24 hrs by luciferase reporter gene assay	2019	ACS medicinal chemistry letters, Jan-10, Volume: 10, Issue:1	Maximizing ER-α Degradation Maximizes Activity in a Tamoxifen-Resistant Breast Cancer Model: Identification of GDC-0927.
AID1228205	Induction of estrogen receptor-alpha degradation in human MCF7 cells after 4 hrs by in-cell western assay	2015	Journal of medicinal chemistry, Jun-25, Volume: 58, Issue:12	Identification of GDC-0810 (ARN-810), an Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts.
AID549848	Displacement of fluorescent estrogen ES2 from human recombinant ERbeta by fluorescence polarization assay relative to estradiol	2011	Bioorganic & medicinal chemistry, Jan-01, Volume: 19, Issue:1	New hydroxystilbenoid derivatives endowed with neuroprotective activity and devoid of interference with estrogen and aryl hydrocarbon receptor-mediated transcription.
AID473607	Down regulation of ERalpha expression in human MCF7 cell insoluble fraction at 1 uM after 16 hrs by Western blotting	2010	Journal of medicinal chemistry, Apr-22, Volume: 53, Issue:8	Characterization of the pharmacophore properties of novel selective estrogen receptor downregulators (SERDs).
AID1681458	Agonist activity at ERalpha in human MCF7 cells assessed as increase in PGR mRNA expression level at 100 nM measured after 24 hrs	2020	Journal of medicinal chemistry, 12-10, Volume: 63, Issue:23	Discovery of AZD9833, a Potent and Orally Bioavailable Selective Estrogen Receptor Degrader and Antagonist.
AID1829665	Displacement of fluorescent-labeled E2 from LBD of ERalpha (unknown origin) assessed as relative binding affinity by TR-FRET assay relative to control
AID271229	Antagonist effect on estrogen activity assessed as inhibition of estrogen-stimulated uterine weight gain in ovariectomized mouse at 1 mg/kg, po	2006	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 16, Issue:18	Newly discovered orally active pure antiestrogens.
AID269785	Agonist activity assessed as increase in uterine weight in ovariectomized mouse at 10 mg/kg, sc	2006	Bioorganic & medicinal chemistry letters, Aug-01, Volume: 16, Issue:15	Discovery of thiochroman derivatives bearing a carboxy-containing side chain as orally active pure antiestrogens.
AID1681456	Agonist activity at ERalpha in human MCF7 cells assessed as increase in GREB1 mRNA expression level at 100 nM measured after 24 hrs	2020	Journal of medicinal chemistry, 12-10, Volume: 63, Issue:23	Discovery of AZD9833, a Potent and Orally Bioavailable Selective Estrogen Receptor Degrader and Antagonist.
AID1616742	Inhibition of bacterial wild type Beta-lactamase TEM-1 pre-incubated for 5 mins before addition of chromogenic beta-lactamase substrate CENTA by spectrophotometry	2019	Journal of medicinal chemistry, 11-14, Volume: 62, Issue:21	Protein Stability Effects in Aggregate-Based Enzyme Inhibition.
AID1572967	Induction of ERalpha degradation in human MCF7 cells assessed as effect on ER protein/GADPH ratio at 100 nM after 4 hrs by Western blot analysis relative to control	2019	Journal of medicinal chemistry, 02-14, Volume: 62, Issue:3	Discovery of ERD-308 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Estrogen Receptor (ER).
AID1356848	Induction of ERalpha degradation in human MCF7 cells in phenol red free RPMI medium containing 5% charcoal dextran-treated FBS incubated for 4 hrs by SP1 and anti-ER rabbit monocolnal antibody based in-cell Western assay relative to fulvestrant	2018	Journal of medicinal chemistry, 09-13, Volume: 61, Issue:17	Identification of an Orally Bioavailable Chromene-Based Selective Estrogen Receptor Degrader (SERD) That Demonstrates Robust Activity in a Model of Tamoxifen-Resistant Breast Cancer.
AID1690956	Displacement of fluorescent-labelled E2 from recombinant human GST-tagged ERalpha by LanthaScreen TR-FRET assay	2020	European journal of medicinal chemistry, Apr-15, Volume: 192	Development of bivalent triarylalkene- and cyclofenil-derived dual estrogen receptor antagonists and downregulators.
AID499834	Antiestrogenic activity in human MCF7 cells xenografted in ovariectomized Nu/Nu mouse assessed as decrease of estradiol-induced tumor volume at 50 mg/kg, daily once for 21 days	2010	Journal of medicinal chemistry, Aug-26, Volume: 53, Issue:16	Effects of 7-O substitutions on estrogenic and anti-estrogenic activities of daidzein analogues in MCF-7 breast cancer cells.
AID419507	Volume of distribution at steady state in human dosed 1 hr iv infusion	2009	Journal of medicinal chemistry, Jul-23, Volume: 52, Issue:14	In silico prediction of volume of distribution in human using linear and nonlinear models on a 669 compound data set.
AID1251780	Binding affinity to ERalpha receptor (unknown origin)	2015	Journal of medicinal chemistry, Oct-22, Volume: 58, Issue:20	Optimization of a Novel Binding Motif to (E)-3-(3,5-Difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic Acid (AZD9496), a Potent and Orally Bioavailable Selective Estrogen Receptor Downregu
AID625285	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic necrosis	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1473738	Inhibition of human BSEP overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-taurocholate in presence of ATP measured after 15 to 20 mins by membrane vesicle transport assay	2013	Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1	A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID1385761	Proteolysis targeting chimera activity in human MCF7 cells assessed as induction of E3 ubiquitin ligase-mediated ERalpha level after 24 hrs by in-cell Western assay relative to control	2018	ACS medicinal chemistry letters, Aug-09, Volume: 9, Issue:8	New Class of Selective Estrogen Receptor Degraders (SERDs): Expanding the Toolbox of PROTAC Degrons.
AID1469718	Induction of selective estrogen receptor alpha degradation in human MCF7 cells assessed as ERalpha remaining at 10 uM after 18 to 24 hrs by in-cell Western analysis relative to control	2018	Journal of medicinal chemistry, 04-12, Volume: 61, Issue:7	Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen Receptor Positive Breast Cancer.
AID1559011	Induction of degradation of ERalpha in human MCF7:WS8 cells at 100 nM in presence of MG-132 incubated for 24 hrs by Western blot analysis	2019	Journal of medicinal chemistry, 12-26, Volume: 62, Issue:24	Design and Synthesis of Basic Selective Estrogen Receptor Degraders for Endocrine Therapy Resistant Breast Cancer.
AID68907	Apparent inhibition constant for estrogen receptor in Human uterine cytosol in 2.5%DMF	1997	Journal of medicinal chemistry, Jul-04, Volume: 40, Issue:14	(S)-(+)-4-[7-(2,2-dimethyl-1-oxopropoxy)-4-methyl-2-[4-[2-(1-piperidinyl)-ethoxy]phenyl]-2H-1-benzopyran-3-yl]-phenyl 2,2-dimethylpropanoate (EM-800): a highly potent, specific, and orally active nonsteroidal antiestrogen.
AID597276	Antiproliferative activity against androgen receptor-deficient human DU145 cells incubated with 0.6 nM of estradiol and 0.7 nM of testosterone after 48 hrs by sulforhodamine B assay	2011	Journal of medicinal chemistry, May-26, Volume: 54, Issue:10	Biomimetic syntheses and antiproliferative activities of racemic, natural (-), and unnnatural (+) glyceollin I.
AID1906837	Cmax in Sprague-Dawley rat at 10 mg/kg, po measured up to 24 hrs by LC/MS/MS analysis	2022	Journal of medicinal chemistry, 04-14, Volume: 65, Issue:7	Discovery of Thieno[2,3-
AID1283269	Inhibition of DR24 in Dhcr7-deficient mouse Neuro2a cells assessed as decrease in 7-DHC levels at 1 uM by LC-MS/GC-MS analysis	2016	Journal of medicinal chemistry, Feb-11, Volume: 59, Issue:3	The Effect of Small Molecules on Sterol Homeostasis: Measuring 7-Dehydrocholesterol in Dhcr7-Deficient Neuro2a Cells and Human Fibroblasts.
AID269792	Antagonist activity assessed as inhibition of estrogen-stimulated uterine weight gain in ovariectomized mouse at 3 mg/kg, po	2006	Bioorganic & medicinal chemistry letters, Aug-01, Volume: 16, Issue:15	Discovery of thiochroman derivatives bearing a carboxy-containing side chain as orally active pure antiestrogens.
AID473420	Down regulation of ERalpha expression in human MCF7 cell cytoplasmic fraction at 1 uM after 16 hrs by Western blotting	2010	Journal of medicinal chemistry, Apr-22, Volume: 53, Issue:8	Characterization of the pharmacophore properties of novel selective estrogen receptor downregulators (SERDs).
AID1768136	Unbound clearance in Sprague-Dawley rat at 1 mg/kg, iv or po measured after 0.033 to 24 hrs by LC/MS/MS analysis
AID1811368	Induction of ERalpha degradation in human MCF7 cells at 0.1 uM measured after 24 hrs by Western blot analysis	2021	European journal of medicinal chemistry, Dec-15, Volume: 226	Development of novel tetrahydroisoquinoline-hydroxamate conjugates as potent dual SERDs/HDAC inhibitors for the treatment of breast cancer.
AID1473739	Inhibition of human MRP2 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	2013	Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1	A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID549847	Selectivity ratio, ratio of RBA for human recombinant ERbeta to RBA for human recombinant ERalpha	2011	Bioorganic & medicinal chemistry, Jan-01, Volume: 19, Issue:1	New hydroxystilbenoid derivatives endowed with neuroprotective activity and devoid of interference with estrogen and aryl hydrocarbon receptor-mediated transcription.
AID1829693	Antiproliferative activity on human MCF7 cells at 5 to 20 uM assessed as ratio of T/C measured up to 144 hrs relative to control
AID1690969	Antagonist activity at ERalpha (unknown origin) expressed in human U2OS cells assessed as inhibition of E2-induced transactivation measured after 21 hrs by dual luciferase reporter gene assay	2020	European journal of medicinal chemistry, Apr-15, Volume: 192	Development of bivalent triarylalkene- and cyclofenil-derived dual estrogen receptor antagonists and downregulators.
AID297564	Binding affinity to human ERalpha	2007	Journal of medicinal chemistry, Sep-06, Volume: 50, Issue:18	Design, synthesis, and estrogenic activity of a novel estrogen receptor modulator--a hybrid structure of 17beta-estradiol and vitamin E in hippocampal neurons.
AID1251815	Degradation activity of ERalpha receptor in human MCF7 cells at 0.01 to 300 nM after 48 hrs by Western blot analysis	2015	Journal of medicinal chemistry, Oct-22, Volume: 58, Issue:20	Optimization of a Novel Binding Motif to (E)-3-(3,5-Difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic Acid (AZD9496), a Potent and Orally Bioavailable Selective Estrogen Receptor Downregu
AID1559017	Antitumor activity against human MCF7:TAM1 cells xenografted in athymic nude mouse assessed as tumor regression at 5 mg, sc measured after 4 weeks	2019	Journal of medicinal chemistry, 12-26, Volume: 62, Issue:24	Design and Synthesis of Basic Selective Estrogen Receptor Degraders for Endocrine Therapy Resistant Breast Cancer.
AID304031	Inhibition of 30 nM estradiol induced stimulation of DNA synthesis in human MLS cells assessed as ratio of treated to untreated control at 1.1 uM after 48 hrs by [3H]thymidine incorporation assay	2007	Journal of medicinal chemistry, Dec-13, Volume: 50, Issue:25	Synthesis and evaluation of the antiproliferative activities of derivatives of carboxyalkyl isoflavones linked to N-t-Boc-hexylenediamine.
AID368183	Antiproliferative activity against estradiol-stimulated human MCF7 cells after 3 days at 10 nM by crystal violet staining	2009	Journal of medicinal chemistry, Feb-12, Volume: 52, Issue:3	Effect of fluorination on the pharmacological profile of 11beta isomers of fulvestrant in breast carcinoma cells.
AID1572318	Antagonist activity at ERalpha in human MCF7 cells assessed as inhibition of estradiol-driven cell growth measured after 7 days by SYTOX green-based assay	2019	Journal of medicinal chemistry, 02-14, Volume: 62, Issue:3	Tricyclic Indazoles-A Novel Class of Selective Estrogen Receptor Degrader Antagonists.
AID597272	Antiproliferative activity against estrogen receptor-deficient human MCF12A cells incubated with 0.003 nM of estradiol and 0.01 nM of testosterone after 48 hrs by sulforhodamine B assay in presence of 5% fetal bovine serum	2011	Journal of medicinal chemistry, May-26, Volume: 54, Issue:10	Biomimetic syntheses and antiproliferative activities of racemic, natural (-), and unnnatural (+) glyceollin I.
AID1559002	Drug concentration in C57BL/6 mouse brain at 5 mg, sc measured after 0.5 hrs by LC/MS-MS analysis	2019	Journal of medicinal chemistry, 12-26, Volume: 62, Issue:24	Design and Synthesis of Basic Selective Estrogen Receptor Degraders for Endocrine Therapy Resistant Breast Cancer.
AID1559006	Cytotoxicity against human MCF7:TAM1 monolayer cells assessed as reduction in tumor cell viability at 10 nM incubated for 10 days by celltiter-glo 3D cell viability assay	2019	Journal of medicinal chemistry, 12-26, Volume: 62, Issue:24	Design and Synthesis of Basic Selective Estrogen Receptor Degraders for Endocrine Therapy Resistant Breast Cancer.
AID176790	In vivo inhibition of estrogen-stimulated uterine weight gain in immature rats on subcutaneous administration	1997	Journal of medicinal chemistry, May-09, Volume: 40, Issue:10	Discovery and synthesis of [6-hydroxy-3-[4-[2-(1-piperidinyl)ethoxy]phenoxy]-2-(4-hydroxyphenyl)]b enzo[b]thiophene: a novel, highly potent, selective estrogen receptor modulator.
AID625291	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver function tests abnormal	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1572961	Induction of ERalpha degradation in human MCF7 cells assessed as effect on ER protein/GADPH ratio at 1 nM after 4 hrs by Western blot analysis relative to control	2019	Journal of medicinal chemistry, 02-14, Volume: 62, Issue:3	Discovery of ERD-308 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Estrogen Receptor (ER).
AID1768138	Antagonist activity at estrogen receptor in human T47D cells incubated for 18 hrs by ultra high sensitivity luminescence reporter gene assay
AID1742983	Inhibition of SIRT5 (unknown origin)	2020	European journal of medicinal chemistry, Nov-15, Volume: 206	Identification of the subtype-selective Sirt5 inhibitor balsalazide through systematic SAR analysis and rationalization via theoretical investigations.
AID1690990	Cytotoxicity against African green monkey COS7 cells assessed as reduction in cell metabolic activity up to 20 uM measured after 72 hrs by modified MTT based EZ4U assay	2020	European journal of medicinal chemistry, Apr-15, Volume: 192	Development of bivalent triarylalkene- and cyclofenil-derived dual estrogen receptor antagonists and downregulators.
AID1681443	In vivo antagonist activity at ERalpha in human MCF7 cells xenografted CB17 SCID mouse assessed as decrease in PR expression level at 5 mg, po administered via gavage three times a week for 21 days measured 24 hrs post last dose by Western blot analysis	2020	Journal of medicinal chemistry, 12-10, Volume: 63, Issue:23	Discovery of AZD9833, a Potent and Orally Bioavailable Selective Estrogen Receptor Degrader and Antagonist.
AID1768213	Antitumor activity against patient-derived human HCI-013 cells harboring ESR1 Y537S mutant xenografted in NOD SCID mouse assessed as reduction in tumor growth at 50 mg/kg, sc administered once daily at day 1,3 and 8 followed by 25 mg/kg dosed twice weekly
AID304030	Inhibition of DNA synthesis in human 320DM cells assessed as ratio of treated to untreated control at 1.1 uM after 48 hrs by [3H]thymidine incorporation assay	2007	Journal of medicinal chemistry, Dec-13, Volume: 50, Issue:25	Synthesis and evaluation of the antiproliferative activities of derivatives of carboxyalkyl isoflavones linked to N-t-Boc-hexylenediamine.
AID427279	Cytotoxicity against human LNCAP cells after 4 days by MTT assay	2009	Bioorganic & medicinal chemistry, Jul-01, Volume: 17, Issue:13	9,11-Secosterols with antiproliferative activity from the gorgonian Eunicella cavolini.
AID1572968	Induction of ERalpha degradation in human MCF7 cells assessed as effect on ER protein/GADPH ratio at 1000 nM after 4 hrs by Western blot analysis relative to control	2019	Journal of medicinal chemistry, 02-14, Volume: 62, Issue:3	Discovery of ERD-308 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Estrogen Receptor (ER).
AID1906834	Inhibition of human ERG potassium channel expressed in CHO cells by patch-clamp assay	2022	Journal of medicinal chemistry, 04-14, Volume: 65, Issue:7	Discovery of Thieno[2,3-
AID1768202	Antiproliferative activity against human MCF7 incubated for 7 to 10 days by celltiter-glo luminescent cell viability assay
AID70321	Displacement of [3H]17-beta-estradiol from human Estrogen receptor alpha	2000	Bioorganic & medicinal chemistry letters, Jan-17, Volume: 10, Issue:2	Synthesis and estrogenic activities of novel 7-thiosubstituted estratriene derivatives.
AID1385758	Antiproliferative activity against human MCF7 cells after 6 days by WST-1 assay	2018	ACS medicinal chemistry letters, Aug-09, Volume: 9, Issue:8	New Class of Selective Estrogen Receptor Degraders (SERDs): Expanding the Toolbox of PROTAC Degrons.
AID1811382	Lipophilicity, logD of compound in n-octanol and phosphate buffer at pH 7.4 after 1.5 hrs by HPLC analysis	2021	European journal of medicinal chemistry, Dec-15, Volume: 226	Development of novel tetrahydroisoquinoline-hydroxamate conjugates as potent dual SERDs/HDAC inhibitors for the treatment of breast cancer.
AID549849	Displacement of fluorescent estrogen ES2 from human recombinant ERalpha by fluorescence polarization assay relative to estradiol	2011	Bioorganic & medicinal chemistry, Jan-01, Volume: 19, Issue:1	New hydroxystilbenoid derivatives endowed with neuroprotective activity and devoid of interference with estrogen and aryl hydrocarbon receptor-mediated transcription.
AID625288	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for jaundice	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1446059	Downregulation of ERalpha in human MCF-7 cells assessed as reduction of estradiol-induced PgR mRNA levels at 3 x 10'-9 M, 3 x 10'-8 M, 3 x 10'-7 M, 3 x 10'-6 M after 24 hrs by RT-PCR method	2017	Journal of medicinal chemistry, 07-27, Volume: 60, Issue:14	Adamantyl Antiestrogens with Novel Side Chains Reveal a Spectrum of Activities in Suppressing Estrogen Receptor Mediated Activities in Breast Cancer Cells.
AID68906	Inhibition of estradiol binding to estrogen receptor in Human Breast cancer cytosol (3.3% ethanol)	1997	Journal of medicinal chemistry, Jul-04, Volume: 40, Issue:14	(S)-(+)-4-[7-(2,2-dimethyl-1-oxopropoxy)-4-methyl-2-[4-[2-(1-piperidinyl)-ethoxy]phenyl]-2H-1-benzopyran-3-yl]-phenyl 2,2-dimethylpropanoate (EM-800): a highly potent, specific, and orally active nonsteroidal antiestrogen.
AID269789	Total clearance in Sprague-Dawley rat at 10 mg/kg, iv	2006	Bioorganic & medicinal chemistry letters, Aug-01, Volume: 16, Issue:15	Discovery of thiochroman derivatives bearing a carboxy-containing side chain as orally active pure antiestrogens.
AID485979	Inhibition of CETP in rabbit serum at 10 uM after 1 hr by fluorescent cholesteryl esters transfer assay	2010	European journal of medicinal chemistry, Apr, Volume: 45, Issue:4	Discovery of new cholesteryl ester transfer protein inhibitors via ligand-based pharmacophore modeling and QSAR analysis followed by synthetic exploration.
AID1768144	Intrinsic clearance in rat hepatocytes measured up to 60 mins by LC/MS/MS analysis
AID755455	Antagonist activity at human GTS-tagged FXR at 15 uM after 20 mins by TR-FRET assay	2013	Bioorganic & medicinal chemistry, Jul-15, Volume: 21, Issue:14	Development of time resolved fluorescence resonance energy transfer-based assay for FXR antagonist discovery.
AID368326	Displacement of [3H]estradiol from human recombinant estrogen receptor alpha by radiometric assay relative to estradiol	2009	Journal of medicinal chemistry, Feb-12, Volume: 52, Issue:3	Effect of fluorination on the pharmacological profile of 11beta isomers of fulvestrant in breast carcinoma cells.
AID1829677	Induction of ERalpha degradation in human MCF7 cells assessed as ERalpha remaining level at 1 uM incubated for 72 hrs by Western immuno assay relative to control
AID1558988	Antiproliferative activity against human MCF7:5C cells assessed as reduction in cell viability incubated for 7 days by Hoechst 33258 dye based assay relative to control	2019	Journal of medicinal chemistry, 12-26, Volume: 62, Issue:24	Design and Synthesis of Basic Selective Estrogen Receptor Degraders for Endocrine Therapy Resistant Breast Cancer.
AID245770	Inhibition of ER-MDA-MB 231 breast cancer cell proliferation over 96 hr at 10 uM	2004	Bioorganic & medicinal chemistry letters, Sep-20, Volume: 14, Issue:18	Synthesis and biological evaluation of stilbene-based pure estrogen antagonists.
AID1906835	Antagonist activity at ERbeta expressed in HEK293/Gal4 cells incubated for 24 hrs in presence of di-arylpropionitrile by luciferase reporter gene assay	2022	Journal of medicinal chemistry, 04-14, Volume: 65, Issue:7	Discovery of Thieno[2,3-
AID436099	Cytotoxicity against human MCF7 cells at 1 uM by MTT assay relative to control in presence of 17-beta-estradiol	2008	Journal of natural products, Nov, Volume: 71, Issue:11	Ebenfurans IV-VIII from Onobrychis ebenoides: evidence that C-prenylation is the key determinant of the cytotoxicity of 3-formyl-2-arylbenzofurans.
AID1469728	Antiproliferative activity against human MCF7 cells after 6 days in presence of estradiol by CellTiter-Glo assay	2018	Journal of medicinal chemistry, 04-12, Volume: 61, Issue:7	Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen Receptor Positive Breast Cancer.
AID1690980	Cytotoxicity against African green monkey COS7 cells assessed as reduction in cell mass measured after 72 hrs by crystal violet staining based assay	2020	European journal of medicinal chemistry, Apr-15, Volume: 192	Development of bivalent triarylalkene- and cyclofenil-derived dual estrogen receptor antagonists and downregulators.
AID1768200	Induction of estrogen receptor degradation in human MCF7 cells assessed as protein turn over by measuring half life at 1 nM measured after 0.5 to 24 hrs by Western blot analysis
AID597268	Antiproliferative activity against estrogen receptor-deficient human NCI-ADR-RES cells incubated with 100 nM of estradiol and 0.07 nM of testosterone after 48 hrs by sulforhodamine B assay in presence of fetal bovine serum and NuSerum	2011	Journal of medicinal chemistry, May-26, Volume: 54, Issue:10	Biomimetic syntheses and antiproliferative activities of racemic, natural (-), and unnnatural (+) glyceollin I.
AID1594511	Agonist activity at FLAG-tagged ERalpha (unknown origin) expressed in HEK293 cells assessed as induction of ER-alpha-mediated transcriptional activity at 10 uM by luciferase reporter gene assay	2019	Bioorganic & medicinal chemistry, 05-15, Volume: 27, Issue:10	Structure-activity relationship study of estrogen receptor down-regulators with a diphenylmethane skeleton.
AID271235	Total clearance in Sprague-Dawley rat at 10 mg/kg, iv	2006	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 16, Issue:18	Newly discovered orally active pure antiestrogens.
AID468985	Inhibition of human 17beta-HSD7 expressed in HEK293 cells assessed as inhibition of reduction of [14C]estrone into [14C]estradiol at 3 uM after 7 hrs	2009	Journal of medicinal chemistry, Dec-10, Volume: 52, Issue:23	Potent and selective steroidal inhibitors of 17beta-hydroxysteroid dehydrogenase type 7, an enzyme that catalyzes the reduction of the key hormones estrone and dihydrotestosterone.
AID287690	Inhibition of increase in proliferation of estrogen receptor expressing MCF7 cells at 10 uM after 3 days	2007	Bioorganic & medicinal chemistry, Mar-15, Volume: 15, Issue:6	Synthesis, structure, and estrogenic activity of 4-amino-3-(2-methylbenzyl)coumarins on human breast carcinoma cells.
AID1629298	Downregulation of ER-alpha expression in human tamoxifen-resistant T47D cells over-expressing PKC-alpha measured after 5 days by Western blot analysis	2016	Journal of medicinal chemistry, 09-08, Volume: 59, Issue:17	Fulvestrant-3 Boronic Acid (ZB716): An Orally Bioavailable Selective Estrogen Receptor Downregulator (SERD).
AID1551108	Induction of ERalpha protein degradation in human MCF7 cells assessed as ERalpha protein level incubated for 20 hrs by Western blot analysis relative to control	2019	European journal of medicinal chemistry, Jun-15, Volume: 172	Exploring the PROTAC degron candidates: OBHSA with different side chains as novel selective estrogen receptor degraders (SERDs).
AID1256269	Cytotoxicity against human MCF7 cells assessed as decrease in cell viability after 5 days by celltiterGlo assay	2015	Bioorganic & medicinal chemistry letters, Nov-15, Volume: 25, Issue:22	Optimization of an indazole series of selective estrogen receptor degraders: Tumor regression in a tamoxifen-resistant breast cancer xenograft.
AID1251782	Agonist activity at progesterone receptor in human MCF7 cells	2015	Journal of medicinal chemistry, Oct-22, Volume: 58, Issue:20	Optimization of a Novel Binding Motif to (E)-3-(3,5-Difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic Acid (AZD9496), a Potent and Orally Bioavailable Selective Estrogen Receptor Downregu
AID269783	Antagonist activity assessed as inhibition of estrogen-stimulated uterine weight gain in ovariectomized mouse at 50 mg/kg, po	2006	Bioorganic & medicinal chemistry letters, Aug-01, Volume: 16, Issue:15	Discovery of thiochroman derivatives bearing a carboxy-containing side chain as orally active pure antiestrogens.
AID368182	Binding affinity to estrogen receptor alpha in human MCF7 cells assessed as inhibition of [3H]E2 accumulation after 45 mins by whole cell competition binding assay	2009	Journal of medicinal chemistry, Feb-12, Volume: 52, Issue:3	Effect of fluorination on the pharmacological profile of 11beta isomers of fulvestrant in breast carcinoma cells.
AID625290	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver fatty	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1654148	Anti-estrogenic activity in human MCF7 cells assessed as reduction in 17beta-estradiol-induced cell viability at 100 nM after 24 hrs by MTT assay	2020	Journal of natural products, 02-28, Volume: 83, Issue:2	Absolute Configuration and Corrected NMR Assignment of 17-Hydroxycyclooctatin, a Fused 5-8-5 Tricyclic Diterpene.
AID368181	Antiestrogenic activity at human recombinant estrogen receptor alpha assessed as inhibition of recruitment of LxxLL-containing coactivators after 30 mins by ELISA in absence of estradiol	2009	Journal of medicinal chemistry, Feb-12, Volume: 52, Issue:3	Effect of fluorination on the pharmacological profile of 11beta isomers of fulvestrant in breast carcinoma cells.
AID1811379	Antiproliferative activity against human MDA-MB-231 cells assessed as reduction in cell growth measured after 2 days by CCK8 assay	2021	European journal of medicinal chemistry, Dec-15, Volume: 226	Development of novel tetrahydroisoquinoline-hydroxamate conjugates as potent dual SERDs/HDAC inhibitors for the treatment of breast cancer.
AID183162	Antagonist effect as ability to suppress uterine stimulatory EE2 effect in immature female rats at 1.0 mg/kg dose	2003	Bioorganic & medicinal chemistry letters, Dec-15, Volume: 13, Issue:24	B-ring unsaturated estrogens: biological evaluation of 17alpha-Dihydroequilein and novel B-Nor-6-thiaequilenins as tissue selective estrogens.
AID1535225	Induction of ERalpha degradation in human MCF7 cells in phenol red free RPMI medium containing 5% charcoal-stripped FBS incubated for 4 hrs by IRDye 800CW/DRAQ5 dye based in-cell Western assay relative to fulvestrant	2019	Bioorganic & medicinal chemistry letters, 02-01, Volume: 29, Issue:3	Selective estrogen receptor degraders with novel structural motifs induce regression in a tamoxifen-resistant breast cancer xenograft.
AID368184	Antiproliferative activity against human MCF7 cells after 3 days at 10 nM by crystal violet staining	2009	Journal of medicinal chemistry, Feb-12, Volume: 52, Issue:3	Effect of fluorination on the pharmacological profile of 11beta isomers of fulvestrant in breast carcinoma cells.
AID427278	Growth inhibition of human LNCAP cells at 1 uM after 4 days by MTT assay	2009	Bioorganic & medicinal chemistry, Jul-01, Volume: 17, Issue:13	9,11-Secosterols with antiproliferative activity from the gorgonian Eunicella cavolini.
AID269784	Antagonist activity assessed as inhibition of estrogen-stimulated uterine weight gain in ovariectomized mouse at 30 mg/kg, po	2006	Bioorganic & medicinal chemistry letters, Aug-01, Volume: 16, Issue:15	Discovery of thiochroman derivatives bearing a carboxy-containing side chain as orally active pure antiestrogens.
AID1681452	Induction of ERalpha degradation in human CAMA-1 cells incubated for 48 hrs by Western blot analysis	2020	Journal of medicinal chemistry, 12-10, Volume: 63, Issue:23	Discovery of AZD9833, a Potent and Orally Bioavailable Selective Estrogen Receptor Degrader and Antagonist.
AID1690971	Selective estrogen receptor alpha degrader activity in human MCF7 cells assessed as residual ERalpha level at 1 uM measured after 24 hrs by Western blot analysis (Rvb = 100%)	2020	European journal of medicinal chemistry, Apr-15, Volume: 192	Development of bivalent triarylalkene- and cyclofenil-derived dual estrogen receptor antagonists and downregulators.
AID1572954	Inhibition of cell growth in human MCF7 cells after 4 days by wst-8-based colorimetric analysis	2019	Journal of medicinal chemistry, 02-14, Volume: 62, Issue:3	Discovery of ERD-308 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Estrogen Receptor (ER).
AID1565146	Induction of ERalpha degradation in human MCF7 cells assessed as decrease in ERalpha protein expression at 1 uM incubated for 24 hrs by Western blot analysis relative to control	2019	European journal of medicinal chemistry, Nov-15, Volume: 182	Novel class of 7-Oxabicyclo[2.2.1]heptene sulfonamides with long alkyl chains displaying improved estrogen receptor α degradation activity.
AID1616744	Inhibition of bacterial Beta-lactamase TEM-1 G238S mutant pre-incubated for 5 mins before addition of chromogenic beta-lactamase substrate CENTA by spectrophotometry	2019	Journal of medicinal chemistry, 11-14, Volume: 62, Issue:21	Protein Stability Effects in Aggregate-Based Enzyme Inhibition.
AID70189	Agonist effect on transcriptional activation in MCF-7 cells expressing estrogen receptor alpha; Not active means no effect at < 1000 nM	2000	Bioorganic & medicinal chemistry letters, Jan-17, Volume: 10, Issue:2	Synthesis and estrogenic activities of novel 7-thiosubstituted estratriene derivatives.
AID1829678	Induction of ERalpha degradation in human MCF7 cells assessed as efficacy at 1 uM incubated for 72 hrs by Western immuno assay relative to control
AID597270	Antiproliferative activity against human MCF7 cells expressing estrogen receptor incubated with 0.003 nM of estradiol and 0.01 nM of testosterone after 48 hrs by sulforhodamine B assay in presence of 5% fetal bovine serum	2011	Journal of medicinal chemistry, May-26, Volume: 54, Issue:10	Biomimetic syntheses and antiproliferative activities of racemic, natural (-), and unnnatural (+) glyceollin I.
AID1356847	Induction of ERalpha degradation in human MCF7 cells in phenol red free RPMI medium containing 5% charcoal dextran-treated FBS incubated for 4 hrs by SP1 and anti-ER rabbit monocolnal antibody based in-cell Western assay	2018	Journal of medicinal chemistry, 09-13, Volume: 61, Issue:17	Identification of an Orally Bioavailable Chromene-Based Selective Estrogen Receptor Degrader (SERD) That Demonstrates Robust Activity in a Model of Tamoxifen-Resistant Breast Cancer.
AID1558992	Inhibition of ERalpha in human MCF7:WS8 cells assessed as increase in degradation of ERalpha incubated for 24 hrs by In-Cell Western assay relative to control	2019	Journal of medicinal chemistry, 12-26, Volume: 62, Issue:24	Design and Synthesis of Basic Selective Estrogen Receptor Degraders for Endocrine Therapy Resistant Breast Cancer.
AID1251784	Antiproliferative activity against human MCF7 cells	2015	Journal of medicinal chemistry, Oct-22, Volume: 58, Issue:20	Optimization of a Novel Binding Motif to (E)-3-(3,5-Difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic Acid (AZD9496), a Potent and Orally Bioavailable Selective Estrogen Receptor Downregu
AID1431903	Induction of ERalpha degradation in tamoxifen-sensitive human MCF7:WS8 cells after 24 hrs by CellTag 700 staining based In-cell western assay	2017	Journal of medicinal chemistry, 02-23, Volume: 60, Issue:4	Novel Selective Estrogen Receptor Downregulators (SERDs) Developed against Treatment-Resistant Breast Cancer.
AID269781	Antagonist activity assessed as inhibition of estrogen-stimulated uterine weight gain in ovariectomized mouse at 10 mg/kg, sc	2006	Bioorganic & medicinal chemistry letters, Aug-01, Volume: 16, Issue:15	Discovery of thiochroman derivatives bearing a carboxy-containing side chain as orally active pure antiestrogens.
AID1681439	Antitumor activity against human MC7 cells xenografted in CB17 SCID mouse assessed as tumor regression at 5 mg, po administered via gavage three times a week for 21 days	2020	Journal of medicinal chemistry, 12-10, Volume: 63, Issue:23	Discovery of AZD9833, a Potent and Orally Bioavailable Selective Estrogen Receptor Degrader and Antagonist.
AID1690974	Selective estrogen receptor alpha degrader activity in human MCF7 cells assessed as down regulation of ERalpha expression at 1 uM measured after 4 hrs in presence of protease inhibitor MG-132 by Western blot analysis	2020	European journal of medicinal chemistry, Apr-15, Volume: 192	Development of bivalent triarylalkene- and cyclofenil-derived dual estrogen receptor antagonists and downregulators.
AID1629292	Antiproliferative activity against human MCF7 cells after 5 days by coulter counter analysis	2016	Journal of medicinal chemistry, 09-08, Volume: 59, Issue:17	Fulvestrant-3 Boronic Acid (ZB716): An Orally Bioavailable Selective Estrogen Receptor Downregulator (SERD).
AID473421	Down regulation of ERalpha expression in human MCF7 cell nuclear fraction at 1 uM after 16 hrs by Western blotting	2010	Journal of medicinal chemistry, Apr-22, Volume: 53, Issue:8	Characterization of the pharmacophore properties of novel selective estrogen receptor downregulators (SERDs).
AID183163	Antagonist effect as ability to suppress uterine stimulatory EE2 effect in immature female rats at 10.0 mg/kg dose	2003	Bioorganic & medicinal chemistry letters, Dec-15, Volume: 13, Issue:24	B-ring unsaturated estrogens: biological evaluation of 17alpha-Dihydroequilein and novel B-Nor-6-thiaequilenins as tissue selective estrogens.
AID1690957	Displacement of fluorescent-labelled E2 from recombinant human GST-tagged ERbeta by LanthaScreen TR-FRET assay	2020	European journal of medicinal chemistry, Apr-15, Volume: 192	Development of bivalent triarylalkene- and cyclofenil-derived dual estrogen receptor antagonists and downregulators.
AID271237	Bioavailability in Sprague-Dawley rat	2006	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 16, Issue:18	Newly discovered orally active pure antiestrogens.
AID1559003	Drug concentration in C57BL/6 mouse brain at 5 mg, sc measured after 2 hrs by LC/MS-MS analysis	2019	Journal of medicinal chemistry, 12-26, Volume: 62, Issue:24	Design and Synthesis of Basic Selective Estrogen Receptor Degraders for Endocrine Therapy Resistant Breast Cancer.
AID1385759	Antiproliferative activity against human MCF7 cells assessed as cell proliferation after 6 days by MTT assay relative to control	2018	ACS medicinal chemistry letters, Aug-09, Volume: 9, Issue:8	New Class of Selective Estrogen Receptor Degraders (SERDs): Expanding the Toolbox of PROTAC Degrons.
AID1559001	Plasma concentration in C57BL/6 mouse at 5 mg, sc measured after 2 hrs by LC/MS-MS analysis	2019	Journal of medicinal chemistry, 12-26, Volume: 62, Issue:24	Design and Synthesis of Basic Selective Estrogen Receptor Degraders for Endocrine Therapy Resistant Breast Cancer.
AID1572971	Induction of ERalpha degradation in in human T47D cells assessed as reduction in ER protein level at 30 nM after 1 to 24 hrs by Western blot analysis relative to control	2019	Journal of medicinal chemistry, 02-14, Volume: 62, Issue:3	Discovery of ERD-308 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Estrogen Receptor (ER).
AID1443584	In vivo induction of ERalpha degradation in human MCF7 cells xenografted in immunocompromised nude mouse assessed as inhibition of ERalpha protein levels at at 250 mg/kg, sc administered once per week for 108 days measured at 24 hrs post last dose by ELIS	2017	Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7	Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ERα+ Breast Cancer.
AID271231	Antagonist effect on estrogen activity assessed as inhibition of estrogen-stimulated uterine weight gain in ovariectomized mouse at 10 mg/kg, po	2006	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 16, Issue:18	Newly discovered orally active pure antiestrogens.
AID1594514	Selective estrogen receptor down-regulator activity at FLAG-tagged ERalpha (unknown origin) expressed in HEK293 cells assessed as induction of ERalpha degradation by measuring dissociation constant for degradation by luciferase reporter gene assay relativ	2019	Bioorganic & medicinal chemistry, 05-15, Volume: 27, Issue:10	Structure-activity relationship study of estrogen receptor down-regulators with a diphenylmethane skeleton.
AID70324	Antagonist effect on transcriptional activation in MCF-7 cells expressing estrogen receptor alpha	2000	Bioorganic & medicinal chemistry letters, Jan-17, Volume: 10, Issue:2	Synthesis and estrogenic activities of novel 7-thiosubstituted estratriene derivatives.
AID728186	Antagonist activity at ERalpha receptor in human MCF7 cells assessed as inhibition of cell growth after 6 days by crystal violet staining method	2013	Journal of medicinal chemistry, Apr-11, Volume: 56, Issue:7	Synthesis of novel estrogen receptor antagonists using metal-catalyzed coupling reactions and characterization of their biological activity.
AID1228309	AUC in 17-beta estradiol pellets supplemented nu/nu mouse xenografted with tamoxifen-resistant human MCF7 cells at 200 mg/kg, sc administered 3 times per week for 4 weeks measured on day 28	2015	Journal of medicinal chemistry, Jun-25, Volume: 58, Issue:12	Identification of GDC-0810 (ARN-810), an Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts.
AID1385757	Displacement of [3H]estradiol from human full length ERalpha after 18 to 24 hrs by scintillation counting method	2018	ACS medicinal chemistry letters, Aug-09, Volume: 9, Issue:8	New Class of Selective Estrogen Receptor Degraders (SERDs): Expanding the Toolbox of PROTAC Degrons.
AID1559005	Cytotoxicity against human MCF7:WS8 monolayer cells assessed as reduction in tumor cell viability at 10 nM incubated for 10 days by celltiter-glo 3D cell viability assay	2019	Journal of medicinal chemistry, 12-26, Volume: 62, Issue:24	Design and Synthesis of Basic Selective Estrogen Receptor Degraders for Endocrine Therapy Resistant Breast Cancer.
AID625286	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatitis	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1829680	Antiproliferative activity against human MCF-7/TAMR-1 cells assessed as reduction in cell viability measured after 120 hrs by crystal violet staining based assayy
AID755345	Competitive inhibition of human recombinant soluble epoxide hydrolase using [3H]-tDPPO as substrate	2013	Bioorganic & medicinal chemistry letters, Jul-01, Volume: 23, Issue:13	Inhibition of soluble epoxide hydrolase by fulvestrant and sulfoxides.
AID1690975	Aqueous solubility of compound in water	2020	European journal of medicinal chemistry, Apr-15, Volume: 192	Development of bivalent triarylalkene- and cyclofenil-derived dual estrogen receptor antagonists and downregulators.
AID1829681	Antiproliferative activity against human MDA-MB-231 cells assessed as reduction in cell viability measured after 120 hrs by crystal violet staining based assay
AID1906872	Induction of ERalpha degradation in human MCF7 cells at 1 nM incubated for 2 to 4 hrs by Western blot analysis	2022	Journal of medicinal chemistry, 04-14, Volume: 65, Issue:7	Discovery of Thieno[2,3-
AID1690970	Antagonist activity at ERbeta (unknown origin) expressed in human U2OS cells assessed as inhibition of E2-induced transactivation measured after 21 hrs by dual luciferase reporter gene assay	2020	European journal of medicinal chemistry, Apr-15, Volume: 192	Development of bivalent triarylalkene- and cyclofenil-derived dual estrogen receptor antagonists and downregulators.
AID625282	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cirrhosis	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID499833	Antiestrogenic activity in human MCF7 cells assessed as decrease of ER-mediated PR expression at 100 uM by RT-PCR analysis in presence of estradiol	2010	Journal of medicinal chemistry, Aug-26, Volume: 53, Issue:16	Effects of 7-O substitutions on estrogenic and anti-estrogenic activities of daidzein analogues in MCF-7 breast cancer cells.
AID597271	Antiproliferative activity against human MCF7 cells expressing estrogen receptor incubated with 100 nM of estradiol and 0.07 nM of testosterone after 48 hrs by sulforhodamine B assay in presence of fetal bovine serum and NuSerum	2011	Journal of medicinal chemistry, May-26, Volume: 54, Issue:10	Biomimetic syntheses and antiproliferative activities of racemic, natural (-), and unnnatural (+) glyceollin I.
AID755348	Inhibition of human recombinant soluble epoxide hydrolase using (cyano(6-methoxy-naphthelen-2-yl)methyl trans-[(3-phenyl-oxiran-2-yl)methyl] carbonate) as substrate preincubated for 5 mins prior to substrate addition by fluorescence assay	2013	Bioorganic & medicinal chemistry letters, Jul-01, Volume: 23, Issue:13	Inhibition of soluble epoxide hydrolase by fulvestrant and sulfoxides.
AID1594508	Antagonist activity at FLAG-tagged ERalpha (unknown origin) expressed in HEK293 cells assessed as reduction in E2-induced ER-alpha-mediated transcriptional activity by luciferase reporter gene assay	2019	Bioorganic & medicinal chemistry, 05-15, Volume: 27, Issue:10	Structure-activity relationship study of estrogen receptor down-regulators with a diphenylmethane skeleton.
AID269790	AUC in Sprague-Dawley rat at 20 mg/kg, po	2006	Bioorganic & medicinal chemistry letters, Aug-01, Volume: 16, Issue:15	Discovery of thiochroman derivatives bearing a carboxy-containing side chain as orally active pure antiestrogens.
AID1535226	Antiproliferative activity against human MCF7 cells assessed as reduction in cell proliferation measured after 5 days by Cell-titer-Glo assay	2019	Bioorganic & medicinal chemistry letters, 02-01, Volume: 29, Issue:3	Selective estrogen receptor degraders with novel structural motifs induce regression in a tamoxifen-resistant breast cancer xenograft.
AID728175	Antagonist activity at LBD of ERalpha receptor in human HeLa cells assessed as blockade of SRC-1 binding to receptor at 100 nM after 20 to 24 hrs by luciferase reporter gene assay	2013	Journal of medicinal chemistry, Apr-11, Volume: 56, Issue:7	Synthesis of novel estrogen receptor antagonists using metal-catalyzed coupling reactions and characterization of their biological activity.
AID1779056	Downregulation of ERalpha expression in human MCF7 cells at 0.5 uM incubated for 24 hrs by Western blot assay	2021	European journal of medicinal chemistry, Oct-05, Volume: 221	Design and synthesis of novel benzothiophene analogs as selective estrogen receptor covalent antagonists against breast cancer.
AID1228207	Induction of estrogen receptor-alpha degradation in human MCF7 cells at 5.12 x 10'-13 to 10'-6 M after 4 hrs by in-cell western assay relative to control	2015	Journal of medicinal chemistry, Jun-25, Volume: 58, Issue:12	Identification of GDC-0810 (ARN-810), an Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts.
AID1829666	Displacement of fluorescent-labeled E2 from LBD of ERbeta (unknown origin) assessed as relative binding affinity by TR-FRET assay relative to control
AID1228305	Antitumor activity against tamoxifen-resistant human MCF7 cells xenografted in nu/nu mouse supplemented with 17-beta estradiol pellets assessed as tumor volume at 200 mg/kg, sc administered 3 times per week for 4 weeks measured twice weekly during compoun	2015	Journal of medicinal chemistry, Jun-25, Volume: 58, Issue:12	Identification of GDC-0810 (ARN-810), an Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts.
AID245769	Inhibition of ER-MDA-MB 231 breast cancer cell proliferation over 96 hr at 5 uM	2004	Bioorganic & medicinal chemistry letters, Sep-20, Volume: 14, Issue:18	Synthesis and biological evaluation of stilbene-based pure estrogen antagonists.
AID468382	Antagonist activity at ERbeta in HEK293 cells assessed as inhibition of ERE-dependent luciferase expression at 1 uM	2009	Journal of medicinal chemistry, Nov-12, Volume: 52, Issue:21	Novel dehydroepiandrosterone derivatives with antiapoptotic, neuroprotective activity.
AID1658825	Induction of ERalpha degradation in human MCF7 cells after 4 hrs by FITC/Hoechst staining based immunofluorescence imaging analysis	2020	ACS medicinal chemistry letters, Jun-11, Volume: 11, Issue:6	Discovery of GNE-149 as a Full Antagonist and Efficient Degrader of Estrogen Receptor alpha for ER+ Breast Cancer.
AID755347	Inhibition of human recombinant soluble epoxide hydrolase	2013	Bioorganic & medicinal chemistry letters, Jul-01, Volume: 23, Issue:13	Inhibition of soluble epoxide hydrolase by fulvestrant and sulfoxides.
AID755445	Agonist activity at PXR (unknown origin) expressed in human HepG2 cells assessed as induction of CYP3A4 transactivation after 16 hrs by luciferase reporter gene assay	2013	Bioorganic & medicinal chemistry, Jul-15, Volume: 21, Issue:14	Development of time resolved fluorescence resonance energy transfer-based assay for FXR antagonist discovery.
AID1387899	Downregulation of estrogen receptor alpha protein levels in human MCF7 cell lysate at 1 uM after 24 hrs by Western blot analysis	2018	Journal of medicinal chemistry, 01-25, Volume: 61, Issue:2	Lead Optimization of Benzoxepin-Type Selective Estrogen Receptor (ER) Modulators and Downregulators with Subtype-Specific ERα and ERβ Activity.
AID271234	AUC in Sprague-Dawley rat at 10 mg/kg, iv	2006	Bioorganic & medicinal chemistry letters, Sep-15, Volume: 16, Issue:18	Newly discovered orally active pure antiestrogens.
AID1559009	Cytotoxicity against human T47D monolayer cells harboring D538G mutant assessed as reduction in tumor cell viability at 10 nM incubated for 10 days by celltiter-glo 3D cell viability assay	2019	Journal of medicinal chemistry, 12-26, Volume: 62, Issue:24	Design and Synthesis of Basic Selective Estrogen Receptor Degraders for Endocrine Therapy Resistant Breast Cancer.
AID304033	Inhibition of 300 nM estradiol induced stimulation of DNA synthesis in human MLS cells assessed as ratio of treated to untreated control at 1.1 uM after 48 hrs by [3H]thymidine incorporation assay	2007	Journal of medicinal chemistry, Dec-13, Volume: 50, Issue:25	Synthesis and evaluation of the antiproliferative activities of derivatives of carboxyalkyl isoflavones linked to N-t-Boc-hexylenediamine.
AID755346	Reversible inhibition of human recombinant soluble epoxide hydrolase assessed as residual enzyme activity at 10 uM after 15 mins relative to control	2013	Bioorganic & medicinal chemistry letters, Jul-01, Volume: 23, Issue:13	Inhibition of soluble epoxide hydrolase by fulvestrant and sulfoxides.
AID1690978	Antiproliferative activity against human MCF7 cells assessed as cell mass at 50 nM measured after 72 hrs by crystal violet staining based assay relative to control	2020	European journal of medicinal chemistry, Apr-15, Volume: 192	Development of bivalent triarylalkene- and cyclofenil-derived dual estrogen receptor antagonists and downregulators.
AID597277	Antiproliferative activity against human LNCAP cells expressing androgen receptor incubated with 0.6 nM of estradiol and 0.7 nM of testosterone after 48 hrs by sulforhodamine B assay	2011	Journal of medicinal chemistry, May-26, Volume: 54, Issue:10	Biomimetic syntheses and antiproliferative activities of racemic, natural (-), and unnnatural (+) glyceollin I.
AID368186	Down regulation of estrogen receptor alpha expression in human MCF7 cells at 100 nM after 24 hrs by immunofluorescence staining	2009	Journal of medicinal chemistry, Feb-12, Volume: 52, Issue:3	Effect of fluorination on the pharmacological profile of 11beta isomers of fulvestrant in breast carcinoma cells.
AID1594512	Selective estrogen receptor down-regulator activity at FLAG-tagged ERalpha (unknown origin) expressed in HEK293 cells assessed as induction of ERalpha degradation at 1 uM in presence of 0.1 to 10 uM proteasome inhibitor bortezomib by luciferase reporter g	2019	Bioorganic & medicinal chemistry, 05-15, Volume: 27, Issue:10	Structure-activity relationship study of estrogen receptor down-regulators with a diphenylmethane skeleton.
AID269782	Antagonist activity assessed as inhibition of estrogen-stimulated uterine weight gain in ovariectomized mouse at 10 mg/kg, po	2006	Bioorganic & medicinal chemistry letters, Aug-01, Volume: 16, Issue:15	Discovery of thiochroman derivatives bearing a carboxy-containing side chain as orally active pure antiestrogens.
AID1228231	Cytotoxicity against human MCF7 cells assessed as cell viability after 5 days by CellTiter-Glo assay	2015	Journal of medicinal chemistry, Jun-25, Volume: 58, Issue:12	Identification of GDC-0810 (ARN-810), an Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts.
AID1228303	Antitumor activity against tamoxifen-sensitive human MCF7 cells xenografted in nu/nu mouse supplemented with 17-beta estradiol pellets assessed as change in tumor volume at 200 mg/kg, sc administered 3 times per week for 4 weeks measured on day 28 (Rvb =	2015	Journal of medicinal chemistry, Jun-25, Volume: 58, Issue:12	Identification of GDC-0810 (ARN-810), an Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts.
AID1446051	Downregulation of human ERalpha in human MCF-7 cells after 24 hrs by in-cell Western immunoassay method	2017	Journal of medicinal chemistry, 07-27, Volume: 60, Issue:14	Adamantyl Antiestrogens with Novel Side Chains Reveal a Spectrum of Activities in Suppressing Estrogen Receptor Mediated Activities in Breast Cancer Cells.
AID1347110	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347106	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347118	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347113	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1296008	Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening	2020	SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1	Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1347117	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347424	RapidFire Mass Spectrometry qHTS Assay for Modulators of WT P53-Induced Phosphatase 1 (WIP1)	2019	The Journal of biological chemistry, 11-15, Volume: 294, Issue:46	Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens.
AID1347100	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID651635	Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression
AID1347122	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347124	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347121	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for control Hh wild type fibroblast cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347096	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347111	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347112	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347105	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347097	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347099	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347116	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347095	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347119	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347129	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347091	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347093	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347092	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347125	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347094	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347114	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347102	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347101	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347098	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347126	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347123	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347407	qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Pharmaceutical Collection	2020	ACS chemical biology, 07-17, Volume: 15, Issue:7	High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1347089	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1745845	Primary qHTS for Inhibitors of ATXN expression
AID1347425	Rhodamine-PBP qHTS Assay for Modulators of WT P53-Induced Phosphatase 1 (WIP1)	2019	The Journal of biological chemistry, 11-15, Volume: 294, Issue:46	Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens.
AID1347154	Primary screen GU AMC qHTS for Zika virus inhibitors	2020	Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49	Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347128	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347115	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347108	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347090	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347127	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347103	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347107	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347104	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347109	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1794808	Fluorescence-based screening to identify small molecule inhibitors of Plasmodium falciparum apicoplast DNA polymerase (Pf-apPOL).	2014	Journal of biomolecular screening, Jul, Volume: 19, Issue:6	A High-Throughput Assay to Identify Inhibitors of the Apicoplast DNA Polymerase from Plasmodium falciparum.
AID1794808	Fluorescence-based screening to identify small molecule inhibitors of Plasmodium falciparum apicoplast DNA polymerase (Pf-apPOL).
AID1346987	P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen	2019	Molecular pharmacology, 11, Volume: 96, Issue:5	A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1346986	P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen	2019	Molecular pharmacology, 11, Volume: 96, Issue:5	A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1346845	Human Estrogen receptor-alpha (3A. Estrogen receptors)	2003	Journal of medicinal chemistry, Apr-10, Volume: 46, Issue:8	De novo design, synthesis, and evaluation of novel nonsteroidal phenanthrene ligands for the estrogen receptor.
AID1346880	Human Estrogen receptor-beta (3A. Estrogen receptors)	2003	Journal of medicinal chemistry, Apr-10, Volume: 46, Issue:8	De novo design, synthesis, and evaluation of novel nonsteroidal phenanthrene ligands for the estrogen receptor.
AID1345880	Human GPER (G protein-coupled estrogen receptor)	2005	Endocrinology, Feb, Volume: 146, Issue:2	Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	255 (9.70)	18.2507
2000's	1062 (40.40)	29.6817
2010's	975 (37.09)	24.3611
2020's	337 (12.82)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Publication Type	This drug (%)	All Drugs (%)
Trials	207 (7.63%)	5.53%
Reviews	208 (7.67%)	6.00%
Case Studies	48 (1.77%)	4.05%
Observational	11 (0.41%)	0.25%
Other	2,238 (82.52%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (402)

Trial Overview

Trial	Phase	Enrollment	Study Type	Start Date	Status
An Open-label, Single Arm, Prospective, Multi-center, Tandem Two Stage Designed, Phase II Study to Evaluate the Efficacy of Fulvestrant in Women With Recurrent/Metastatic Estrogen Receptor Positive Gynecological Malignancies[NCT03926936]	Phase 2	200 participants (Anticipated)	Interventional	2019-03-13	Recruiting
An Open, Non-randomised Multicentre Phase II Study to Assess the Efficacy and Tolerability of a 250 mg Monthly Dose of i.m. Applied Fulvestrant for the Treatment of Recurrent or Metastatic Endometrial Carcinoma.[NCT00334295]	Phase 2	35 participants (Actual)	Interventional	2002-12-31	Completed
A Randomized, Open-Label, Parallel-Group, Multicentre, Phase II Study to Compare the Efficacy and Tolerability of Fulvestrant (FASLODEX™) 500 mg With Anastrozole (ARIMIDEX™) 1 mg as First Line Hormonal Treatment for Postmenopausal Women With Hormone Recep[NCT00274469]	Phase 2	205 participants (Actual)	Interventional	2006-02-06	Completed
A Phase III Randomized, Open-Label Study Evaluating Efficacy and Safety of Giredestrant Compared With Fulvestrant, Both Combined With a CDK4/6 Inhibitor, in Patients With Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer With Resistance to [NCT06065748]	Phase 3	1,050 participants (Anticipated)	Interventional	2023-12-11	Recruiting
A Phase Ib Dose Finding Study Assessing Safety and Activity of [177Lu]Lu-NeoB in Combination With Ribociclib and Fulvestrant in Participants With Estrogen Receptor Positive, Human Epidermal Growth Factor Receptor-2 Negative and Gastrin Releasing Peptide R[NCT05870579]	Phase 1	45 participants (Anticipated)	Interventional	2023-11-13	Recruiting
A Phase 2 Study to Evaluate the Safety and Efficacy of Lerociclib in Participants With Advanced Breast Cancer[NCT05085002]	Phase 2	100 participants (Actual)	Interventional	2021-12-21	Terminated(stopped due to The study is being closed based on corporate changes at EQRx and is not related to any efficacy or safety issues with lerociclib.)
Phase 2a Study of ZW25 in Combination With Palbociclib Plus Fulvestrant[NCT04224272]	Phase 2	51 participants (Actual)	Interventional	2020-06-10	Active, not recruiting
A Phase III Study to Evaluate the Efficacy and Safety of SHR6390 in Combination With Fulvestrant Versus Placebo Combined With Fulvesrant in Patients With HR Positive and HER2 Negative Recurrent/Metastatic Breast Cancer[NCT03927456]	Phase 3	357 participants (Anticipated)	Interventional	2019-06-13	Active, not recruiting
Study to Evaluate the Efficacy and Safety of Famitinib Plus SHR6390 and Endocrine Therapy in the Treatment of Hormone Receptor-positive, Human Epidermal Growth Factor Receptor 2-negative Advanced Breast Cancer[NCT05176080]	Phase 1/Phase 2	65 participants (Anticipated)	Interventional	2021-12-08	Active, not recruiting
A Pilot Study of AZD5363 for Patients With Advanced Solid Tumors Harboring Mutations in AKT1, AKT2, or AKT3[NCT03310541]	Phase 1	12 participants (Actual)	Interventional	2017-10-11	Completed
A Phase 1b Study of ARQ 751 as a Single Agent or in Combination With Other Anti-cancer Agents in Adult Subjects With Advanced Solid Tumors With PIK3CA / AKT / PTEN Mutations[NCT02761694]	Phase 1	78 participants (Actual)	Interventional	2016-06-26	Terminated(stopped due to Business Reasons)
Phase II Trial of Primary Endocrine Therapy With Combination of Fulvestrant or an Aromatase Inhibitor and Palbociclib in Elderly Patients With Hormone Responsive Breast Cancer Who Have Inoperable Tumor Or Operable Tumor But Cannot Undergo Surgery Due to F[NCT02760030]	Phase 2	37 participants (Anticipated)	Interventional	2017-02-16	Recruiting
Fulvestrant With or Without AZD6244, a Mitogen-Activated Protein Kinase Kinase (MEK) ½ Inhibitor, in Advanced Stage Breast Cancer Progressing After Aromatase Inhibitor: A Randomized Placebo-Controlled Double-Blind Phase II Trial[NCT01160718]	Phase 2	46 participants (Actual)	Interventional	2010-08-31	Completed
A Phase Ib/II Study of Debio 1347 Plus Fulvestrant in Patients With FGFR-Amplified Endocrine Receptor Positive Metastatic Breast Cancer[NCT03344536]	Phase 1/Phase 2	10 participants (Actual)	Interventional	2017-11-10	Completed
Phase II Study of Faslodex ? in Recurrent/Metastatic Endometrial Carcinoma[NCT00006903]	Phase 2	67 participants (Actual)	Interventional	2004-08-30	Active, not recruiting
Sensitivity Detection and Drug Resistance Mechanism of Breast Cancer Therapeutic Drugs Based on Organ-like Culture[NCT03925233]		300 participants (Anticipated)	Observational	2019-01-02	Enrolling by invitation
Randomized Phase II Study OF Goserelin (G) Plus Fulvestrant (F) vs. G Plus Anastrozole (A)vs. G Alone for HR+, Tamoxifen Pretreated, Premenopausal Woman[NCT01266213]	Phase 2	147 participants (Anticipated)	Interventional	2010-12-31	Active, not recruiting
An Open-Label, Phase I/II, Dose-Escalation Study Evaluating the Safety and Tolerability of GDC-0032 in Patients With Locally Advanced or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma and in Combination With Endocrine Therapy in Patients With Locally A[NCT01296555]	Phase 1	686 participants (Actual)	Interventional	2011-03-16	Completed
A Dose Escalation and Expansion Study of the Safety and Pharmacokinetics of XL102 as Single-Agent and Combination Therapy in Subjects With Inoperable Locally Advanced or Metastatic Solid Tumors[NCT04726332]	Phase 1	373 participants (Anticipated)	Interventional	2021-02-10	Recruiting
A Prospective Study on Efficacy and Safety of Anlotinib Combined With Fulvestrant in Patients With HR-positive and HER2-negative, Secondary Endocrine-resistant, Locally Advanced or Metastatic Breast Cancer[NCT05075512]	Phase 2	40 participants (Anticipated)	Interventional	2021-09-01	Recruiting
An Open Label, Randomised, Pre-surgical, Pharmacodynamics Study to Compare the Biological Effects of AZD9496 Versus Fulvestrant in Postmenopausal Women With ER Positive HER-2 Negative Primary Breast Cancer[NCT03236974]	Phase 1	49 participants (Actual)	Interventional	2017-10-05	Completed
NANT Ovarian Cancer Vaccine: Combination Immunotherapy in Subjects With Epithelial Ovarian Cancer Who Have Progressed on or After Standard-of-care (SoC) Therapy[NCT03197584]	Phase 1/Phase 2	0 participants (Actual)	Interventional	2017-12-31	Withdrawn(stopped due to Trial not initiated)
Clinical Study of Fulvestrant Combined With Chidamide in the Treatment of Hormone Receptor-positive Advanced Breast Cancer Resistant to Cyclin-dependent Kinases（CDK）4/6 Inhibitors[NCT05191914]	Phase 4	20 participants (Anticipated)	Interventional	2022-02-07	Not yet recruiting
NANT Non-small Cell Lung Cancer (NSCLC) Vaccine: Combination Immunotherapy in Subjects With NSCLC Who Have Progressed After Treatment With Programmed Cell Death Protein 1 (PD-1)/Programmed Death-ligand 1 (PD-L1) Inhibitors[NCT03169738]	Phase 1/Phase 2	0 participants (Actual)	Interventional	2018-02-28	Withdrawn(stopped due to Trial not initiated)
A Randomized Trial With Factorial Design Comparing Fulvestrant ± Lapatinib ± Aromatase Inhibitor in Metastatic Breast Cancer Progressing After Aromatase Inhibitor Therapy[NCT02394496]	Phase 3	396 participants (Anticipated)	Interventional	2007-11-30	Recruiting
A Phase II, Multicenter, Randomized Study To Compare The Efficacy Of Venetoclax Plus Fulvestrant Versus Fulvestrant In Women With Estrogen Receptor-Positive, Her2-Negative Locally Advanced Or Metastatic Breast Cancer Who Experienced Disease Recurrence Or [NCT03584009]	Phase 2	103 participants (Actual)	Interventional	2018-09-06	Terminated(stopped due to Sponsor's decision, no safety concerns.)
Phase 2 Study of Alpelisib and Fulvestrant for PIK3CA-mutated Estrogen Receptor (ER)-Positive Endometrioid Endometrial Cancers[NCT05154487]	Phase 2	51 participants (Anticipated)	Interventional	2024-01-30	Not yet recruiting
A Randomized, 2-Arm, Open-Label, Ph-II Study of Abemaciclib Combined With ET w/ or w/o CT With Paclitaxel as 1L in Patients With Unresectable Locally Advanced or Metastatic HR(+)/HER2(-) BC With Aggressive Disease Criteria[NCT04603183]	Phase 2	160 participants (Anticipated)	Interventional	2021-06-02	Recruiting
A Phase III, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Inavolisib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, He[NCT04191499]	Phase 2/Phase 3	325 participants (Anticipated)	Interventional	2020-01-29	Recruiting
Randomized Phase III Study of Fulvestrant as Maintenance Therapy After First-line Chemotherapy in HER2 Negative Postmenopausal Metastatic Breast Cancer Patients[NCT02383030]	Phase 3	156 participants (Anticipated)	Interventional	2015-11-30	Recruiting
A Phase 1b/2 Study of GS-5829 in Combination With Fulvestrant or Exemestane in Subjects With Advanced Estrogen Receptor Positive, HER2 Negative-Breast Cancer[NCT02983604]	Phase 1/Phase 2	14 participants (Actual)	Interventional	2017-01-10	Terminated
Phase I Study of the Combination of MLN9708 and Fulvestrant in Patients With Advanced Estrogen Receptor Positive Breast Cancer[NCT02384746]	Phase 1	9 participants (Actual)	Interventional	2015-06-02	Terminated(stopped due to Low accrual)
A Randomized, Double-blind, Placebo-controlled, Phase III Clinical Trial of GB491 Combined With Fulvestrant in Subjects With HR+, HER2- Locally Advanced or Metastatic Breast Cancer Who Have Progressed on Prior Endocrine Therapy[NCT05054751]	Phase 3	270 participants (Anticipated)	Interventional	2021-09-10	Recruiting
A Phase III Study to Evaluate the Efficacy and Safety of XZP-3287 in Combination With Fulvestrant Versus Placebo Combined With Fulvestrant in Patients With HR Positive and HER2 Negative Recurrent/Metastatic Breast Cancer[NCT05077449]	Phase 3	300 participants (Anticipated)	Interventional	2021-11-16	Recruiting
Multicentre, International Neoadjuvant Randomized Double-blind Trial Comparing Fulvestrant® to a Combination of Fulvestrant® and Palbociclib (CDK 4/6 Inhibitor) in Patients With Operable Luminal Breast Cancer Responding to Fulvestrant®[NCT03447132]	Phase 3	354 participants (Actual)	Interventional	2017-12-20	Completed
The Study of Goserelin Plus Fulvestrant Comparing With Goserelin Plus Anastrozole for Advanced Breast Cancer[NCT02072512]	Phase 2	180 participants (Anticipated)	Interventional	2014-01-31	Recruiting
A Phase 1 Trial of MK-2206 in Combination With Anastrozole, Fulvestrant, or Anastrozole Plus Fulvestrant in Postmenopausal Women With Estrogen Receptor Positive Metastatic Breast Cancer[NCT01344031]	Phase 1	31 participants (Actual)	Interventional	2011-04-21	Completed
A Phase I/II Dose Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK525762 in Combination With Fulvestrant in Subjects With Hormone Receptor-positive/HER2-negative (HR+/HER2-) Advanced[NCT02964507]	Phase 1	124 participants (Actual)	Interventional	2017-02-02	Terminated(stopped due to This study has been terminated due to meeting protocol defined futility.)
Comparative Effectiveness of Palbociclib Plus Aromatase Inhibitor Versus Fulvestrant Alone as Initial Endocrine Therapy for HR+/HER2- Advanced Breast Cancer in Chinese Clinical Practice: a Real-world Study[NCT05000736]		600 participants (Anticipated)	Observational	2021-09-01	Recruiting
PHASE 1/2A DOSE ESCALATION, FINDING AND EXPANSION STUDY EVALUATING SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS AND ANTI TUMOR ACTIVITY OF PF-07104091 AS A SINGLE AGENT AND IN COMBINATION THERAPY[NCT04553133]	Phase 1/Phase 2	320 participants (Anticipated)	Interventional	2020-09-16	Recruiting
FACT: Anastrozole Monotherapy Versus Maximal Oestrogen Blockade With Anastrozole and Fulvestrant Combination Therapy; an Open Randomized, Comparative, Phase III Multicentre Study in Postmenopausal Women With Hormone Receptor Positive Breast Cancer in Firs[NCT00256698]	Phase 3	514 participants (Actual)	Interventional	2004-01-31	Completed
RETENTION: An Open-Label Phase 2 Trial of InteRlEukin (5) InhibiTion for the prEveNTION of Alpelisib Rash in Metastatic PIK3CA-mutant Hormone-Receptor Positive Breast Cancer[NCT05966584]	Phase 2	63 participants (Anticipated)	Interventional	2023-07-06	Recruiting
Endocrine Therapy With or Without Inhibition of EGF and HER2 Growth Factor Receptors: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Fulvestrant With or Without Lapatinib (GW572016) for Postmenopausal Women With Hormone Receptor Positiv[NCT00390455]	Phase 3	295 participants (Actual)	Interventional	2006-09-15	Completed
Phase III Randomized Trial of Anastrozole Versus Anastrozole and Fulvestrant as First Line Therapy for Post Menopausal Women With Metastatic Breast Cancer[NCT00075764]	Phase 3	695 participants (Actual)	Interventional	2004-04-30	Completed
A Phase II Study of Pembrolizumab Plus Fulvestrant in Hormone Receptor Positive, HER-2 Negative Advanced/Metastatic Breast Cancer Patients: Big Ten Cancer Research Consortium BTCRC-BRE16-042[NCT03393845]	Phase 2	47 participants (Actual)	Interventional	2018-01-29	Active, not recruiting
"Neo-Adjuvant Treatment With the CDK4,6 Inhibitor Palbociclib in HER2-positive and ER-positive Breast Cancer: Effect on Ki67 and Apoptosis Before, During and After Treatment "[NCT02530424]	Phase 2	102 participants (Actual)	Interventional	2015-05-31	Completed
Phase I Trial of Abexinostat Combined With Palbociclib and Fulvestrant in Patients With Antiestrogen Refractory ER+, HER2- Breast Cancer and Gynecological Metastatic Tumors[NCT04498520]	Phase 1	0 participants (Actual)	Interventional	2021-03-31	Withdrawn(stopped due to Funding)
A ctDNA Screening Program in Patients With HR+, HER2- Metastatic Breast Cancer for Detection of High-risk Relapse Patients on Any CDK4/6 Inhibitor and a Randomised Phase II Study Comparing Alpelisib Combined With Fulvestrant to Ribociclib Combined With Fu[NCT05625087]	Phase 2	162 participants (Anticipated)	Interventional	2023-10-19	Recruiting
A Dose-confirming Study of CFI-402257 as a Single Agent in Advanced Solid Tumors and in Combination With Fulvestrant in Patients With ER+/HER2- Advanced Breast Cancer After Disease Progression on Prior CDK4/6 and Endocrine Therapy[NCT05251714]	Phase 1/Phase 2	44 participants (Anticipated)	Interventional	2022-05-27	Recruiting
"A Randomized Phase III Trial of Trastuzumab + ALpelisib +/- Fulvestrant Versus Trastuzumab + Chemotherapy in Patients With PIK3CA Mutated Previously Treated HER2+ Advanced BrEasT Cancer. ALPHABET Study."[NCT05063786]	Phase 3	300 participants (Anticipated)	Interventional	2021-09-14	Recruiting
An Open-Label, Single Arm, Phase II Trial to Evaluate the Efficacy of 500mg Fulvestrant (Faslodex) in ESR1 Mutated Postmenopausal Women With Hormone Receptor Positive, HER2 Negative Locally Advanced or Metastatic Breast Cancer After Previous Aromatase Inh[NCT03202862]	Phase 2	50 participants (Anticipated)	Interventional	2017-07-01	Not yet recruiting
Phase III Trial Comparing Efficacy and Tolerance of Fulvestrant for 3 Years (y) Combined With Anastrozole 5 y Versus Anastrozole 5 y as Adjuvant Hormonotherapy in Postmenopausal With Early Breast Cancer and Positive Hormone Receptors[NCT00543127]	Phase 3	870 participants (Actual)	Interventional	2007-11-30	Terminated(stopped due to Unjustified decision of company that funded the trial.)
Palbociclib in Combination With Fulvestrant or Tamoxifen as Treatment for Hormone Receptor Positive Metastatic Breast Cancer Previously Exposed to Inhibitors of the PI3K Pathway: A Phase II Study With Pharmacodynamics Markers[NCT02384239]	Phase 2	70 participants (Actual)	Interventional	2015-10-19	Completed
A Phase II Study to Evaluate Efficacy, Safety and Tolerability of KN026 in Combination With Palbociclib and Fulvestrant in Patients With Locally Advanced HER2-positive Breast Cancer[NCT04778982]		4 participants (Actual)	Observational	2022-05-25	Terminated(stopped due to Difficulty in completing enrollment within the planned time)
A Biomarker Study of Palbociclib + Fulvestrant for Second, and Third Line of Postmenopausal Women With hr+/her2- Advanced Breast Cancer (PALPETBIO)[NCT03560856]	Phase 2	54 participants (Anticipated)	Interventional	2018-06-27	Not yet recruiting
EMBER-3: A Phase 3, Randomized, Open-Label Study of Imlunestrant, Investigator's Choice of Endocrine Therapy, and Imlunestrant Plus Abemaciclib in Patients With Estrogen Receptor Positive, HER2 Negative Locally Advanced or Metastatic Breast Cancer Previou[NCT04975308]	Phase 3	860 participants (Anticipated)	Interventional	2021-10-04	Recruiting
A Phase Ib/II Study of LEE011 in Combination With Fulvestrant and BYL719 or BKM120 in the Treatment of Postmenopausal Women With Hormone Receptor Positive, HER2 Negative Locally Recurrent or Advanced Metastatic Breast Cancer[NCT02088684]	Phase 1	70 participants (Actual)	Interventional	2014-05-19	Completed
A Phase 2, Randomized, Double-Blind, Multicenter Study of Fulvestrant With and Without Entinostat in Postmenopausal Women With Hormone Receptor-Positive Advanced Breast Cancer[NCT02115594]	Phase 2	0 participants (Actual)	Interventional	2014-04-30	Withdrawn(stopped due to Internal decision)
A Phase 1 Study of the CDK4/6 Inhibitor Ribociclib (LEE011) in Combination With the PD-1 Inhibitor PDR001 in Patients With Metastatic Hormone Receptor-positive Breast Cancer and Metastatic Ovarian Cancer[NCT03294694]	Phase 1	33 participants (Actual)	Interventional	2017-11-08	Terminated(stopped due to Safety Implications)
An Open, Single-center, Exploratory Cohort Study of Chidamide in Combination With Endocrine in Maintenance Therapy After First-line Chemotherapy for HR+/HER2- Breast Cancer[NCT05890287]		60 participants (Anticipated)	Interventional	2023-05-16	Recruiting
Treatment Patterns and Clinical Outcomes Among Patients Receiving Palbociclib Combinations for Hormone Receptor Positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Advanced/Metastatic Breast Cancer in the Arabian Gulf Region Like Saud[NCT04916509]		258 participants (Actual)	Observational	2021-09-13	Completed
A Phase II Open Label Trial of Neo-Adjuvant Abemaciclib With Fulvestrant in Patients Who Develop Localized Recurrence While on Adjuvant Endocrine Therapy With Molecular Evidence of Endocrine Resistance[NCT04305236]	Phase 2	1 participants (Actual)	Interventional	2020-07-23	Terminated(stopped due to Halted due to study funding)
Evaluation of the Antitumor Activity, Safety, and Pharmacokinetic Profile of FCN-437c in Combination With Fulvestrant or Letrozole + Goserelin in Female Patients With ER+, HER2- Advanced Breast Cancer[NCT05004142]	Phase 2	70 participants (Anticipated)	Interventional	2020-06-30	Recruiting
Trial of Tucidinostat in Combination With Fulvestrant in Patients With Hormone-receptor Positive Advanced Breast Cancer[NCT04999540]	Phase 2	73 participants (Anticipated)	Interventional	2021-11-01	Not yet recruiting
A Phase 1a/1b Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of the CDK4 Inhibitor BGB-43395, Alone or as Part of Combination Therapies in Patients With Metastatic HR+/HER2- Breast Canc[NCT06120283]	Phase 1	79 participants (Anticipated)	Interventional	2023-12-01	Recruiting
Role of Fulvestrant in The Treatment of Metastatic Breast Cancer in Premenopausal Women[NCT03591549]	Phase 4	30 participants (Anticipated)	Interventional	2018-08-01	Not yet recruiting
Treatment of Canadian Men and Pre/Postmenopausal Women With ER+ Advanced Breast Cancer in the Real-World Setting With Hormone Therapy ± Targeted Therapy[NCT02753686]		440 participants (Actual)	Observational [Patient Registry]	2016-03-15	Completed
A Phase 1/2a Study to Evaluate the Tolerability, Safety, Pharmacokinetics and Efficacy of BPI-1178 Alone in Advanced Solid Tumor and of BPI-1178 in Combination With Endocrine Therapy in Advanced HR+/HER2- Breast Cancer[NCT04282031]	Phase 1/Phase 2	224 participants (Anticipated)	Interventional	2020-06-15	Recruiting
A Phase I, Open-label, Multicentre, Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of AZD2014 Administered Orally in Combination With Intramuscular (IM) Fulvestrant to Patients With Estrogen Receptor Positive (ER+) Adv[NCT01597388]	Phase 1	99 participants (Actual)	Interventional	2012-05-08	Active, not recruiting
An International, Randomized, Double-blind, Placebo-controlled, Phase 2 Study of AMG 479 With Exemestane or Fulvestrant in Postmenopausal Women With Hormone Receptor Positive Locally Advanced or Metastatic Breast Cancer[NCT00626106]	Phase 2	156 participants (Actual)	Interventional	2008-03-31	Completed
Phase II Study to Assess Efficacy, Safety & Immunological Biomarker of Anti PD-L1 Antibody + Anti CTLA-4 Antibody in Combination With Hormone Therapy in Patients With Hormone Receptor Positive HER2-negative Recurrent or Metastatic Breast Cancer[NCT03430466]	Phase 2	1 participants (Actual)	Interventional	2017-06-22	Terminated(stopped due to Recruiting was not possible)
A Prospective Single-center Randomized Phase 2 Trial Comparing Docetaxel Plus Fulvestrant With Docetaxel in Postmenopausal, Hormone-receptor Positive and HER2-negative Metastatic Breast Cancer[NCT02137083]	Phase 2	22 participants (Actual)	Interventional	2014-04-30	Completed
An Open-label, Multi-center, Randomized Phase II Study of Fulvestrant Anastrozole Combination Versus Anastrozole Alone in Patients With Luminal A-like Postmenopausal Advanced Breast Cancer[NCT02140437]	Phase 2	0 participants (Actual)	Interventional	2014-03-31	Withdrawn(stopped due to The progress of enrollment is too slow.)
A Trial of Endocrine Response in Women With Invasive Lobular Breast Cancer[NCT02206984]	Phase 2	201 participants (Anticipated)	Interventional	2015-09-30	Recruiting
Patterns of Treatment and Outcome of Palbociclib Plus Endocrine Therapy in Hormone Receptor-positive (HR+)/HER2 Receptor-negative (HER2-) Metastatic Breast Cancer (MBC): a Real World Multicentre Italian Study[NCT04524728]		191 participants (Actual)	Observational [Patient Registry]	2016-12-31	Completed
Phase II Trial of Fulvestrant and Bevacizumab in Patients With Metastatic Breast Cancer Previously Treated With an Aromatase Inhibitor[NCT00423917]	Phase 2	36 participants (Actual)	Interventional	2007-08-31	Completed
SERENA-2: A Randomised, Open-Label, Parallel-Group, Multicentre Phase 2 Study Comparing the Efficacy and Safety of Oral AZD9833 Versus Fulvestrant in Women With Advanced ER-Positive HER2-Negative Breast Cancer[NCT04214288]	Phase 2	240 participants (Actual)	Interventional	2020-04-22	Active, not recruiting
A Randomized Phase II Trial of Combination Anastrozole (NSC #719344) Plus ZD1839 (Iressa, NSC #715055, IND #61187) and of Combination Fulvestrant (NSC #719276) Plus ZD1839 in the Treatment of Postmenopausal Women With Hormone Receptor-Positive Metastatic [NCT00057941]	Phase 2	148 participants (Actual)	Interventional	2003-09-30	Completed
A Phase 1 Study of SY-1365, a Selective CDK7 Inhibitor, in Adult Patients With Advanced Solid Tumors[NCT03134638]	Phase 1	107 participants (Actual)	Interventional	2017-05-12	Terminated(stopped due to Business Decision)
A Phase 1 Trial of BKM 120, a Novel Oral Selective Phosphatidylinositol-3-kinase (PI3K) Inhibitor, in Combination With Fulvestrant in Postmenopausal Women With Estrogen Receptor Positive Metastatic Breast Cancer[NCT01339442]	Phase 1	31 participants (Actual)	Interventional	2011-11-14	Completed
Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) Trial: Adaptive Clinical Treatment (ACT)[NCT05238831]	Early Phase 1	25 participants (Anticipated)	Interventional	2023-12-01	Not yet recruiting
A Phase IA, Multicenter, Open-label Dose Escalation Study of Oral BYL719, in Adult Patients With Advanced Solid Malignancies, Whose Tumors Have an Alteration of the PIK3CA Gene[NCT01219699]	Phase 1	221 participants (Actual)	Interventional	2010-10-05	Completed
First-in-Human Study of STX-478, a Mutant-Selective PI3Kα Inhibitor as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors[NCT05768139]	Phase 1/Phase 2	220 participants (Anticipated)	Interventional	2023-04-17	Recruiting
A Single Arm Phase 1/2 Trial of Abemaciclib + VS-6766 + Fulvestrant in Metastatic HR+/HER2- Breast Cancer[NCT05608252]	Phase 1/Phase 2	63 participants (Anticipated)	Interventional	2023-02-23	Recruiting
A Phase Ib/III, Open-label, Randomised Study of Capivasertib Plus CDK4/6 Inhibitors and Fulvestrant Versus CDK4/6 Inhibitors and Fulvestrant in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced, Unresectable [NCT04862663]	Phase 3	850 participants (Anticipated)	Interventional	2021-05-10	Recruiting
REVERT- Breast Cancer: Phase 1b/2 Study of the Addition of STAT3 Inhibitor TTI-101 to Reverse Resistance to Palbociclib or Ribociclib Plus Aromatase Inhibitor or Fulvestrant Therapy for Metastatic Hormone Receptor-Positive and HER2-Negative Breast Cancer[NCT05384119]	Phase 1/Phase 2	53 participants (Anticipated)	Interventional	2023-01-09	Recruiting
A Phase IB/II to Evaluate Efficacy and Safety of SHR6390 in Combination With Letrozole or Anastrozole or Fulvestrant in Patients With HR Positive and HER2 Negative Recurrent/Metastatic Breast Cancer[NCT03481998]	Phase 1/Phase 2	104 participants (Actual)	Interventional	2018-03-22	Completed
PARP Inhibitor in Combination With CDK4/6 Inhibitor and Endocrine Therapy as the First-line Therapy for HR+/ HER2-Advanced Breast Cancer[NCT05759546]	Phase 2	200 participants (Anticipated)	Interventional	2023-02-01	Recruiting
A Phase 1b / 2a, Open-label Platform Study to Evaluate Mirdametinib as Monotherapy or in Combination With Other Anticancer Agents in Patients With Advanced Solid Cancers Harboring MAPK-activating Mutations[NCT05054374]	Phase 1/Phase 2	6 participants (Actual)	Interventional	2021-09-14	Completed
Precision Platform Study of HR+/ HER2-advanced Breast Cancer Based on SNF Typing (A Prospective, Open-label, Multi-center, Phase II Platform Study)[NCT05594095]	Phase 2	140 participants (Anticipated)	Interventional	2022-12-30	Recruiting
A Randomized Phase II Study of AFP464 +/- Faslodex in ER Positive Breast Cancer Patients Who Had Progressed on Aromatase Inhibitor (AI) Therapy[NCT01233947]	Phase 2	7 participants (Actual)	Interventional	2011-05-31	Terminated
A Phase II Randomized Trial Comparing Alpelisib and Fulvestrant Versus Chemotherapy as Maintenance Therapy in Patients With PIK3CA Mutated Advanced Breast Cancer[NCT03386162]	Phase 2	31 participants (Actual)	Interventional	2018-03-15	Terminated(stopped due to Study was halted Prematurely for low recruitment.)
A Phase II Randomized Trial of Lenvatinib Combined With Letrozole Versus Fulvestrant in Metastatic Estrogen Receptor (ER) Positive, HER2 Negative Breast Cancer, Who Have Progressed on First-line Aromatase Inhibitor + a CDK4/6 Inhibitor.[NCT05181033]	Phase 2	120 participants (Anticipated)	Interventional	2021-12-27	Recruiting
A Phase II Trial Assessing the Tolerability of Palbociclib in Combination With Letrozole or Fulvestrant in Patients Aged 70 and Older With Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer[NCT03633331]	Phase 2	93 participants (Actual)	Interventional	2018-08-15	Active, not recruiting
A Randomized,Double-blind,Parallel-group,Multicentre,Phase II Study to Evaluate the Safety and Pharmacological Activity of the Combination of Vandetanib (100 or 300 MG/Daily or Placebo)With Fulvestrant (Loading Dose)in Postmenopausal Advanced BC Patients[NCT00752986]	Phase 2	39 participants (Actual)	Interventional	2008-12-31	Terminated
Hydroxychloroquine (HCQ) in Combination With Abemaciclib and Endocrine Therapy in HR+/Her 2- Advanced Breast Cancer After a Lead in Dose Escalation Cohort of HCQ and Abemaciclib in Advanced Solid Tumors[NCT04316169]	Phase 1	0 participants (Actual)	Interventional	2021-10-21	Withdrawn(stopped due to Funding and PI leaving institution)
A Randomized, Open Label, Multi-Centre Study to Compare the Efficacy and Tolerability of Fulvestrant 500mg With Exemestane for Postmenopausal Advanced Breast Cancer Patients[NCT02646735]	Phase 2	148 participants (Anticipated)	Interventional	2015-12-31	Recruiting
ALPelisib INdia Safety STudy (ALPINIST): A Phase IV, Prospective, Multicenter, Open-label, Non-comparative, Interventional Study to Assess the Safety of Alpelisib Plus Fulvestrant, in Men and Post-menopausal Women With HR Positive, HER2-negative, Advanced[NCT05631795]	Phase 4	100 participants (Anticipated)	Interventional	2022-08-09	Recruiting
A Phase I/II Multicenter Study of the Combination of AZD2014 and Palbociclib on a Background of Hormonal Therapy in Patients With Locally Advanced/Metastatic Estrogen Receptor Positive Breast Cancer Comprising a Safety, Pharmacokinetic and Preliminary Eff[NCT02599714]	Phase 1	54 participants (Actual)	Interventional	2015-12-07	Completed
MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE 3 TRIAL OF FULVESTRANT (FASLODEX (REGISTERED)). WITH OR WITHOUT PD-0332991 (PALBOCICLIB) +/- GOSERELIN IN WOMEN WITH HORMONE RECEPTOR-POSITIVE, HER2-NEGATIVE METASTATIC BREAST CANCER WHOSE D[NCT01942135]	Phase 3	521 participants (Actual)	Interventional	2013-09-26	Completed
A Phase II, Multi-Centre, Randomized, Double-blind Trial to Evaluate the Therapeutic Benefit of Fulvestrant in Combination With ZACTIMA or Fulvestrant Plus Placebo in Postmenopausal Women With Bone Only or Bone Predominant, Hormone Receptor Positive Metas[NCT00811369]	Phase 2	126 participants (Actual)	Interventional	2009-08-31	Completed
This is a Multicenter, Single Arm, Open-label, run-in Phase Ib / Roll-over Phase II Study of Tucatinib in Combination With Alpelisib in Subjects With PIK3CA-mutant HER2-positive Locally Advanced Unresectable or Metastatic Breast Cancer.[NCT05230810]	Phase 1/Phase 2	40 participants (Anticipated)	Interventional	2022-08-25	Recruiting
Phase II Trial of Palbociclib With Fulvestrant in Individuals With Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer Who Have Progressed on Treatment With Palbociclib and an Aromatase Inhibitor[NCT02738866]	Phase 2	60 participants (Actual)	Interventional	2016-10-25	Active, not recruiting
postMONARCH: A Randomized, Double Blind, Placebo-Controlled, Phase 3 Study to Compare the Efficacy of Abemaciclib Plus Fulvestrant to Placebo Plus Fulvestrant in Participants With HR+, HER2-, Advanced or Metastatic Breast Cancer Following Progression on a[NCT05169567]	Phase 3	350 participants (Anticipated)	Interventional	2022-03-11	Active, not recruiting
EPIK-B4: A Phase II, Multicenter, Randomized, Open-label, Active-controlled Study to Assess the Safety and Efficacy of Dapagliflozin + Metformin XR Versus Metformin XR During Treatment With Alpelisib (BYL719) in Combination With Fulvestrant in Participant[NCT04899349]	Phase 2	2 participants (Actual)	Interventional	2022-04-06	Terminated(stopped due to Study was early terminated due to slow recruitment and emerging data showing that prophylactic use of metformin may prevent or reduce the incidence of all-grades alpelisib-related hyperglycemia. The decision was not driven by safety concerns)
Palbociclib After CDK and Endocrine Therapy (PACE): A Randomized Phase II Study of Fulvestrant, Palbociclib, and Avelumab for Endocrine Pre-treated ER+/HER2- Metastatic Breast Cancer[NCT03147287]	Phase 2	220 participants (Actual)	Interventional	2017-09-05	Active, not recruiting
Open-label, Multicenter, Pilot-trial Evaluating the Safety and Utility of a Hybrid Decentralized Clinical Trial (DCT) Approach Using a TELEmedicine Platform in Patients With HR-positive/HER2-negative Advanced Breast Cancer With a PIK3CA Mutation Treated W[NCT04862143]	Phase 2	2 participants (Actual)	Interventional	2022-03-08	Terminated(stopped due to Study early terminated due to low enrollment compared to the anticipated figures)
Apatinib in Combination With CDK4/6 Inhibitor and Endocrine Therapy as the First-line Therapy for HR+/ HER2-Advanced Breast Cancer[NCT05759572]	Phase 2	145 participants (Anticipated)	Interventional	2023-02-01	Recruiting
A Phase 2, International, Multicenter, Open-labeled, Randomized Trial of PAlbociclib and Fulvestrant vs. Standard Oral Capecitabine In Patients With Hormone Receptor (HR)+ / HER2- Advanced Breast Cancer and Documented Endocrine Resistance[NCT03322215]	Phase 2	42 participants (Actual)	Interventional	2017-10-24	Active, not recruiting
A Randomized Double-blind, Placebo-controlled Study of Ribociclib in Combination With Fulvestrant for the Treatment of Men and Postmenopausal Women With Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer Who Have Received no or Only One Line[NCT02422615]	Phase 3	726 participants (Actual)	Interventional	2015-06-09	Completed
An Open Label, Randomized, Multicenter Study Comparing the Efficacy and Safety of the Combination of Lasofoxifene and Abemaciclib to the Combination of Fulvestrant and Abemaciclib for the Treatment of Pre- and Postmenopausal Women and Men With Locally Adv[NCT05696626]	Phase 3	400 participants (Anticipated)	Interventional	2023-10-31	Recruiting
Comparison of Adjuvant Monotherapy With Endocrine Therapy or Accelerated Partial Breast Irradiation Following Lumpectomy for Low Risk Breast Cancer Patients Over 65 (CAMERAN)[NCT05472792]	Phase 2	90 participants (Anticipated)	Interventional	2022-05-17	Recruiting
Double-Blind Placebo-Controlled Randomized Phase III Trial of Fulvestrant and Ipatasertib as Treatment for Advanced HER-2 Negative and Estrogen Receptor Positive (ER+) Breast Cancer Following Progression on First Line CDK 4/6 Inhibitor and Aromatase Inhib[NCT04650581]	Phase 3	250 participants (Anticipated)	Interventional	2021-01-27	Recruiting
A Randomised, Double-Blind, Parallel-group, Multicentre, Phase III Study Comparing the Efficacy and Tolerability of Fulvestrant (FASLODEX™) 500 mg With Fulvestrant (FASLODEX™) 250 mg in Postmenopausal Women With Oestrogen Receptor Positive Advanced Breast[NCT00099437]	Phase 3	736 participants (Actual)	Interventional	2005-02-13	Active, not recruiting
A Descriptive Study of PIK3CA Mutations and Outcomes With Alpelisib in Patients With HR-positive and HER2-negative Advanced Breast Cancer (ABC)/ Metastatic Breast Cancer (MBC) in India[NCT05022342]		200 participants (Anticipated)	Observational	2021-10-27	Recruiting
Anti-hormonal Maintenance Treatment With the CDK4/6 Inhibitor Ribociclib After 1st Line Chemotherapy in Hormone Receptor Positive / HER2 Negative Metastatic Breast Cancer: A Phase II Trial[NCT03555877]	Phase 2	56 participants (Actual)	Interventional	2018-03-15	Completed
QUILT-3.048: NANT Urothelial Cancer Vaccine: Combination Immunotherapy in Subjects With Urothelial Cancer Who Have Progressed on or After Chemotherapy and Anti-programmed Cell Death Protein 1 (PD-1)/Programmed Death-ligand 1 (PD-L1) Therapy[NCT03197571]	Phase 1/Phase 2	0 participants (Actual)	Interventional	2017-12-31	Withdrawn(stopped due to Trial not initiated)
A Phase Ib/Ⅱ Study of Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of NTQ1062 Tablets in Combination With Fulvestrant in Patients With Advanced HR Positive /HER-2 Negative Breast Cancer[NCT06172322]	Phase 1	42 participants (Anticipated)	Interventional	2023-12-20	Not yet recruiting
An Open Label Randomized Phase 2 Trial of Amcenestrant (SAR439859), Versus Endocrine Monotherapy as Per Physician's Choice in Patients With Estrogen Receptor-positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer With Prior Exposure to Hormo[NCT04059484]	Phase 2	363 participants (Actual)	Interventional	2019-10-22	Active, not recruiting
A Phase I, Open-Label, Multicentre, Dose-Escalation Study to Investigate the Safety and Pharmacokinetics of AZD8835 in Patients With Advanced Solid Tumours[NCT02260661]	Phase 1	20 participants (Actual)	Interventional	2014-11-30	Completed
Exploring Whether Disease-free Intervals Can Guide Endocrine Combined Targeted Therapy for ER+/HER2+ Advanced Breast Cancer (T-sunflower)[NCT05577923]	Phase 2	126 participants (Anticipated)	Interventional	2022-11-01	Not yet recruiting
A Prospective, Single Center, Phase II Trial of Dalpiciclib, Fulvestrant, Trastuzumab and Pertuzumab in HR Positive, HER2 Positive Metastatic Breast Cancer[NCT05574881]	Phase 1/Phase 2	72 participants (Anticipated)	Interventional	2022-09-01	Active, not recruiting
Study to Evaluate the Effect of Metformin in the Prevention of Hyperglycemia in HR[+]/HER2[-] PIK3CA-mutation Advanced Breast Cancer Patients Treated With Alpelisib Plus Endocrine Therapy. Study Metallica[NCT04300790]	Phase 2	68 participants (Actual)	Interventional	2020-10-23	Active, not recruiting
EPIK-B5: A Phase III, Randomized, Double-blind, Placebo-controlled Study of Alpelisib in Combination With Fulvestrant for Men and Postmenopausal Women With HR-positive, HER2-negative Advanced Breast Cancer With a PIK3CA Mutation, Who Progressed on or Afte[NCT05038735]	Phase 3	234 participants (Anticipated)	Interventional	2021-11-29	Recruiting
International,Multicenter,Randomized,Open-label, Phase II to Evaluate the Efficacy and Safety of Continuation of Palbociclib+2nd Line Endocrine Therapy in HR+/HER2- ABC Patients Who Had Clinical Benefit During 1st Line Palbociclib.[NCT03809988]	Phase 2	198 participants (Actual)	Interventional	2019-04-05	Completed
A TREATMENT PROTOCOL FOR PARTICIPANTS CONTINUING FROM PFIZER-SPONSORED PALBOCICLIB CLINICAL STUDIES[NCT05226871]	Phase 2	35 participants (Anticipated)	Interventional	2022-07-07	Recruiting
A Phase 1 Dose Escalation and Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetic, Pharmacodynamic, and Anti-tumor Activity of PF-07248144 in Participants With Advanced or Metastatic Solid Tumors.[NCT04606446]	Phase 1	186 participants (Anticipated)	Interventional	2020-11-16	Recruiting
A Partially-blind Phase III Randomised Trial of Fulvestrant (Faslodex) With or Without Concomitant Anastrozole (Arimidex) Compared With Exemestane in Postmenopausal Women With ER+ve Locally Advanced/Metastatic Breast Cancer Following Progression on Non-st[NCT00944918]	Phase 3	25 participants (Actual)	Interventional	2008-12-31	Completed
Phase II, Open-Labeled, Single-Armed Combination Treatment With Anastrozole, Fulvestrant and Abemaciclib for Hormone Receptor Positive, HER2(-) Metastatic Breast Cancer[NCT05524584]	Phase 2	20 participants (Anticipated)	Interventional	2022-08-31	Recruiting
A Phase II Trial of Neoadjuvant Arimidex With or Without Faslodex in Postmenopausal Women With Hormone Receptor Positive Breast Cancer[NCT00570323]	Phase 2	72 participants (Actual)	Interventional	2007-12-31	Completed
A Randomised Double Blind Placebo Controlled Phase II Study of Fulvestrant With or Without the Addition of Vandetanib as Treatment for Patients With Metastatic Breast Cancer Resistant to Aromatase Inhibitor Therapy[NCT02530411]	Phase 2	160 participants (Anticipated)	Interventional	2015-04-30	Recruiting
Evaluation of the Effects of Endocrine Therapy and Abemaciclib on Host and Tumor Immune Cell Repertoire/Function in Advanced ER+/HER2- Breast Cancer[NCT04352777]	Phase 2	18 participants (Actual)	Interventional	2020-09-14	Active, not recruiting
A Phase II Study, Comparing a Dose-Titration Regimen of Fulvestrant With the Approved Dosing Regimen in Postmenopausal Patients With Hormone-Responsive Advanced Breast Cancer (ABC) (Fulvestrant Intensity Density Study - Studio FIDeS)[NCT00927511]	Phase 2	104 participants (Anticipated)	Interventional	2008-10-31	Recruiting
Randomized Phase II Trial of Preoperative Fulvestrant With or Without Enzalutamide in ER+/Her2- Breast Cancer[NCT02955394]	Phase 2	61 participants (Actual)	Interventional	2017-09-21	Active, not recruiting
Rogaratinib, Palbociclib and Fulvestrant in Advanced Hormone Receptor Positive, FGFR1/2/3-positive Breast Cancer: Phase I Clinical Trial Plus an Expansion Cohort[NCT04483505]	Phase 1	9 participants (Actual)	Interventional	2020-11-25	Completed
Association of Survival With Maintenance Therapy in Patients With Metastatic Breast Cancer After First-line Chemotherapy[NCT04258163]		760 participants (Actual)	Observational	2019-01-01	Completed
"A Double-Blind Phase III Clinical Trial to Compare the Effects of a Pre-Operatively Administered Single Dose of Faslodex (Long-Acting ICI 182.780) With Placebo on Tumor Recurrence in Pre- and Postmenopausal Women Treated for Operable First Primary Breast[NCT00010153]	Phase 3	0 participants	Interventional	2000-11-30	Terminated(stopped due to low accrual)
A Randomized, Open-label, Multi-center Phase IV Study Evaluating Palbociclib Plus Endocrine Treatment Versus a Chemotherapy-based Treatment Strategy in Patients With Hormone Receptor Positive / HER2 Negative Breast Cancer in a Real World Setting (GBG 93 -[NCT03355157]	Phase 4	150 participants (Anticipated)	Interventional	2018-03-01	Recruiting
Phase II Study to Compare Fulvestrant (F) 500mg Plus Placebo vs F 500mg Plus Palbociclib as First Line Treatment for Postmenopausal Women With Hormone Receptor Positive Advanced Breast Cancer Sensitive to Endocrine Therapy. GEICAM/2014-12[NCT02690480]	Phase 2	189 participants (Actual)	Interventional	2016-02-17	Active, not recruiting
Open-label, Two-treatment, Single Period, Parallel, Single-dose, Randomized, Fasting, Lab-blinded Bioequivalence Study of Fulvestrant 50 mg/mL Versus Faslodex®, 50 mg/mL, in Healthy, Post-menopausal Female Subjects[NCT02795039]	Phase 1	266 participants (Actual)	Interventional	2016-06-30	Completed
Pyrotinib Plus Fulvestrant in Patients HR+/HER2+ Metastatic Breast Cancer : a Prospective, Single-arm, Single-center Study[NCT04033172]	Phase 2	40 participants (Anticipated)	Interventional	2018-11-01	Recruiting
A Phase II Study of Palbociclib Plus Fulvestrant for Pretreated Patients With ER+/HER2- Metastatic Breast Cancer[NCT02536742]	Phase 2	124 participants (Actual)	Interventional	2016-08-30	Active, not recruiting
A Phase III Double-blind Randomised Study Assessing the Efficacy and Safety of Capivasertib + Fulvestrant Versus Placebo + Fulvestrant as Treatment for Locally Advanced (Inoperable) or Metastatic Hormone Receptor Positive, Human Epidermal Growth Factor Re[NCT04305496]	Phase 3	818 participants (Actual)	Interventional	2020-04-16	Active, not recruiting
A Randomized, Open Label, Phase III Trial to Evaluate the Efficacy and Safety of Palbociclib + Anti-HER2 Therapy + Endocrine Therapy vs. Anti-HER2 Therapy + Endocrine Therapy After Induction Treatment for Hormone Receptor Positive (HR+)/HER2-Positive Meta[NCT02947685]	Phase 3	496 participants (Anticipated)	Interventional	2017-06-21	Active, not recruiting
A Phase Ib/II Trial of Lenvatinib Plus Pembrolizumab Plus Fulvestrant in ER-positive/ HER2- Negative Metastatic Breast Cancer[NCT06110793]	Phase 1/Phase 2	43 participants (Anticipated)	Interventional	2024-01-31	Not yet recruiting
Phase 2 Trial of Fulvestrant and Binimetinib in Patients With Hormone Receptor-Positive Metastatic Breast Cancer With a Frameshift or Nonsense Mutation or Genomic Deletion in NF1: A ComboMATCH Treatment Trial[NCT05554354]	Phase 2	95 participants (Anticipated)	Interventional	2024-02-29	Recruiting
A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating The Efficacy And Safety Of Multiple Treatment Combinations In Patients With Metastatic Breast Cancer (Morpheus-panBC)[NCT03424005]	Phase 1/Phase 2	242 participants (Anticipated)	Interventional	2018-04-02	Recruiting
A Modular, Multipart, Multiarm, Open-label, Phase I/II Study to Evaluate the Safety and Tolerability of CT7001 Alone and in Combination With Anti-cancer Treatments in Patients With Advanced Malignancies[NCT03363893]	Phase 1/Phase 2	124 participants (Actual)	Interventional	2017-11-14	Completed
Randomized, Open Label, Multicentric Phase III Trial to Evaluate the Safety and Efficacy of Palbociclib in Combination With HT Driven by ctDNA ESR1 Mutation Monitoring in ER+, HER2-negative Metastatic Breast Cancer Patients[NCT03079011]	Phase 3	1,017 participants (Actual)	Interventional	2017-03-22	Active, not recruiting
Palbociclib, Trastuzumab, Pyrotinib and Fulvestrant Treatment in Patients With Brain Metastasis From ER/PR Positive, HER-2 Positive Breast Cancer: A Multi-center, Prospective Study in China[NCT04334330]	Phase 2	34 participants (Anticipated)	Interventional	2020-12-04	Recruiting
A Phase I Trial to Evaluate the Safety of the Addition of Alisertib to Fulvestrant in Women With Advanced Hormone Receptor Positive (HR+) Breast Cancer[NCT02219789]	Phase 1	10 participants (Actual)	Interventional	2014-12-05	Completed
PRECYCLE: Multicenter, Randomized Phase IV Intergroup Trial to Evaluate the Impact of eHealth-based Patient Reported Outcome (PRO) Assessment on Quality of Life in Patients With Hormone Receptor Positive, HER2 Negative Locally Advanced or Metastatic Breas[NCT03220178]	Phase 4	532 participants (Actual)	Interventional	2017-07-24	Terminated(stopped due to Due to COVID-19 pandemic, study cannot be finished in planned timeframe.)
A Phase II Open-label, 2-Part, Multi-center Study of BYL719 (Alpelisib) in Combination With Fulvestrant for Men and Postmenopausal Women With PIK3CA Mutation Hormone Receptor (HR) Positive, HER2-negative, Advanced Breast Cancer Which Progressed on or Afte[NCT04524000]	Phase 2	24 participants (Actual)	Interventional	2020-11-20	Active, not recruiting
Elacestrant Monotherapy vs. Standard of Care for the Treatment of Patients With ER+/HER2- Advanced Breast Cancer Following CDK4/6 Inhibitor Therapy: A Phase 3 Randomized, Open-label, Active-controlled, Multicenter Trial[NCT03778931]	Phase 3	478 participants (Actual)	Interventional	2019-05-10	Active, not recruiting
A Phase IIIb, Open-label, Local, Multicenter Study of the Molecular Features of Postmenopausal Women With Hormone Receptor-positive (HR+) HER2-negative Advanced Breast Cancer on First-line Treatment With Ribociclib Plus Letrozole and, in Patients With a P[NCT03439046]	Phase 3	287 participants (Actual)	Interventional	2018-02-02	Active, not recruiting
Phase II Trial Evaluating Addition of Fulvestrant to Erlotinib in Patients With Stage IIIB/IV NSCLC Who Are Stable on Erlotinib and Exhibit Positivity for Estrogen or Progesterone Receptor[NCT00592007]	Phase 2	7 participants (Actual)	Interventional	2007-09-30	Terminated(stopped due to Study was terminated due to slow subject accrual)
Randomized Phase II Trial to Evaluate Alisertib Alone or Combined With Fulvestrant for Women With Advanced, Endocrine-Resistant Breast Cancer[NCT02860000]	Phase 2	45 participants (Actual)	Interventional	2017-07-06	Active, not recruiting
Retrospective Brazilian Study of Fulvestrant in Advanced Breast Cancer[NCT00660803]		200 participants (Anticipated)	Observational	2008-05-31	Completed
Phase 2 Randomized, Multicenter Study of IMC-A12 as a Single Agent or in Combination With Antiestrogens in Postmenopausal Women With Hormone Receptor-Positive Advanced or Metastatic Breast Cancer After Progression on Antiestrogen Therapy[NCT00728949]	Phase 2	93 participants (Actual)	Interventional	2008-08-31	Completed
Pyrotinib, Dalpiciclib(SHR6390) and Endocrine Therapy in Subjects With Dual-receptor Positive(ER+/HER2+) Advanced Breast Cancer: a Multi-center Phase Ib/II Study[NCT03772353]	Phase 1/Phase 2	59 participants (Actual)	Interventional	2019-05-12	Active, not recruiting
A Randomized, Double-Blind, Phase II Trial of Fulvestrant Plus Enzastaurin Versus Fulvestrant Plus Placebo in Aromatase Inhibitor-Resistant Metastatic Breast Cancer[NCT00451555]	Phase 2	156 participants (Actual)	Interventional	2007-04-11	Completed
An Open Label, Phase 2 Pharmacokinetic Study of Pre-Surgical Intramuscular and Intraductal Fulvestrant in Women With Invasive Breast Cancer or DCIS Undergoing Mastectomy or Lumpectomy[NCT02540330]	Phase 2	3 participants (Actual)	Interventional	2016-03-31	Terminated(stopped due to Business decision)
A Randomized, Prospective Trial of 2-6 Weeks Pre-operative Hormonal Treatment for Hormone Receptor Positive Breast Cancer: Anastrozole +/- Fulvestrant or Tamoxifen Exposure - Response in Molecular Profile (AFTER-study).[NCT00738777]	Phase 2	250 participants (Anticipated)	Interventional	2008-07-31	Suspended(stopped due to in preparation for an amendment)
A Randomised Double-blind Phase IIa Study (With Combination Safety Run-in) to Assess the Safety and Efficacy of AZD4547 in Combination With Fulvestrant vs. Fulvestrant Alone in ER+ Breast Cancer Patients With FGFR1 Polysomy or Gene Amplification Who Have [NCT01202591]	Phase 1/Phase 2	127 participants (Actual)	Interventional	2010-12-31	Completed
A Phase II Study of Combined Fulvestrant (Faslodex) and Everolimus in Advanced/Metastatic Breast Cancer After Aromatase Inhibitor Failure[NCT00570921]	Phase 2	33 participants (Actual)	Interventional	2008-04-30	Completed
Efficacy and Safety of Mecapegfilgrastim for Prophylaxis of Dalpiciclib -Induced Neutropenia in Patients With Advanced HR+/HER2- Breast Cancer: a Open-label, Multicenter, Investigator-initiated, Randomized Controlled Phase II Trial[NCT05463601]	Phase 2	132 participants (Anticipated)	Interventional	2022-08-01	Recruiting
A Single-Arm, Phase 4 Study of Abemaciclib, a CDK4 and CDK6 Inhibitor, in Combination With Endocrine Therapy (Anastrozole/Letrozole or Fulvestrant) in Participants With Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative Locally A[NCT04707196]	Phase 4	200 participants (Actual)	Interventional	2021-02-22	Completed
A Randomized Phase II Study of Fulvestrant vs. Fulvestrant in Combination With Bortezomib in Women With ER Positive Metastatic Breast Cancer[NCT01142401]	Phase 2	118 participants (Actual)	Interventional	2010-05-26	Completed
Role of Endogenous Estrogen in Growth-Hormone Regulation in Postmenopausal Women[NCT01186796]	Phase 1	30 participants (Actual)	Interventional	2009-06-30	Completed
Randomised Phase II Study of Induction Fulvestrant and CDK4/6 Inhibition With the Addition of Ipatasertib in Metastatic ER+/HER2- Breast Cancer Patients Without ctDNA Suppression[NCT04920708]	Phase 2	324 participants (Anticipated)	Interventional	2022-12-28	Recruiting
Phase II Study of ROS1 Targeting With Crizotinib in Advanced E-cadherin Negative, ER Positive Lobular Breast Cancer, Diffuse Gastric Cancer, Triple Negative Lobular Breast Cancer or CDH1-mutated Solid Tumours[NCT03620643]	Phase 2	58 participants (Anticipated)	Interventional	2019-05-09	Active, not recruiting
Phase II Study of Pyrotinib in Combination With Fulvestrant in Patients With Human Epidermal Growth Factor Receptor 2 (HER2) Positive，Hormone Receptor（HR）-Positive Metastatic Breast Cancer[NCT04034589]	Phase 2	46 participants (Anticipated)	Interventional	2019-07-17	Recruiting
Response to Neoadjuvant Treatment With Anti-aromatase Anastrozole and Anti-estrogen Fulvestrant: a Randomized Phase II Study in Postmenopausal Patients With Hormone-sensitive Non-metastatic Breast Cancer and an Exploratory Study of Molecular Signatures of[NCT00871858]	Phase 2	120 participants (Actual)	Interventional	2008-03-18	Completed
A Phase II Clinical Trial Assessing the Safety of an Alternative Dosing Schedule of Palbociclib in Metastatic Hormone Receptor Positive Breast Cancer[NCT03007979]	Phase 2	55 participants (Actual)	Interventional	2017-06-15	Completed
A Phase I-II, Randomization, Open-Label Clinical Trial of Fulvestrant Versus the Combination of Fulvestrant, MK-0646, and Dasatinib as First-Line Therapy for Metastatic Hormone Receptor-Positive HER2-Negative Breast Cancer[NCT00903006]	Phase 1/Phase 2	11 participants (Actual)	Interventional	2009-11-30	Terminated(stopped due to Low Accrual)
Milademetan and Fulvestrant in GATA3-mutant, ER-positive, HER2-negative Advanced or Metastatic Breast Cancer Patients: a Multicenter Phase II Trial[NCT05932667]	Phase 2	1 participants (Actual)	Interventional	2023-10-12	Terminated(stopped due to Financial partner providing study drug could no longer support the trial)
A Phase I Trial of Palbociclib and Bosutinib With Fulvestrant in Patients With Metastatic Hormone Receptor Positive and HER2 Negative (HR+ HER2-) Breast Cancer Refractory to an Aromatase Inhibitor and a CDK4/6 Inhibitor (ASPIRE - WI231696)[NCT03854903]	Phase 1	19 participants (Actual)	Interventional	2019-04-01	Active, not recruiting
Multicenter, Randomized, Open Label Study Evaluating an Anti Insulin-like Growth Factor-1 Receptor (IGF-1R/CD221) Monoclonal Antibody, AVE1642, Administered Every 4 Weeks in Combination With Fulvestrant (Faslodex®) in Postmenopausal Patients With Advanced[NCT00774878]	Phase 2	18 participants (Actual)	Interventional	2008-10-31	Terminated(stopped due to Company decision to discontinue the AVE1642 development program, not due to any safety or efficacy concerns)
An Umbrella, Randomized, Controlled, Pre-Operative Trial Testing Integrative Subtype-Targeted Therapeutics in Hormone Receptor-Positive, HER2-Negative Breast Cancer[NCT05101564]	Phase 2	150 participants (Anticipated)	Interventional	2023-03-20	Recruiting
A Post-trial Access Roll-over Study to Allow Access to Ribociclib (LEE011) for Patients Who Are on Ribociclib Treatment in Novartis-sponsored Study[NCT05161195]	Phase 4	137 participants (Anticipated)	Interventional	2022-07-07	Recruiting
Phase II Randomized Trial of Fulvestrant With or Without Dasatinib in Men and Postmenopausal Women Who Have Hormone Receptor-positive Advanced Breast Cancer Previously Treated With an Aromatase Inhibitor[NCT00754325]	Phase 2	100 participants (Actual)	Interventional	2008-09-30	Completed
Open-label, Randomized, Multicenter, Phase III Study, Comparing Standard Chemotherapy to Standard Combination of Endocrine Therapy With Abemaciclib as Initial Metastatic Treatment Among Patients With Visceral Metastasis of ER+ HER2-breast Cancer, High Bur[NCT04158362]	Phase 3	378 participants (Anticipated)	Interventional	2020-06-11	Recruiting
Phase 2,Open-label,Multicenter,Randomized Study of PD0332991 (Oral CDK4/6 Inhibitor) Monotherapy and in Combination With the HT to Which the pt Has Progressed in the Previous Line for ER+,Her2- Post-menopausal Advanced Breast Cancer Pts[NCT02549430]	Phase 2	115 participants (Actual)	Interventional	2012-10-31	Completed
Comparison of Clinical Efficacy Between Letrozole + Ribociclib and Fulvestrant + Letrozole + Ribociclib in Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer - a Randomized, Phase 2 Study[NCT05816655]	Phase 2	202 participants (Anticipated)	Interventional	2023-05-31	Recruiting
Phase II Clinical Study of Combination of Chidamide and Fulvestrant for HR+/HER2- Breast Cancer That Has Failed Prior Adjuvant Therapy With CDK4/6 Inhibitors[NCT05806047]	Phase 2	23 participants (Anticipated)	Interventional	2023-05-01	Not yet recruiting
Phase II Trial Of Fulvestrant (Faslodex) In Women With Metastatic Breast Cancer And Failure on Aromatase Inhibitor Therapy[NCT00012025]	Phase 2	80 participants (Actual)	Interventional	2001-05-31	Completed
A Two-arm Randomized Open Label Phase 2 Study Of Cp-751,871 In Combination With Exemestane Versus Exemestane Alone As First Line Treatment For Postmenopausal Patients With Hormone Receptor Positive Advanced Breast Cancer[NCT00372996]	Phase 2	219 participants (Actual)	Interventional	2007-02-28	Terminated(stopped due to This study was closed to enrollment as of 13 May 2011 due to business reasons. Premature closure was not prompted by any safety or efficacy concerns.)
AN INTERVENTIONAL, OPEN-LABEL, RANDOMIZED, MULTICENTER PHASE 3 STUDY OF PF-07220060 PLUS FULVESTRANT COMPARED TO INVESTIGATOR'S CHOICE OF THERAPY IN PARTICIPANTS OVER 18 YEARS OF AGE WITH HORMONE RECEPTOR-POSITIVE, HER2-NEGATIVE ADVANCED/METASTATIC BREAST[NCT06105632]	Phase 3	510 participants (Anticipated)	Interventional	2023-12-15	Not yet recruiting
A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Hormone Receptor-Positive HER2-Negative Breast Cancer (MORPHEUS-HR+ Breast Cancer)[NCT03280563]	Phase 1/Phase 2	138 participants (Actual)	Interventional	2017-12-26	Active, not recruiting
A Randomised Phase II Study Comparing Anastrozole and Fulvestrant to Anastrozole for Adjuvant Treatment of Postmenopausal Patients With Early Breast Cancer and Disseminated Tumour Cells in Bone Marrow[NCT00357110]	Phase 2	13 participants (Actual)	Interventional	2006-04-30	Completed
Phase II Study to Evaluate the Efficacy and Tolerability of Fulvestrant 250mg, 250mg Plus 250mg Loading Regimen and 500mg in Postmenopausal Women With ER +ve Advanced Breast Cancer Progressing or Relapsing After Previous Endocrine Therapy[NCT00313170]	Phase 2	144 participants (Actual)	Interventional	2006-05-30	Completed
Phase II Study to Evaluate the Efficacy and Tolerability of Fulvestrant 250mg, 250mg (Plus 250mg Loading Regimen) and 500mg in Postmenopausal Women With ER +ve Advanced Breast Cancer Progressing or Relapsing After Previous Endocrine Therapy[NCT00305448]	Phase 2	143 participants (Actual)	Interventional	2006-03-31	Completed
A Phase II, Double-Blind, Placebo Controlled, Randomized Study to Assess the Efficacy and Safety of AZD2171 in Combination With Fulvestrant vs Fulvestrant Alone in Hormone Sensitive (ER+ve or PgR+ve) Post Menopausal Metastatic Breast Cancer Patients[NCT00454805]	Phase 2	75 participants (Actual)	Interventional	2007-03-31	Completed
An Open, Multicenter Phase II Trial Evaluating the Antitumour Efficacy of Faslodex® (Fulvestrant) in Postmenopausal Women With Advanced Breast Cancer Failing Non-Steroidal or Steroidal Aromatase Inhibitors[NCT00272740]	Phase 2	93 participants	Interventional	2000-03-31	Completed
SEQUence of Endocrine Therapy in Advanced Luminal Breast Cancer (SEQUEL-Breast): A Phase 2 Study on Fulvestrant Beyond Progression in Combination With Alpelisib for PIK3CA-mutated, Hormone-receptor Positive HER2 Negative Advanced Breast Cancer[NCT05392608]	Phase 2	130 participants (Anticipated)	Interventional	2022-06-02	Recruiting
A Phase 1b Multicentre, Open-label, Modular, Dose-finding and Dose-expansion Study to Explore the Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of Trastuzumab Deruxtecan (T-DXd) in Combination With Other Anti-cancer Agents in Patients Wi[NCT04556773]	Phase 1	139 participants (Actual)	Interventional	2020-12-17	Active, not recruiting
A Phase Ib/III Study of Ipatasertib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Hormone Receptor Positive and HER2 Negative Locally Advanced Unresectable or Metastatic Breast Cancer[NCT04060862]	Phase 3	20 participants (Actual)	Interventional	2019-11-15	Completed
Harnessing Olaparib, Palbociclib and Endocrine Therapy: A Phase I/II Trial of Olaparib, Palbociclib and Fulvestrant in Patients With BRCA Mutation-associated, Hormone Receptor-positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Metastatic B[NCT03685331]	Phase 1	54 participants (Anticipated)	Interventional	2020-10-15	Active, not recruiting
Arimidex/Faslodex/Iressa Study: A Phase II Trial of Primary Systemic Therapy Using a Combination of Arimidex, Faslodex and Iressa (Gefitinib) in Postmenopausal Women With Hormone Receptor Positive Breast Cancer[NCT00206414]	Phase 2	15 participants (Actual)	Interventional	2003-01-31	Terminated(stopped due to Difficulty accruing subjects the study accrual was closed)
Phase II Study of Fulvestrant (Faslodex®) in Androgen Independent Prostate Cancer[NCT00244998]	Phase 2	20 participants (Actual)	Interventional	2005-09-30	Completed
A Double-blind, Randomized, Multicentre Trial Comparing the Efficacy and Tolerability of 250mg of Faslodex (Long Acting ICI 182,780) With 20mg of Nolvadex (Tamoxifen) in Postmenopausal Women With Advanced Breast Cancer[NCT00241449]	Phase 3	51 participants (Actual)	Interventional	1998-11-30	Completed
A Phase 1/2, First-in-Human Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, MTD/RP2D, and Antitumor Activity of ARTS-021 as a Single Agent and in Combination Therapy in Patients With Solid Tumors[NCT05867251]	Phase 1/Phase 2	192 participants (Anticipated)	Interventional	2023-08-30	Recruiting
A Phase 1/2 Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of BLU-222 as a Single Agent and in Combination Therapy for Patients With Advanced Solid Tumors[NCT05252416]	Phase 1/Phase 2	366 participants (Anticipated)	Interventional	2022-04-07	Recruiting
A Phase 1-2 Dose-Escalation and Cohort-Expansion Study of Intravenous Zotatifin (eFT226) in Subjects With Selected Advanced Solid Tumor Malignancies[NCT04092673]	Phase 1/Phase 2	30 participants (Anticipated)	Interventional	2019-10-25	Recruiting
Randomized Phase II Study Comparing Two Different Schedules of Palbociclib Plus Second Line Endocrine Therapy in Women With Estrogen Receptor Positive, HER2 Negative Advanced/Metastatic Breast Cancer[NCT02630693]	Phase 2	180 participants (Actual)	Interventional	2016-04-08	Completed
A Partially-Blind Phase III Randomized Trial of Fulvestrant (Faslodex™) With or Without Concomitant Anastrozole (Arimidex™) Compared With Exemestane in Postmenopausal Women With ER+ve Locally Advanced/Metastatic Breast Cancer Following Progression on Non-[NCT00253422]	Phase 3	750 participants (Anticipated)	Interventional	2004-03-31	Active, not recruiting
Maintenance Hormone Therapy With Fulvestrant After First-Line Chemotherapy for Postmenopausal Hormone-receptor-positive (HR) Positive Advanced Breast Cancer: A Multicenter, Prospective Phase II Study[NCT02000193]	Phase 2	58 participants (Actual)	Interventional	2013-11-30	Active, not recruiting
Phase 3, Open-Label, Randomized, Study Comparing Gedatolisib Combined With Fulvestrant & With or Without Palbociclib to Standard-of-Care Therapies in Patients With HR-Positive, HER2-Negative Advanced Breast Cancer Previously Treated With a CDK4/6 Inhibito[NCT05501886]	Phase 3	701 participants (Anticipated)	Interventional	2022-09-30	Recruiting
An Open-Label Phase II Trial of Fulvestrant And Neratinib in Previously Treated HRPositive, HER2-Negative Metastatic Breast Cancer Subjects Assessed With a Test Measuring Live Cell HER2 Signaling Function[NCT04901299]	Phase 2	0 participants (Actual)	Interventional	2023-07-31	Withdrawn(stopped due to Team decision)
A Randomized Phase II Trial Of Circulating Tumor DNA-Guided Second Line Adjuvant Therapy For High Residual Risk, Stage II-III, Hormone Receptor Positive, HER2 Negative Breast Cancer[NCT04567420]	Phase 2	100 participants (Anticipated)	Interventional	2021-02-09	Recruiting
A Phase 2 Study of Neratinib With or Without Fulvestrant in HER2-Positive, ER-Positive Metastatic Breast Cancer[NCT03289039]	Phase 2	21 participants (Actual)	Interventional	2017-10-25	Terminated(stopped due to Slow accrual)
Impact of Endogenous Estrogen on Somatostatin Inhibition and Growth Hormone Rebound in Older Women[NCT02026973]	Phase 1	62 participants (Actual)	Interventional	2014-03-31	Completed
Phase III Study of Palbociclib in Combination With Exemestane or Fulvestrant vs. Chemotherapy (Capecitabine) in Hormonal Receptor Positive/HER2 Negative Metastatic Breast Cancer Patients With Resistance to Aromatase Inhibitors[NCT02028507]	Phase 3	693 participants (Actual)	Interventional	2014-03-13	Completed
A Phase II Trial to Evaluate Functional Imaging in Prediction of Response to Abemaciclib for Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer[NCT06179303]	Phase 2	60 participants (Anticipated)	Interventional	2024-06-01	Not yet recruiting
A Randomized, Double-blind, Parallel-controlled Phase III Trial Evaluating the Efficacy and Safety of TQB3616 in Combination With Fulvestrant Versus Placebo in Combination With Fulvestrant in Previously Untreated HR-positive, HER2-negative Advanced Breast[NCT05365178]	Phase 3	432 participants (Actual)	Interventional	2022-07-01	Active, not recruiting
A PHASE 1/2A STUDY EVALUATING THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTI-TUMOR ACTIVITY OF PF-07220060 AS A SINGLE AGENT AND AS PART OF COMBINATION THERAPY IN PARTICIPANTS WITH ADVANCED SOLID TUMORS[NCT04557449]	Phase 1/Phase 2	337 participants (Anticipated)	Interventional	2020-09-23	Recruiting
A Randomized Phase II Study of Fulvestrant in Combination With the Dual mTOR Inhibitor AZD2014 or Everolimus or Fulvestrant Alone in Estrogen Receptor-positive Advanced or Metastatic Breast Cancer[NCT02216786]	Phase 2	333 participants (Actual)	Interventional	2014-01-31	Active, not recruiting
A Phase I, Open, Multicenter Study of BEBT-209 in Women With Advanced Breast Cancer[NCT06047184]	Phase 1	106 participants (Anticipated)	Interventional	2019-07-15	Active, not recruiting
A PHASE 3, RANDOMIZED, OPEN-LABEL, MULTICENTER TRIAL OF ARV-471 (PF-07850327) VS FULVESTRANT IN PARTICIPANTS WITH ESTROGEN RECEPTOR-POSITIVE, HER2-NEGATIVE ADVANCED BREAST CANCER WHOSE DISEASE PROGRESSED AFTER PRIOR ENDOCRINE BASED TREATMENT FOR ADVANCED [NCT05654623]	Phase 3	560 participants (Anticipated)	Interventional	2023-03-03	Recruiting
Targeting Insulin Feedback to Enhance Alpelisib (TIFA): A Phase 2 Randomized Control Trial in Metastatic PIK3CA-mutant Hormone-Receptor Positive Breast Cancer[NCT05090358]	Phase 2	106 participants (Anticipated)	Interventional	2021-10-08	Recruiting
Alpelisib (Piqray®) Post-Authorization Safety Study (PASS): a Non-interventional Study of Alpelisib in Combination With Fulvestrant in Postmenopausal Women, and Men, With Hormone Receptor Positive (HR+), Human Epidermal Growth Factor Receptor 2 Negative ([NCT04967248]		150 participants (Anticipated)	Observational	2023-06-21	Recruiting
A Phase 1b Study of Abemaciclib in Combination With Therapies for Patients With Metastatic Breast Cancer[NCT02057133]	Phase 1	198 participants (Anticipated)	Interventional	2014-03-10	Active, not recruiting
A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Compare NSAI (Anastrozole or Letrozole) Plus Abemaciclib, a CDK4 and CDK6 Inhibitor, or Plus Placebo, and to Compare Fulvestrant Plus Abemaciclib or Plus Placebo in Postmenopausal Women With[NCT02763566]	Phase 3	463 participants (Actual)	Interventional	2016-12-05	Active, not recruiting
monarcHER: A Phase 2, Randomized, Multicenter, 3-Arm, Open-Label Study to Compare the Efficacy of Abemaciclib Plus Trastuzumab With or Without Fulvestrant to Standard-of-Care Chemotherapy of Physician's Choice Plus Trastuzumab in Women With HR+, HER2+ Loc[NCT02675231]	Phase 2	237 participants (Actual)	Interventional	2016-05-23	Active, not recruiting
Real-world Effectiveness and Safety of a Generic Fulvestrant Alone or in Combination With Cyclin Inhibitors in Postmenopausal Women With Advanced Breast Cancer HR+, HER2-, in Two Colombian Referral Centers[NCT05140655]		40 participants (Anticipated)	Observational	2021-04-19	Recruiting
Phase II Trial to Evaluate the Efficacy of the FASN Inhibitor, TVB-2640, in Combination With Trastuzumab Plus Paclitaxel or Endocrine Therapy in Patients With HER2+ Metastatic Breast Cancer Resistant to Trastuzumab-Based Therapy[NCT03179904]	Phase 2	80 participants (Anticipated)	Interventional	2017-08-03	Recruiting
Overcoming Endocrine Resistance in Metastatic Breast Cancer: A Randomized Trial With Factorial Design Comparing Fulvestrant ± Lapatinib ± Aromatase Inhibitor in Metastatic Breast Cancer Progressing After Aromatase Inhibitor Therapy[NCT00688194]	Phase 3	396 participants (Anticipated)	Interventional	2008-05-31	Recruiting
An Open-label Phase 1b Study of E7090 Monotherapy and in Combination With Other Anticancer Agents in Subjects With ER+, HER2- Recurrent/Metastatic Breast Cancer[NCT04572295]	Phase 1	72 participants (Anticipated)	Interventional	2020-10-09	Active, not recruiting
Phase I Trial of Vandetanib (ZD6474, Zactima) and Fulvestrant (Faslodex) as Third-Line Treatment of Advanced Non-Small Cell Lung Cancer[NCT01004419]	Phase 1	0 participants (Actual)	Interventional	2009-11-30	Withdrawn(stopped due to Support for investigational products has been withdrawn.)
An Open-label, Interventional, Multicenter, Randomized, Phase 2 Study of Fulvestrant With or Without Samuraciclib in Participants With Metastatic or Locally Advanced Hormone Receptor (HR) Positive and Human Epidermal Growth Factor Receptor (HER)2-Negative[NCT05963984]	Phase 2	60 participants (Anticipated)	Interventional	2023-12-14	Recruiting
A Phase III, Randomized, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With The Physician's Choice of Endocrine Therapy Plus Everolimus in Patients With Estrogen Receptor-Positive, HER2-Negative,[NCT05306340]	Phase 3	320 participants (Anticipated)	Interventional	2022-08-03	Recruiting
A Double-Blind, Randomized, Multi-Center Trial Comparing the Efficacy and Tolerability of 125 and 250mg of Faslodex (Long Acting ICI 182,780) With 1mg Arimidex (Anastrazole) in Postmenopausal Women With Advanced Breast Cancer.[NCT00635713]	Phase 3	588 participants (Anticipated)	Interventional	1997-05-31	Completed
An Open, Multicenter Study for the Predicted Biomarkers of CDK4/6 Inhibitors (Palbociclib) in ER-positive Metastasis Breast Cancer[NCT04289974]		100 participants (Anticipated)	Observational	2019-02-14	Recruiting
A Randomized Multicenter Phase II Study Identifying Hormone Sensitivity Profiles and Evaluating the Efficacy of Anastrozole and Fulvestrant in the Neo-adjuvant Treatment of Operable Breast Cancer in Postmenopausal Women.[NCT00629616]	Phase 2	116 participants (Actual)	Interventional	2007-10-31	Completed
An Open-label, Non-Comparative Trial to Evaluate the Safety, Efficacy and Pharmacokinetics of Faslodex (Fulvestrant) in Girls With Progressive Precocious Puberty Associated With McCune-Albright Syndrome[NCT00278915]	Phase 2	30 participants (Actual)	Interventional	2006-01-31	Active, not recruiting
A Retrospective Study of Fulvestrant in Postmenopausal Patients With Metastatic Breast Cancer in Greece (The 'RESPONSE' Study)[NCT01399086]		140 participants (Actual)	Observational	2011-04-30	Completed
A Multicenter, Prospective, Real-world Study to Evaluate the Safety Profile and Effectiveness in Chinese Patients Who Received Fulvestrant 500mg as First-line Endocrine Treatment for Advanced Breast Cancer[NCT02909361]		500 participants (Anticipated)	Observational [Patient Registry]	2017-10-11	Active, not recruiting
A PHASE 1B/2, OPEN-LABEL, MULTICENTER, DOSE ESCALATION AND DOSE EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTITUMOR ACTIVITY OF PF-07220060 IN COMBINATION WITH PF-07104091 PLUS ENDOCRINE THERAPY IN PARTI[NCT05262400]	Phase 1/Phase 2	240 participants (Anticipated)	Interventional	2022-03-14	Recruiting
Phase 2 Study of PI3K Inhibitor Copanlisib in Combination With Fulvestrant in Selected ER+ and/or PR+ Cancers With PI3K (PIK3CA, PIK3R1) and/or PTEN Alterations[NCT05082025]	Phase 2	7 participants (Actual)	Interventional	2022-09-27	Active, not recruiting
BYLieve: A Phase II, Multicenter, Open-label, Three-cohort, Non- Comparative Study to Assess the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole in Patients With PIK3CA Mutant, Hormone Receptor (HR) Positive, HER2-negative Advanced Breast C[NCT03056755]	Phase 2	383 participants (Actual)	Interventional	2017-08-14	Active, not recruiting
Phase II Trial of Fulvestrant Plus Enzalutamide in ER+/Her2- Advanced Breast Cancer[NCT02953860]	Phase 2	32 participants (Actual)	Interventional	2017-07-06	Completed
Neoadjuvant Hormonal Therapy Combined With Chemoimmunotherapy (Taxotere, Trastuzumab and Pertuzumab) in Patients With HER2-positive and ER-Positive Breast Cancer (NeoHTTP Study)[NCT02345772]	Phase 1/Phase 2	4 participants (Actual)	Interventional	2014-07-31	Terminated(stopped due to PI no longer at site. Data was not collected)
Randomized, Double Blind Multicenter Phase II Study of Time to Progression on Fulvestrant in Combination With Erlotinib or Placebo in Hormone Receptor-Positive Metastatic Breast Cancer (MBC) Subjects Who Progressed on First Line Hormonal Therapy[NCT00570258]	Phase 2	27 participants (Actual)	Interventional	2006-09-30	Terminated(stopped due to FDA approved higher dose of study drug. Dose used in protocol lower than SOC - enrollment stopped, those on treatment were given option to opt out.)
A Phase 1 Study of a CDK 4/6 Dual Inhibitor in Participants With Advanced Cancer[NCT01394016]	Phase 1	225 participants (Actual)	Interventional	2009-12-07	Completed
Randomized Phase II Study of Fulvestrant With or Without Ganetespib in Patients With Hormone Receptor-Positive, Metastatic Breast Cancer[NCT01560416]	Phase 2	50 participants (Actual)	Interventional	2012-05-31	Active, not recruiting
A Randomised, Double-Blind, Parallel-Group, Multicentre Study Comparing the Efficacy and Tolerability of Fulvestrant 500 mg Versus 250 mg in Postmenopausal Women With ER+ Advanced Breast Cancer Progressing or Relapsing After Previous Endocrine Therapy[NCT01300351]	Phase 3	249 participants (Actual)	Interventional	2011-03-31	Completed
Clinical Application of Circulating Tumor DNA (ctDNA) to Guided the Late-Line Treatment for Patients With Late-Stage Breast Cancer[NCT05427617]		223 participants (Actual)	Observational	2016-12-01	Completed
Fulvestrant or Capecitabine Combined With Pyrotinib in HR-positive and HER2-Positive Metastatic Breast Cancer: A Multicenter, Randomized, Phase III Study[NCT04646759]	Phase 3	516 participants (Anticipated)	Interventional	2020-10-14	Recruiting
A Phase II Multi-Center Study to Evaluate the Efficacy and Safety of 500mg of Fulvestrant (Faslodex) as a First Line Hormonal Treatment in Postmenopausal Women With Hormone Receptor Positive Metastatic Breast Cancer[NCT00585507]	Phase 2	40 participants (Anticipated)	Interventional	2004-04-30	Active, not recruiting
A Phase 1 First-in-Human Dose Study of LY3023414 in Patients With Advanced Cancer[NCT01655225]	Phase 1	156 participants (Actual)	Interventional	2012-07-31	Completed
Clinical Study of Chidamide Combined With Fulvestrant in the Treatment of Hormone Receptor-positive Advanced Breast Cancer[NCT05047848]		82 participants (Anticipated)	Interventional	2021-08-18	Recruiting
A Multicenter, Randomized, Double Blind, Placebo Controlled, Phase II Trial Evaluating the Safety and Efficacy of Dovitinib Combined With Fulvestrant, in Postmenopausal Patients With HER2- and HR+ Breast Cancer That Have Evidence of Disease Progression on[NCT01528345]	Phase 2	97 participants (Actual)	Interventional	2012-04-30	Terminated(stopped due to Slow and low enrollment)
A Phase II Trial to Evaluate the Combination of ZD1839 (Iressa) and Fulvestrant (Faslodex®) in Patients With Advanced or Metastatic Breast Cancer[NCT00234403]	Phase 2	60 participants	Interventional	2004-05-31	Completed
A Randomized, Open-Label Phase II Clinical Trial of Combination Erlotinib (Tarceva®) and Fulvestrant (Faslodex®) Versus Erlotinib (Tarceva®) Alone in Advanced Non-Small Cell Lung Cancer Patients[NCT00100854]	Phase 2	108 participants (Actual)	Interventional	2004-10-28	Completed
Phase II Study of Efficacy of ICI 182,780 (Faslodex) in the Treatment of Systemic Lupus Erythematosus: Clinical, Serologic, Molecular[NCT00417430]	Phase 2	20 participants	Interventional	2004-09-30	Completed
Levels of Circulating Tumor DNA as a Predictive Marker for Early Switch in Treatment for Patients With Metastatic (Stage IV) Breast Cancer: A Phase 2 Randomized, Open-Label Study[NCT05826964]	Phase 2	500 participants (Anticipated)	Interventional	2023-06-12	Recruiting
A Phase 2 Study of TAS-120 in Metastatic Breast Cancers Harboring Fibroblast Growth Factor Receptor (FGFR) Amplifications[NCT04024436]	Phase 2	168 participants (Anticipated)	Interventional	2019-08-30	Active, not recruiting
BOOG 2017-03: Endocrine Therapy Plus CDK 4/6 Inhibition in First- or Second-line for Hormone Receptor Positive Advanced Breast Cancer - the SONIA Study[NCT03425838]	Phase 3	1,050 participants (Actual)	Interventional	2017-11-09	Active, not recruiting
A Double Blind, Double Dummy, Randomised, Multicentre Study to Compare the Efficacy and Safety of Fulvestrant 250mg With Arimidex 1mg as a Secondary-line Therapy in the Postmenopausal Women With Oestrogen Receptor Positive Advanced Breast Cancer[NCT00327769]	Phase 3	234 participants (Actual)	Interventional	2005-11-30	Completed
An Open, Multicentre Phase I Clinical Study to Assess the Tolerability of Fulvestrant 500 mg in Postmenopausal Women With Hormone Receptor Positive Advanced or Recurrent Breast Cancer[NCT00328120]	Phase 1	20 participants (Actual)	Interventional	2004-04-30	Completed
A Randomized, Open-Label, Multicenter, Phase II Study Comparing the Effects on Proliferation and the Efficacy and Tolerability of Fulvestrant (FASLODEX®) 500 mg With Fulvestrant (FASLODEX®) 250 mg When Given as Neoadjuvant Treatment in Postmenopausal Wome[NCT00093002]	Phase 2	179 participants (Actual)	Interventional	2004-06-30	Completed
A Phase II Study of Fulvestrant in Premenopausal Women With Hormone Receptor-Positive Breast Cancer[NCT00146601]	Phase 2	35 participants (Anticipated)	Interventional	2004-06-30	Completed
Molecular Analysis for Combination Therapy Choice (ComboMATCH)[NCT05564377]	Phase 2	2,900 participants (Anticipated)	Interventional	2023-04-07	Recruiting
An Open Label, Phase Ib, Dose-escalation Study Evaluating the Safety and Tolerability of Xentuzumab and Abemaciclib in Patients With Locally Advanced or Metastatic Solid Tumours and in Combination With Endocrine Therapy in Patients With Locally Advanced o[NCT03099174]	Phase 1	133 participants (Actual)	Interventional	2017-05-04	Active, not recruiting
A Phase 1 Study of SY 5609, an Oral, Selective CDK7 Inhibitor, in Adult Patients With Select Advanced Solid Tumors[NCT04247126]	Phase 1	105 participants (Actual)	Interventional	2020-01-23	Completed
Open-label, Multi-center, sINGlE Arm Clinical Study to Evaluate Efficacy/QoL in Women With HR+, HER2-, Regionally Recurrent or Metastatic Breast Cancer Receiving Palbociclib With an AI or Fulvestrant After Prior Endocrine Therapy[NCT02894398]	Phase 2	388 participants (Actual)	Interventional	2016-09-06	Completed
A Phase Ib, Single-arm, Open-label Study of TQ-B3525 Tablets Combined With Fulvestrant Injection in Subjects With HR-positive, HER2-negative and PIK3CA Mutation Advanced Breast Cancer[NCT04355520]	Phase 1/Phase 2	42 participants (Anticipated)	Interventional	2020-07-31	Not yet recruiting
A Phase 3, Randomized, Multicenter, Open-Label Study to Compare the Efficacy and Safety of Anti-HER2 Therapy Plus Fulvestrant or Capecitabine in First-line Treatment of Women With HR+, HER2+, Non-visceral Metastases, Stage IV Breast Cancer[NCT04337658]	Phase 3	493 participants (Anticipated)	Interventional	2020-07-01	Not yet recruiting
A Clinical Trial to Compare Efficacy and Tolerability of Atorvastatin in Addition to Endocrine Treatment With Focus on Mechanisms of Resistance to Endocrine Treatment (Fulvestrant/Aromatase Inhibitors) in Patients With Advanced Breast Cancer[NCT02958852]	Phase 2	126 participants (Anticipated)	Interventional	2016-11-30	Recruiting
A Study of LOXO-783 Administered as Monotherapy and in Combination With Anticancer Therapies for Patients With Advanced Breast Cancer and Other Solid Tumors With a PIK3CA H1047R Mutation[NCT05307705]	Phase 1	400 participants (Anticipated)	Interventional	2022-05-11	Recruiting
A Phase II Trial of OnapriStone in CoMbInation With FuLvestrant for Patients With ER-positive, and HER2-negative Metastatic Breast Cancer After Progression on Endocrine Therapy and CDK 4/6 Inhibitors[NCT04738292]	Phase 2	11 participants (Actual)	Interventional	2021-10-05	Terminated(stopped due to funding)
Treatment of Metastatic Breast Cancer With Fulvestrant Plus Palbociclib or Tamoxifen Plus Palbociclib: A Randomized Pilot Trial With ESR1 Mutation Tested in Circulating Tumor DNA.[NCT02913430]	Early Phase 1	7 participants (Actual)	Interventional	2018-04-24	Active, not recruiting
Combination of Abemaciclib and Endocrine Therapy in Hormone Receptor Positive HER2 Negative Locally Advanced or Metastatic Breast Cancer With Focus on Digital Side Effect Management. The MINERVA Trial - A Phase IV Trial[NCT05362760]	Phase 4	300 participants (Anticipated)	Interventional	2022-04-27	Recruiting
A Pilot Clinical Trial to Evaluate the Biological Activity of Fulvestrant (Faslodex) in Breast Ductal Carcinoma (DCIS)[NCT00126464]		100 participants (Anticipated)	Interventional	2004-11-30	Active, not recruiting
Randomized, Non-Comparative Phase 1/2 Study of NUV-422 in Combination With Fulvestrant in Patients With Hormone Receptor-Positive Human Epidermal Growth Factor Receptor 2-Negative (HR+HER2-) Advanced Breast Cancer (aBC)[NCT05191004]	Phase 1/Phase 2	0 participants (Actual)	Interventional	2022-09-30	Withdrawn(stopped due to Sponsor decision)
A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Alobresib (Formerly GS-5829) as a Monotherapy in Subjects With Advanced Solid Tumors and Lymphomas and in Combination With Exemestane or Fulvestrant in Subject[NCT02392611]	Phase 1	33 participants (Actual)	Interventional	2015-03-16	Completed
Treatment of Dalpiciclib Combined With Pyrotinib for Trastuzumab-sensitive HER2+ Advanced Breast Cancer: a Single Arm, Dual Cohort, Prospective, Open Phase II Exploratory Study[NCT05328440]	Phase 2	120 participants (Anticipated)	Interventional	2022-05-20	Recruiting
A Phase 2 Study of Copanlisib (BAY 80-6946) in Combination With Fulvestrant in Patients With Metastatic Breast Cancer Progressing After Aromatase Inhibitor Plus CDK 4/6 Inhibitor[NCT03803761]	Phase 1/Phase 2	0 participants (Actual)	Interventional	2019-02-13	Withdrawn(stopped due to Inadequate accrual rate)
Phase II Randomised Clinical Trial Evaluating an EGFR Tyrosine Kinase Inhibitor (EGFR-TKI) Versus an EGFR-TKI Combined With an Anti-oestrogen Treatment (Fulvestrant) in Women With Advanced Stage Non-squamous Lung Cancer[NCT01556191]	Phase 2	379 participants (Actual)	Interventional	2012-05-15	Completed
P3 Efficacy Evaluation of Enobosarm in Combo With Abemaciclib Compared to Estrogen Blocking Agent for 2nd Line Treatment of ER+HER2- MBC in Patients Who Have Shown Previous Disease Progression on an Estrogen Blocking Agent Plus Palbociclib[NCT05065411]	Phase 3	186 participants (Anticipated)	Interventional	2022-04-11	Active, not recruiting
STEM: A Multicentre Phase 2 Study of SFX-01 Treatment and Evaluation in Patients With Estrogen Receptor (ER) Positive and Human Epidermal Growth Factor Receptor 2 (HER2) Negative Metastatic Breast Cancer Progressing on Either an Aromatase Inhibitor (AI) o[NCT02970682]	Phase 2	60 participants (Anticipated)	Interventional	2016-10-31	Completed
An Open-Label, Randomized, Multicenter Study Evaluating the Activity of Lasofoxifene Relative to Fulvestrant for the Treatment of Pre- and Postmenopausal Women With Locally Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation[NCT03781063]	Phase 2	100 participants (Anticipated)	Interventional	2019-09-20	Active, not recruiting
A Multicenter, Randomized, Double-blind, Placebo-controlled Phase III Clinical Study to Evaluate the Efficacy and Safety of FCN-437c Versus Placebo Combined With Fulvestrant ± Goserelin in Women With HR+ and HER2- Advanced Breast Cancer[NCT05438810]	Phase 3	312 participants (Anticipated)	Interventional	2022-01-18	Recruiting
A Randomized, Double Blind, Multicenter Study to Compare the Efficacy and Tolerability of Fulvestrant (FASLODEX™) vs. Exemestane (AROMASIN™) in Postmenopausal Women With Hormone Receptor Positive Advanced Breast Cancer With Disease Progression After Prior[NCT00065325]	Phase 3	694 participants (Actual)	Interventional	2003-08-31	Completed
A Randomized, Multi-center, Open-label, Phase III Trial of Fulvestrant Versus Capecitabine as Maintenance Therapy After First-line Chemotherapy in Patients With Hormone Receptor Positive, Human Epidermal Growth Factor Receptor-2 Negative Metastatic Breast[NCT04263298]	Phase 3	210 participants (Anticipated)	Interventional	2018-05-01	Recruiting
Neoadjuvant With Trastuzumab, Pyrotinib Plus Palbociclib and Fulvestrant in HER2-positive, ER-positive Breast Cancer[NCT05076695]	Phase 2	37 participants (Anticipated)	Interventional	2021-10-15	Recruiting
Fulvestrant in Hormone-refractory Prostate Cancer[NCT00476645]	Phase 2	10 participants (Actual)	Interventional	2006-09-30	Completed
An Open-Label Phase 2 Study of MLN0128 (A TORC1/2 Inhibitor) in Combination With Fulvestrant in Women With ER-Positive/HER2-Negative Advanced or Metastatic Breast Cancer That Has Progressed During or After Aromatase Inhibitor Therapy[NCT02756364]	Phase 2	141 participants (Actual)	Interventional	2016-07-28	Completed
A Double-blind, Randomized, Multicentre Trial to Compare the Anti-tumour Effects and Tolerability of a 500 mg Dose of Faslodex (Fulvestrant) Plus Arimidex (Anastrozole) With a 500 mg Dose of Faslodex(Fulvestrant) Alone and With Arimidex(Anastrozole) Alone[NCT00259090]	Phase 2	120 participants (Actual)	Interventional	2004-04-30	Completed
A Phase 2 Basket Study of Tucatinib in Combination With Trastuzumab in Subjects With Previously Treated, Locally Advanced Unresectable or Metastatic Solid Tumors Driven by HER2 Alterations[NCT04579380]	Phase 2	217 participants (Actual)	Interventional	2021-01-11	Active, not recruiting
A Phase II Randomized Double-blind, Placebo-controlled Study of Alpelisib in Combination With Fulvestrant for Chinese Men and Postmenopausal Women With Hormone Receptor Positive, HER2-negative, PIK3CA Mutant Advanced Breast Cancer Which Progressed on or A[NCT04544189]	Phase 2	135 participants (Anticipated)	Interventional	2021-01-20	Recruiting
A Phase III Randomized Double-blind, Placebo Controlled Study of Alpelisib in Combination With Fulvestrant for Men and Postmenopausal Women With Hormone Receptor Positive, HER2-negative Advanced Breast Cancer Which Progressed on or After Aromatase Inhibit[NCT02437318]	Phase 3	572 participants (Actual)	Interventional	2015-07-23	Completed
A Phase III, Multicenter, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Versus Alpelisib Plus Fulvestrant in Patients With Hormone Receptor-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metas[NCT05646862]	Phase 3	400 participants (Anticipated)	Interventional	2023-06-07	Recruiting
A Open-label, Multicenter Phase II Study of TQB3616 Capsules Combined With Fulvestrant Injection in Subjects With HR-positive, HER2-negative Advanced Breast Cancer[NCT04796623]	Phase 2	120 participants (Anticipated)	Interventional	2021-02-04	Recruiting
A Phase II Study of Ribociclib And Endocrine Treatment of Physician's Choice for Locoregional Recurrent, Resected Hormone Receptor Positive HER2 Negative Breast Cancer[NCT05467891]	Phase 2	200 participants (Anticipated)	Interventional	2022-09-13	Recruiting
Phase II Trial of Fulvestrant Plus Abemaciclib With or Without Run-in of Fulvestrant in Er-Positive, Her2-Negative Metastatic Breast Cancer After Failure of a CDK4/6 Inhibitor In Combination With an Aromatase Inhibitor[NCT05305924]	Phase 2	56 participants (Anticipated)	Interventional	2021-02-25	Recruiting
A Phase 1b Study of Talimogene Laherparepvec (T-VEC) in Combination With Chemotherapy or Endocrine Therapy in Patients With Metastatic, Unresectable, or Locoregionally Recurrent HER2-negative Breast Cancer[NCT03554044]	Phase 1	20 participants (Actual)	Interventional	2020-02-05	Active, not recruiting
Phase II Safety Study of Palbociclib in Combination With Letrozole or Fulvestrant in African American Women With Hormone Receptor Positive HER2 Negative Advanced Breast Cancer[NCT02692755]	Phase 2/Phase 3	35 participants (Actual)	Interventional	2016-09-30	Completed
A First-in-Human Study of PI3Kα Inhibitor, RLY-5836, in Combination With Targeted and Endocrine Therapies in Participants With Advanced Breast Cancer and as a Single Agent in Advanced Solid Tumors[NCT05759949]	Phase 1	265 participants (Anticipated)	Interventional	2023-03-29	Recruiting
Phase Ib/II Study of Chidamide in Combination With Abemaciclib and Fulvestrant in Patients Previously Treated With Palbociclib in HR+/HER2-Relapsed/Metastatic Breast Cancer[NCT05464173]	Phase 1/Phase 2	44 participants (Anticipated)	Interventional	2022-07-01	Recruiting
A Randomised, Double-blind, Parallel-group, Multicentre, Phase III Study to Compare the Efficacy and Tolerability of Fulvestrant (FASLODEX) 500 mg With Anastrozole (ARIMIDEX) 1 mg as Hormonal Treatment for Postmenopausal Women With Hormone Receptor-Positi[NCT01602380]	Phase 3	462 participants (Actual)	Interventional	2012-10-17	Active, not recruiting
A Pilot Clinical Trial to Evaluate the Biological Activity of Fulvestrant in Breast Ductal Carcinoma in Situ (DCIS)[NCT00183963]	Phase 2	4 participants (Actual)	Interventional	2006-08-31	Terminated(stopped due to Insufficient accrual)
A Phase II, Single Arm, Open-label Trial of Dalpiciclib Plus Fulvestrant With Pyrotinib in Hormone Receptor-positive, HER2-low Advanced Breast Cancer That Progressed on Previous CDK4/6i Plus AI Therapy[NCT05806671]	Phase 2	30 participants (Anticipated)	Interventional	2023-05-31	Not yet recruiting
A Phase II, Double-Blind, Placebo Controlled, Randomized Study of GDC-0941 or GDC-0980 With Fulvestrant Versus Fulvestrant in Advanced or Metastatic Breast Cancer in Patients Resistant to Aromatase Inhibitor Therapy[NCT01437566]	Phase 2	318 participants (Actual)	Interventional	2011-10-31	Completed
A PHASE 1, OPEN-LABEL, MULTICENTER, DOSE ESCALATION AND DOSE EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTITUMOR ACTIVITY OF PF-07224826, AS A SINGLE AGENT AND IN COMBINATION WITH ENDOCRINE THERAPY IN PA[NCT05905341]	Phase 1	0 participants (Actual)	Interventional	2024-01-15	Withdrawn(stopped due to This decision was based on business considerations and not due to specific safety reasons or a request from a regulatory authority.)
A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Compare Fulvestrant Plus BPI-16350 or Plus Placebo in Patients With HR+, HER2- Locally Advanced, Recurrent or Metastatic Breast Cancer With Disease Progression Following Endocrine Therapy[NCT05433480]	Phase 3	274 participants (Actual)	Interventional	2022-05-25	Active, not recruiting
Randomized Phase 2 Trial of Seribantumab Plus Fulvestrant in Postmenopausal Women With Hormone Receptor-positive, Heregulin Positive (HRG+), HER2 Negative Metastatic Breast Cancer (Merrimack Pharmaceuticals Inc.)[NCT03241810]	Phase 2	22 participants (Actual)	Interventional	2017-08-15	Terminated(stopped due to Merrimack Inc. terminated the trial early due to business decision)
MONARCH 2: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of Fulvestrant With or Without Abemaciclib, a CDK4/6 Inhibitor, for Women With Hormone Receptor Positive, HER2 Negative Locally Advanced or Metastatic Breast Cancer[NCT02107703]	Phase 3	669 participants (Actual)	Interventional	2014-07-22	Active, not recruiting
Comparison in the Change of Proliferation Index Between Fulvestrant and Tamoxifen in Cyclin D1 +, Estrogen Receptor + Breast Cancer[NCT02936206]	Phase 1	2 participants (Actual)	Interventional	2016-10-31	Terminated(stopped due to low accrual rate)
A Phase II Randomized Trial of Fulvestrant and Anastrozole as Consolidation Therapy in Postmenopausal Women With Advanced Non-small Cell Lung Cancer Who Have Received First-line Platinum-based Chemotherapy With or Without Bevacizumab[NCT00932152]	Phase 2	3 participants (Actual)	Interventional	2010-09-30	Terminated(stopped due to Poor enrollment/suspended to accrual; will close per AstraZeneca request)
DETECT V / CHEVENDO A Multicenter, Randomized Phase III Study to Compare Chemo- Versus Endocrine Therapy in Combination With Dual HER2-targeted Therapy of Herceptin® (Trastuzumab) and Perjeta® (Pertuzumab) Plus Kisqali® (Ribociclib) in Patients With HER2 [NCT02344472]	Phase 3	270 participants (Anticipated)	Interventional	2015-09-30	Recruiting
A Randomized Phase I/II Trial of Fulvestrant and Abemaciclib in Combination With Copanlisib (FAC) Versus Fulvestrant and Abemaciclib Alone (FA) for Endocrine-Resistant, Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer (FAC vs FA)[NCT03939897]	Phase 1/Phase 2	204 participants (Anticipated)	Interventional	2020-06-17	Active, not recruiting
An Open, Multicenter Phase Ⅰb/Ⅱ Clinical Study of SHR-A1811 Combined With Dalpiciclib, Fulvestrant, Bevacizumab or Letrozole/Anastrozole in Patients With HER2 Low Advanced or Metastatic Breast Cancer.[NCT05792410]	Phase 1/Phase 2	300 participants (Anticipated)	Interventional	2023-04-30	Not yet recruiting
Multicenter, Randomized Trial to Evaluate Efficacy and Safety of Bevacizumab in Combination With Endocrine Treatment vs Endocrine Alone, in Postmenopausal With Advanced or Metastatic Cancer With Indication of Hormonotherapy as First-line[NCT00545077]	Phase 3	380 participants (Actual)	Interventional	2007-11-06	Completed
Open-label, Multicentre, Phase Ib Dose-escalation Study of MEN1611, a PI3K Inhibitor Combined With Trastuzumab With or Without Fulvestrant, in Subjects With PIK3CA Mutated HER2 Positive Locally Recurrent Unresectable (Advanced) or Metastatic (a/m) Breast [NCT03767335]	Phase 1	62 participants (Actual)	Interventional	2018-07-19	Active, not recruiting
The Neoadjuvant Combined Hormone Therapy in Premenopausal Women With Locally Advanced ER+/HER2- Breast Cancer[NCT04753177]	Phase 2/Phase 3	120 participants (Anticipated)	Interventional	2021-01-28	Active, not recruiting
A Phase II Open Label, Umbrella Study Evaluating the Efficacy and Safety of Fulvestrant Plus DNA Damage Repair Inhibitors in Hormone Receptor-positive Advanced Breast Cancer After a CDK4/6 Inhibitor[NCT05536128]	Phase 2	64 participants (Anticipated)	Interventional	2022-12-31	Not yet recruiting
A Multiple Parallel Cohort, Multi-centre Phase IIa Trial Aiming to Provide Proof of Principle Efficacy for Designated Targeted Therapies in Patients With Advanced Breast Cancer Where the Targetable Mutation is Identified Through ctDNA[NCT03182634]	Phase 2	1,150 participants (Anticipated)	Interventional	2016-12-15	Recruiting
Phase II Randomized Trial of Faslodex and Herceptin, Alone and Combined, in the First - Line Treatment of Hormone Receptor-Positive, HER-2/Neu-Overexpressing Metastatic Breast Cancer[NCT00138125]	Phase 2	2 participants (Actual)	Interventional	2005-04-30	Terminated(stopped due to Due to low accrual)
Study of Efficacy of Everolimus Combined With First-line Endocrine Therapy for HR+/HER2- (Open, Randomized, Phase II )[NCT05949541]	Phase 2	265 participants (Anticipated)	Interventional	2023-07-31	Not yet recruiting
A Phase Ib, Open-label, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of HS-10352 in Combination With Fulvestrant in Patients With Hormone Receptor (HR) Positive, Human Epidermal Growth Factor 2 (HER2)-Negative, PIK3CA[NCT05504213]	Phase 1	224 participants (Anticipated)	Interventional	2022-01-12	Recruiting
A Multicenter, Open-label, Phase Ib Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of CYH33 in Combination With Endocrine Therapy With or Without Palbociclib in Patients With PIK3CA Mutant, HR+, HER2- Advanced Breast[NCT04856371]	Phase 1	228 participants (Anticipated)	Interventional	2021-04-30	Not yet recruiting
Analysis of Therapy Sequence in Women With Hormone Receptor-positive, HER2-negative Metastatic Breast Cancer in Russia: A Multicentre Retrospective Observational Real-life Study.[NCT04852081]		1,000 participants (Anticipated)	Observational	2021-01-01	Recruiting
Combined Fulvestrant and Anastrozole as Neo-adjuvant Endocrine Therapy in Postmenopausal Women With Hormone Receptor Positive Invasive Breast Cancer[NCT00921115]	Phase 2	42 participants (Actual)	Interventional	2009-05-31	Completed
A Phase II, Open-Label, Randomized Study of GDC-0810 Versus Fulvestrant in Postmenopausal Women With Advanced or Metastatic ER+ /HER2- Breast Cancer Resistant to Aromatase Inhibitor Therapy[NCT02569801]	Phase 2	71 participants (Actual)	Interventional	2015-12-04	Terminated(stopped due to The Sponsor decided to halt the development of GDC-0810, but not due to any safety concerns.)
A Phase 1b/2 Study of Safety and Efficacy of MLN0128 (Dual TORC1/2 Inhibitor) in Combination With Exemestane or Fulvestrant Therapy in Postmenopausal Women With ER+/HER2- Advanced or Metastatic Breast Cancer That Has Progressed on Treatment With Everolimu[NCT02049957]	Phase 2	118 participants (Actual)	Interventional	2014-02-13	Completed
A Randomized, Open-label, Multicenter, Two-arm, Phase III Study to Evaluate Efficacy and Quality of Life in Patients With Metastatic Hormone Receptor-positive HER2-negative Breast Cancer Receiving Ribociclib in Combination With Endocrine Therapy or Chemot[NCT03462251]	Phase 3	41 participants (Actual)	Interventional	2018-05-24	Completed
A Randomized, Multicenter, Open-label, Phase II Trial to Evaluate the Efficacy and Safety of Palbociclib in Combination With Fulvestrant or Letrozole in Patients With HER2 Negative, ER+ Metastatic Breast Cancer[NCT02491983]	Phase 2	486 participants (Actual)	Interventional	2015-08-31	Completed
An Open-Label, Phase 2 Basket Study of Neratinib in Patients With Solid Tumors With Somatic Activating HER Mutations[NCT01953926]	Phase 2	582 participants (Actual)	Interventional	2013-09-30	Completed
Bevacizumab Plus Paclitaxel Optimization Study With Interventional Maintenance Endocrine Therapy in Advanced or Metastatic ER-positive HER2-negative Breast Cancer -BOOSTER Trial, a Multicenter Randomized Phase II Study-[NCT01989780]	Phase 2	160 participants (Actual)	Interventional	2014-01-31	Completed
Alternate Approaches for Clinical Stage II or III Estrogen Receptor Positive Breast Cancer Neoadjuvant Treatment (ALTERNATE) in Postmenopausal Women: A Phase III Study[NCT01953588]	Phase 3	1,473 participants (Actual)	Interventional	2013-12-13	Active, not recruiting
Phase II Trial of Exemestane (Aromasin) in Combination With Fulvestrant (Faslodex) in Postmenopausal Women With Hormone Sensitive Advanced Breast Cancer[NCT00201864]	Phase 2	40 participants (Actual)	Interventional	2005-09-30	Completed
A Phase I, Open-Label, Dose-Escalation Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0077 as a Single Agent in Patients With Locally Advanced or Metastatic PIK3CA-Mutant Solid Tumors and in Combination With Endocrine and Targeted [NCT03006172]	Phase 1	256 participants (Anticipated)	Interventional	2016-12-13	Recruiting
Phase II Open Label Study of Everolimus in Combination With Anti-estrogen Therapy in Hormone Receptor-Positive HER2-Negative Advanced Breast Cancer[NCT02291913]	Phase 2	48 participants (Actual)	Interventional	2014-12-18	Completed
An Exploratory Study of Surufatinib Combined With Chidamide and Fulvestrant in HR Positive Unresectable Metastatic Breast Cancer Refractory to Endocrine Therapy[NCT05186545]	Phase 2	63 participants (Anticipated)	Interventional	2022-07-01	Recruiting
A Phase III, Double-Blind, Placebo-Controlled, Randomized Study of Taselisib Plus Fulvestrant Versus Placebo Plus Fulvestrant in Postmenopausal Women With Estrogen Receptor-Positive and HER2-Negative Locally Advanced or Metastatic Breast Cancer Who Have D[NCT02340221]	Phase 3	631 participants (Actual)	Interventional	2015-04-09	Terminated(stopped due to The Sponsor discontinued the manufacturing and development of taselisib due to modest clinical benefit and limited tolerability.)
A Phase 2, Randomized, Open-label, Two-arm Study to Assess the Efficacy and Safety of the Epigenetic Modifying Effects of CC-486 (Oral Azacitidine) in Combination With Fulvestrant in Postmenopausal Women With ER+, HER2- Metastatic Breast Cancer Who Have P[NCT02374099]	Phase 2	97 participants (Actual)	Interventional	2015-03-13	Terminated
A Phase 3 Randomized, Open-Label Study Of OP-1250 Monotherapy vs Standard of Care for the Treatment of ER+, HER2- Advanced or Metastatic Breast Cancer Following Endocrine and CDK 4/6 Inhibitor Therapy (OPERA-01)[NCT06016738]	Phase 3	510 participants (Anticipated)	Interventional	2023-10-10	Recruiting
Multicenter, Single-arm, Open Clinical Study of Chidamide in Combination With Fulvestrant in HR+/HER2-advanced Breast Cancer That Has Failed Prior CDK4/6 Inhibitor Combined With Aromatase Inhibitor Therapy[NCT05808582]	Phase 2	60 participants (Anticipated)	Interventional	2023-05-01	Not yet recruiting
An Open Label, Dose Escalation, Safety, and Pharmacokinetic Study of CFI-402257 Administered Orally to Patients With Advanced Solid Tumors[NCT02792465]	Phase 1	52 participants (Anticipated)	Interventional	2016-11-11	Active, not recruiting
A Phase I/II Study Evaluating M1774, an ATR Inhibitor, in Combination With Fulvestrant in Hormone Receptor-positive and HER2-negative, Advanced Breast Cancers, Resistant to CDK4/6 Inhibitor Plus Aromatase Inhibitor-based Endocrine Treatment[NCT05986071]	Phase 1/Phase 2	57 participants (Anticipated)	Interventional	2024-04-01	Not yet recruiting
A Multicenter, Open-Label, Randomized-Controlled Study of Abemaciclib, a CDK4 and 6 Inhibitor, in Combination With Fulvestrant Compared to Chemotherapy in Women With HR Positive, HER2 Negative Metastatic Breast Cancer With Visceral Metastases[NCT04031885]	Phase 4	4 participants (Actual)	Interventional	2019-08-14	Terminated(stopped due to Business decision based on the inability to enroll subjects into the trial)
A Phase Ib Trial of Fulvestrant, Palbociclib (CDK4/6 Inhibitor) and Erdafitinib (JNJ- 42756493,Pan-FGFR Tyrosine Kinase Inhibitor) in ER+/HER2-/FGFR-Amplified Metastatic Breast Cancer (MBC)[NCT03238196]	Phase 1	35 participants (Actual)	Interventional	2017-08-18	Active, not recruiting
A randoMized phAse II trIal of fulvestraNt wiTh or Without Ribociclib After Progression on AntI-estrogeN Therapy Plus Cyclin-dependent Kinase 4/6 Inhibition in Patients With Unresectable or Metastatic Hormone Receptor +, HER2 - Breast Cancer (MAINTAIN Tri[NCT02632045]	Phase 2	137 participants (Actual)	Interventional	2016-03-31	Active, not recruiting
Estrogen Receptor Antagonist in Patients With Pulmonary Arterial Hypertension[NCT02911844]	Phase 2	5 participants (Actual)	Interventional	2017-04-10	Completed
Genetically-informed Therapy for ER+ Breast Cancer in a Post-CDK4/6 Inhibitor Setting: a Phase II Umbrella Study (GERTRUDE)[NCT05933395]	Phase 2	135 participants (Anticipated)	Interventional	2023-10-10	Recruiting
Phase II Study of the Combination of Pembrolizumab, Letrozole, and Palbociclib in Postmenopausal Patients With Newly Diagnosed Metastatic Estrogen Receptor Positive Breast Cancer[NCT02778685]	Phase 2	40 participants (Actual)	Interventional	2016-09-30	Active, not recruiting
Phase II Trial of Capecitabine in Combination With Fulvestrant for Postmenopausal Women With Hormone Receptor Positive Metastatic Breast Cancer[NCT00534417]	Phase 2	41 participants (Actual)	Interventional	2007-10-31	Completed
Study Evaluating Hemay022 in Combination With Endocrine Therapy In Subjects With ER Positive and HER2 Positive Advanced Breast Cancer[NCT03308201]	Phase 1	48 participants (Anticipated)	Interventional	2017-10-16	Recruiting
A Phase II Study of Neratinib Alone and in Combination With Fulvestrant in Metastatic HER2 Non-amplified But HER2 Mutant Breast Cancer[NCT01670877]	Phase 2	56 participants (Actual)	Interventional	2012-12-11	Completed
Phase 1/2 Safety, Pharmacokinetic, and Antitumor Activity Study of G1T38 in Combination With Fulvestrant in Patients With Hormone Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer After Endocrine Failure[NCT02983071]	Phase 1/Phase 2	102 participants (Anticipated)	Interventional	2017-01-31	Active, not recruiting
Single Arm Phase 2 Study of Metformin and Simvastatin in Addition to Fulvestrant in Metastatic Estrogen Receptor Positive Breast Cancer[NCT03192293]	Phase 2	28 participants (Anticipated)	Interventional	2017-01-20	Recruiting
A Phase II Trial of Cabozantinib in Women With Metastatic Hormone-Receptor-Positive Breast Cancer With Involvement of Bone[NCT01441947]	Phase 2	68 participants (Actual)	Interventional	2011-10-31	Active, not recruiting
Clinical Trial to Evaluate Safety and Anti-tumor Activity of AKT Inhibitor, Ipatasertib,With Endocrine Therapy With/Without CDK 4/6 Inhibitor for Patients With Metastatic Hormone Receptor Positive Breast Cancer (TAKTIC)[NCT03959891]	Phase 1	77 participants (Actual)	Interventional	2019-05-30	Active, not recruiting
Fulvestrant Followed by Everolimus Plus Exemestane vs Examestane and Everolimus Followed by Fulvestrant in Postmenopausal Women With HR+ and HER2- Locally Advanced (LABC) or Metastatic Breast Cancer (MBC) Previously Treated With NSAI[NCT02404051]	Phase 3	745 participants (Anticipated)	Interventional	2015-12-31	Recruiting
An International Multicenter Phase II Trial of Durvalumab (MEDI4736) Plus OLAparib Plus Fulvestrant in Metastatic or Locally Advanced ER-positive, HER2-negative Breast Cancer Patients Selected Using Criteria That Predict Sensitivity to Olaparib[NCT04053322]	Phase 2	172 participants (Actual)	Interventional	2019-08-26	Active, not recruiting
NANT Colorectal Cancer (CRC) Vaccine: Combination Immunotherapy in Subjects With Recurrent or Metastatic CRC[NCT03169777]	Phase 1/Phase 2	0 participants (Actual)	Interventional	2018-08-31	Withdrawn(stopped due to Trial not initiated)
A Phase I, Open-Label, Non-randomised, Single Centre Study of the Absorption, Metabolism, Excretion and Pharmacokinetics of AZD2014 After a Single Oral Dose of [14C]AZD2014, Followed by Multiple Doses of AZD2014 Either As Monotherapy or In Combination Wit[NCT02640755]	Phase 1	4 participants (Actual)	Interventional	2016-01-28	Completed
A Phase III, Multicenter, Open-label Study of Ribociclib vs. Palbociclib in Patients With Advanced Hormone Receptor-positive/HER2-negative/HER2-Enriched Breast Cancer - HARMONIA Trial[NCT05207709]	Phase 3	456 participants (Anticipated)	Interventional	2022-03-28	Recruiting
A Single Arm, Tolerability and Safety Phase IV Study of Fulvestrant(Faslodex® ) as 2nd Line and Later Therapy in Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer[NCT02447328]	Phase 4	83 participants (Actual)	Interventional	2015-05-29	Completed
A Phase Ib/III Study to Evaluate the Efficacy and Safety of Afuresertib Plus Fulvestrant in Patients With Locally Advanced or Metastatic HR+/HER2- Breast Cancer Who Failed Standard of Care Therapies[NCT04851613]	Phase 1	20 participants (Anticipated)	Interventional	2022-02-18	Active, not recruiting
A Pilot Study Evaluating Megestrol Acetate Modulation in Advanced Breast Cancer With Positive Hormonal Receptor[NCT03024580]	Phase 2	20 participants (Anticipated)	Interventional	2017-03-06	Recruiting
A Phase II Trial of Tipifarnib (R115777, Zarnestra™) in Combination With Fulvestrant (Faslodex®) in Postmenopausal Hormone Receptor-Positive Breast Cancer[NCT00082810]	Phase 2	33 participants (Actual)	Interventional	2004-03-31	Completed
PHASE 1B STUDY TO ASSESS THE SAFETY, TOLERABILITY, AND CLINICAL ACTIVITY OF GEDATOLISIB IN COMBINATION WITH PALBOCICLIB AND EITHER LETROZOLE OR FULVESTRANT IN WOMEN WITH METASTATIC OR LOCALLY ADVANCED/RECURRENT BREAST CANCER (MBC)[NCT02684032]	Phase 1	141 participants (Actual)	Interventional	2016-06-14	Completed
A Phase 1b/2 Randomised Placebo Controlled Trial of Fulvestrant +/- AZD5363 in Postmenopausal Women With Advanced Breast Cancer Previously Treated With a Third Generation Aromatase Inhibitor[NCT01992952]	Phase 1/Phase 2	149 participants (Actual)	Interventional	2014-05-31	Active, not recruiting
Tucidinostat Combined With Metronomic Capecitabine and Endocrine Therapy for Advanced HR-positive, HER2-negative Breast Cancer After CDK4/6 Inhibitor：a Prospective, Single-arm, Phase II Clinical Trial.[NCT05411380]	Phase 2	73 participants (Anticipated)	Interventional	2022-10-03	Recruiting
A Phase II Multi-Institutional Study of Concurrent Radiotherapy, Palbociclib, and Hormone Therapy for Treatment of Bone Metastasis in Breast Cancer Patients[NCT03691493]	Phase 2	38 participants (Actual)	Interventional	2019-02-08	Completed
A Pilot Phase II Study of Neoadjuvant Fulvestrant Plus Abemaciclib in Women With Advanced Low Grade Serous Carcinoma[NCT03531645]	Phase 2	18 participants (Actual)	Interventional	2019-08-13	Active, not recruiting
INTERACT- Integrated Evaluation of Resistance and Actionability Using Circulating Tumor DNA in HR Positive Metastatic Breast Cancers[NCT04256941]	Phase 2	4 participants (Actual)	Interventional	2019-05-31	Completed
Phase II Study of Fulvestrant in Combination With Abemaciclib in Hormone Receptor Positive Adenocarcinoma of Endometrium[NCT03643510]	Phase 2	25 participants (Anticipated)	Interventional	2018-08-21	Recruiting
Phase II Trial of Fulvestrant in Treatment of Recurrent Ovarian Carcinoma[NCT00617188]	Phase 2	26 participants (Actual)	Interventional	2007-06-30	Completed
Phase 2 Study of MCLA-128-based Combinations in Metastatic Breast Cancer (MBC): MCLA-128/Trastuzumab/Chemotherapy in HER2-positive MBC and MCLA-128/Endocrine Therapy in Estrogen Receptor Positive and Low HER2 Expression MBC[NCT03321981]	Phase 2	101 participants (Actual)	Interventional	2018-01-15	Active, not recruiting
1303GCC: Phase II Study of Trastuzumab and Pertuzumab Alone and in Combination With Hormonal Therapy or Chemotherapy in Women Aged 60 and Over With HER2/Neu Overexpressed Locally Advanced and/or Metastatic Breast Carcinoma[NCT02000596]	Phase 2	2 participants (Actual)	Interventional	2014-01-31	Terminated(stopped due to funding withdrawn by sponsor)
A First-in-Human Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, as a Single Agent in Advanced Solid Tumor Patients and in Combination With Fulvestrant in Patients With Advanced Breast Cancer[NCT05216432]	Phase 1	400 participants (Anticipated)	Interventional	2021-12-08	Recruiting
A Phase II Study of the Efficacy and Tolerability of Fulvestrant Plus Anlotinib in HR(+)/HER2(-) Metastatic Breast Cancer Patients With FGFR Mutation[NCT04936295]	Phase 2	61 participants (Anticipated)	Interventional	2021-06-16	Recruiting
A PHASE 1 OPEN-LABEL, DOSE ESCALATION STUDY EVALUATING THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF ENZALUTAMIDE (FORMERLY MDV3100) IN PATIENTS WITH INCURABLE BREAST CANCER[NCT01597193]	Phase 1	101 participants (Actual)	Interventional	2012-04-30	Completed
A Phase 1B Trial Evaluating the Safety of Ribociclib, Tucatinib, and Trastuzumab in Patients With Metastatic, HER2+ Breast Cancer and a Multicenter, Randomized, Open-Label, Phase 2 Study of Preoperative Treatment With Ribociclib,Ttrastuzumab, Tucatinib, a[NCT05319873]	Phase 1/Phase 2	18 participants (Anticipated)	Interventional	2022-04-07	Recruiting
A Phase II, Single Arm, Non-randomized Study of Alpelisib (BYL719) in Combination With Continued Endocrine Therapy Following Progression on Endocrine Therapy in Hormone Receptor Positive, HER2 Negative, PIK3CA Mutant Metastatic Breast Cancer[NCT04762979]	Phase 2	44 participants (Anticipated)	Interventional	2021-02-12	Recruiting
A Phase Ib Dose Escalation Study of the Combination of LEE011 With Letrozole and Dose Expansion of LEE011 With Hormonal Therapy for the Treatment of Pre-(With Goserelin) and Postmenopausal Women With Hormone Receptor Positive, HER2-negative, Advanced Brea[NCT02333370]	Phase 1	88 participants (Actual)	Interventional	2015-02-04	Completed
A Phase II Trial of Open-Label Bevacizumab Administered With Anastrozole or Fulvestrant as First-Line Therapy in Postmenopausal Hormone Receptor- Positive Metastatic Breast Cancer (With Trastuzumab in HER2-Positive Patients)[NCT00405938]	Phase 2	79 participants (Actual)	Interventional	2006-11-30	Completed
Assessment of Treatment Response With Faslodex® (500 mg) in Standard Clinical Practice Through a Retrospective Study[NCT01509625]		272 participants (Actual)	Observational	2012-01-31	Completed
A Phase II Open-Label Study of Sorafenib Plus Fulvestrant as Salvage Therapy for Hormone Receptor Positive Metastatic Breast Cancer Failing Prior Aromatase Inhibitor Treatment[NCT00722072]	Phase 2	12 participants (Actual)	Interventional	2008-07-31	Terminated(stopped due to Sponsor pulled funding and low accrual)
Evaluate Efficacy and Safety of CDK4/6 Inhibitor Palbociclib in Combination With Fulvestrant Versus Fulvestrant in Female Patients With HR+/HER2- Advanced Breast Cancer: A Real-world Multicenter Observational Study in China[NCT04526028]		612 participants (Anticipated)	Observational	2019-09-13	Recruiting
A Liquid-biopsy Informed Platform Trial to Evaluate Treatment in CDK4/6-inhibitor Resistant ER+/HER2- Metastatic Breast Cancer[NCT05601440]	Phase 2	484 participants (Anticipated)	Interventional	2023-06-13	Recruiting
Randomized, Double-Blind, Placebo-Controlled Phase II Trial of Fulvestrant (Faslodex) Plus Everolimus in Post-Menopausal Patients With Hormone-Receptor Positive Metastatic Breast Cancer Resistant to Aromatase Inhibitor Therapy[NCT01797120]	Phase 2	131 participants (Actual)	Interventional	2013-05-31	Completed
Endocrine Treatment Alone as Primary Treatment for Elderly Patients With Estrogen Receptor Positive Operable Breast Cancer and Low Recurrence Score[NCT02476786]	Phase 2	50 participants (Anticipated)	Interventional	2017-01-17	Recruiting
Multicenter Study of Fulvestrant (Faslodex®) in Early, Recurrent Prostate Cancer Following Local Therapy: A Phase II Trial[NCT00217464]	Phase 2	17 participants (Actual)	Interventional	2004-06-30	Terminated(stopped due to Closed for futility)
A Phase III Randomized, Double Blind, Placebo Controlled Study of BKM120 With Fulvestrant, in Postmenopausal Women With Hormone Receptor-positive HER2-negative AI Treated, Locally Advanced or Metastatic Breast Cancer Who Progressed on or After mTOR Inhibi[NCT01633060]	Phase 3	432 participants (Actual)	Interventional	2012-10-03	Terminated(stopped due to Novartis decided not to pursue further development of buparlisib program (assessment of moderate PFS benefit with know, but manageable, buparlisib profile).)
An Open-Label, Phase Ib/II Clinical Trial Of Cdk 4/6 Inhibitor, Ribociclib (Lee011), In Combination With Trastuzumab Or T-Dm1 For Advanced/Metastatic Her2-Positive Breast Cancer.[NCT02657343]	Phase 1/Phase 2	25 participants (Actual)	Interventional	2016-03-09	Completed
A Randomized Phase II Trial of Fulvestrant and Palbociclib in Combination With Copanlisib (FPC) Versus Fulvestrant and Palbociclib Alone (FP) for Endocrine Resistant, Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer (FPC vs FP)[NCT03377101]	Phase 2	0 participants (Actual)	Interventional	2018-08-07	Withdrawn(stopped due to change in study design.)
A Phase II, Randomized, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of GDC-9545 Compared With Physician's Choice of Endocrine Monotherapy in Patients With Previously Treated Estrogen Receptor-Positive, HER2-Negative Locally Advanced o[NCT04576455]	Phase 2	303 participants (Actual)	Interventional	2020-11-27	Active, not recruiting
A Randomised Trial of Early Detection of Molecular Relapse With Circulating Tumour DNA Tracking and Treatment With Palbociclib Plus Fulvestrant Versus Standard Endocrine Therapy in Patients With ER Positive HER2 Negative Breast Cancer[NCT04985266]	Phase 2	1,100 participants (Anticipated)	Interventional	2022-03-30	Recruiting
Phase I Dose-Escalation Study of Combination of Gedatolisib (a Dual Inhibitor of PI3-K and mTOR) With Palbociclib and Faslodex in the Neoadjuvant Setting in Previously Untreated Patients With ER+/HER2- Breast Cancer[NCT02626507]	Phase 1	18 participants (Anticipated)	Interventional	2016-01-31	Active, not recruiting
Fulvestrant Alone Versus Fulvestrant and Everolimus Versus Fulvestrant, Everolimus and Anastrozole: A Phase III Randomized Placebo-Controlled Trial in Postmenopausal Patients[NCT02137837]	Phase 3	37 participants (Actual)	Interventional	2014-05-31	Terminated(stopped due to lack of accrual)
A Phase 1, Randomized, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Fulvestrant (Test vs. Reference) Following Intramuscular Administration to the Gluteal Muscle in Healthy Female Subjects[NCT03324061]	Phase 1	600 participants (Actual)	Interventional	2017-11-30	Completed
A Phase III Randomized, Double Blind Placebo Controlled Study of BKM120 With Fulvestrant, in Postmenopausal Women With Hormone Receptor-positive HER2-negative Locally Advanced or Metastatic Breast Cancer Which Progressed on or After Aromatase Inhibitor Tr[NCT01610284]	Phase 3	1,147 participants (Actual)	Interventional	2012-08-07	Completed
Efficacy of Oral Regorafenib Combined With Intra-muscular Injection of Fulvestrant in Patients With Recurrent Low-grade Serous Ovarian Cancer: A Phase II Single Arm Trial[NCT05113368]	Phase 2	31 participants (Anticipated)	Interventional	2022-06-28	Recruiting
Open Label Sequential Dosing Single Ascending Dose of Four Cohort and Multiple Dose of One Cohort Pharmacokinetics Tolerability and Safety of Fulvestrant Injection as Test Product KSHN001034 vs Reference Product FASLODEX®[NCT06074757]	Phase 1	48 participants (Actual)	Interventional	2023-03-01	Completed
A Randomized, Phase II Study for Premenopausal Metastatic or Locally Advanced Breast Cancer Patients: Capivasertib, Goserelin, Fulvestrant With/Without Durvalumab, Versus Goserelin, Fulvestrant, and Durvalumab, Versus Goserelin/ Fulvestrant.[NCT05720260]	Phase 2	56 participants (Anticipated)	Interventional	2023-01-17	Recruiting
NANT Head and Neck Squamous Cell Carcinoma (HNSCC) Vaccine: Combination Immunotherapy in Subjects With HNSCC Who Have Progressed on or After Chemotherapy and Anti-programmed Cell Death Protein 1 (PD-1)/Programmed Death-ligand 1 (PD-L1) Therapy[NCT03169764]	Phase 1/Phase 2	0 participants (Actual)	Interventional	2017-12-31	Withdrawn(stopped due to Trial not initiated)
An Open Label, Multi-center, Extension Study to Evaluate Long-term Safety and Tolerability of Dovitinib in Patients With Solid Tumors, Who Continue to Receive Treatment With Dovitinib (TKI258) in Novartis-sponsored, Single Agent Dovitinib Studies, Which H[NCT02116803]	Phase 2/Phase 3	12 participants (Actual)	Interventional	2014-05-28	Completed
Phase II Study of Everolimus Beyond Progression in Postmenopausal Women With Advanced, Hormone Receptor Positive Breast Cancer[NCT02269670]	Phase 2	3 participants (Actual)	Interventional	2014-11-25	Terminated(stopped due to Slow to accrual)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Determination (All Subjects Treated (AST) Set): Safety and Toxicity by Assessment of the Frequency of Grade I-IV Haematological and Non-haematological Toxicities

number of adverse events (NCT00334295)
Timeframe: ICF to Last Patient Out (LPO)

Intervention	adverse events (Number)
Fulvestrant	169

Determination (for ITT (Intet-to-Treat Set): Efficacy of a Monthly Administration of Fulvestrant in Patients With Recurrent or Metastatic Endometrial Carcinoma by Assessment of the Clinical Tumour Response After 3 Injections of Fulvestrant

Number of patients with Complete Remission (CR) and Partial Response (PR), as determined by an independent expert panel according to the WHO response criteria. (NCT00334295)
Timeframe: up to 1 year

Intervention	participants (Number)
Fulvestrant	5

Determination (for ITT Set): Median Survival

median overall survival (OS) (NCT00334295)
Timeframe: ICF to the date of death

Intervention	months (Median)
Fulvestrant	16.7

Evaluation (Patient-reported): Change From Baseline in Health-related Quality of Life (HR-QoL) at 12 Months (12 Visits)

Patient-reported FACT-EN questionaire. Presented is the change from baseline after 12 visits/12 months. The overall total score of 43 single items was transformed to a scale from 0 to 100 (0 = worst level of well-being; 100 = highest level of well-being). (NCT00334295)
Timeframe: ICF (Baseline) up to 12 months (12 visits)

Intervention	units on a scale (Mean)
Fulvestrant	6.0

Time to Progression of Disease (TTP-Time To Progression, for ITT Set)

median TTP (NCT00334295)
Timeframe: ICF (Informed Consent Form completed) to the date of objective progression or death (by any cause in the absence of progression)

Intervention	months (Median)
Fulvestrant	3.1

Clinical Benefit Rate

A Clinical Benefit (CB) responder is defined as a patient having a best overall response of either complete response (CR), partial response (PR) or stable disease (SD) for at least 24 weeks evaluated according to modified RECIST. The Clinical Benefit Rate is the percentage of patients with CB. (NCT00274469)
Timeframe: From randomisation to data cut off (DCO) for primary analysis. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007 respectively. The DCO for primary analysis was on 10th Jan 2008, 6 months after the last patient was enrolled.

Intervention	Percentage of Participants (Number)
Fulvestrant 500 mg	72.5
Anastrozole 1 mg	67.0

Objective Response Rate

For each patient with measurable disease at baseline, the determination of the overall response for each visit was carried out using a SAS program per Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete Response (CR): Disappearance of all target lesion (TL) and non-target lesions (NTLs) and no new lesions. Partial Response (PR): At least a 30% decrease in the sum of longest diameter of TLs (compared to baseline), no progression of NTLs and no new lesions. Objective response rate is defined as percentage of patients with either CR or PR. (NCT00274469)
Timeframe: From randomisation to data cut off (DCO) for primary analysis. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007 respectively. The DCO for primary analysis was on 10th Jan 2008, 6 months after the last patient was enrolled.

Intervention	Percentage of Participants (Number)
Fulvestrant 500 mg	36.0
Anastrozole 1 mg	35.5

Overall Survival

Time from randomization to death (any cause) (NCT00274469)
Timeframe: From randomization to data cut off (DCO) for 65% OS analysis. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007 respectively. The DCO for 65% OS analysis was on 15 Jul 2014, 7 years after the last patient was enrolled.

Intervention	Month (Median)
Fulvestrant 500 mg	54.1
Anastrozole 1 mg	48.4

Time to Progression (Investigator Assessed)

Time from randomization to disease progression (investigator assessed) or death from any cause. Progression was defined by investigator opinion, as patients did not have formal RECIST visits in the follow-up period after the data cut off for the primary analysis of the study. (NCT00274469)
Timeframe: From randomisation to data cut off (DCO) for 75% treatment failure. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007. The DCO for 75% treatment failure was on 26 Mar 2010, 32 months after the last patient was enrolled.

Intervention	Day (Median)
Fulvestrant 500 mg	712
Anastrozole 1 mg	400

Time to Progression

Time from randomization until earlier of disease progression or death. Progression was defined according to RECIST: a patient is determined to have progressed if they have progression of target lesions, clear progression of existing non-target lesions, or the appearance of one or more new lesions. Progression of target lesions is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum of LD recorded. Kaplan-Meier estimates of median for each treatment are reported. (NCT00274469)
Timeframe: From randomisation to data cut off (DCO) for primary analysis. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007 respectively. The DCO for primary analysis was on 10th Jan 2008, 6 months after the last patient was enrolled.

Intervention	Day (Median)
Fulvestrant 500 mg	NA
Anastrozole 1 mg	381

Time to Treatment Failure

Time from randomization to treatment discontinuation (NCT00274469)
Timeframe: From randomisation to data cut off (DCO) for 75% treatment failure. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007. The DCO for 75% treatment failure was on 26 Mar 2010, 32 months after the last patient was enrolled.

Intervention	Day (Median)
Fulvestrant 500 mg	536
Anastrozole 1 mg	387

Disease Control Rate (DCR)

DCR was defined, per RECIST 1.1, as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) or Stable Disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD]. (NCT02761694)
Timeframe: Up to approximately 116 weeks

Intervention	Percentage of Participants (Number)
Part 1: Vevorisertib 5 mg QD	0
Part 1: Vevorisertib 10 mg QD	0
Part 1: Vevorisertib 20 mg QD	100.0
Part 1: Vevorisertib 25 mg QD	100.0
Part 1: Vevorisertib 25 mg QOD	33.3
Part 1: Vevorisertib 50 mg QD	50.0
Part 1: Vevorisertib 75 mg QD	45.8
Part 1: Vevorisertib 100 mg QD	57.1
Part 2: Vevorisertib 50 mg QD Plus Paclitaxel	75.0
Part 2: Vevorisertib 75 mg QD Plus Paclitaxel	33.3
Part 2: Vevorisertib 50 mg QD Plus Fulvestrant	0
Part 2: Vevorisertib 75 mg QD Plus Fulvestrant	50.0

Number of Participants Who Discontinue Study Treatment Due to an AE

An AE is defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with study-drug treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE. (NCT02761694)
Timeframe: Up to approximately 116 weeks

Intervention	Participants (Count of Participants)
Part 1: Vevorisertib 5 mg QD	0
Part 1: Vevorisertib 10 mg QD	1
Part 1: Vevorisertib 20 mg QD	0
Part 1: Vevorisertib 25 mg QD	0
Part 1: Vevorisertib 25 mg QOD	0
Part 1: Vevorisertib 50 mg QD	0
Part 1: Vevorisertib 75 mg QD	3
Part 1: Vevorisertib 100 mg QD	0
Part 2: Vevorisertib 50 mg QD Plus Paclitaxel	1
Part 2: Vevorisertib 75 mg QD Plus Paclitaxel	1
Part 2: Vevorisertib 50 mg QD Plus Fulvestrant	0
Part 2: Vevorisertib 75 mg QD Plus Fulvestrant	1

Number of Participants Who Experience One or More Adverse Events (AEs)

Intervention	Participants (Count of Participants)
Part 1: Vevorisertib 5 mg QD	4
Part 1: Vevorisertib 10 mg QD	4
Part 1: Vevorisertib 20 mg	1
Part 1: Vevorisertib 25 mg QD	3
Part 1: Vevorisertib 25 mg QOD	3
Part 1: Vevorisertib 50 mg QD	3
Part 1: Vevorisertib 75 mg QD	32
Part 1: Vevorisertib 100 mg QD	8
Part 2: Vevorisertib 50 mg QD Plus Paclitaxel	5
Part 2: Vevorisertib 75 mg QD Plus Paclitaxel	5
Part 2: Vevorisertib 50 mg QD Plus Fulvestrant	3
Part 2: Vevorisertib 75 mg QD Plus Fulvestrant	6

Number of Participants With a Dose-Limiting Toxicity (DLT), for the Determination of Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)

DLTs consisted of hematologic or non-hematologic toxicities. Hematologic DLT was any grade (Gr) 4 anemia, Gr 4 neutropenia, Gr 4 thrombocytopenia, Gr 3 lasting >7 days, Gr 3 thrombocytopenia in the presence of bleeding, or ≥ Gr 3 hyperglycemia. Non-hematologic DLT was any Gr 3, 4 or 5 non-hematologic toxicity with the exception of: (1) Gr 3 nausea, vomiting, diarrhea or responding to optimal medical management within 48 hours; (2) alopecia. Per protocol DLTs were analyzed in the first 28-day treatment cycle. The number of participants experiencing DLTs is reported here for all participants who got ≥1 dose of study drug. (NCT02761694)
Timeframe: Cycle 1 (Up to approximately 28 days)

Intervention	Participants (Count of Participants)
Part 1: Vevorisertib 5 mg QD	0
Part 1: Vevorisertib 10 mg QD	0
Part 1: Vevorisertib 20 mg QD	0
Part 1: Vevorisertib 25 mg QD	0
Part 1: Vevorisertib 25 mg QOD	0
Part 1: Vevorisertib 50 mg QD	0
Part 1: Vevorisertib 75 mg QD	1
Part 1: Vevorisertib 100 mg QD	1
Part 2: Vevorisertib 50 mg QD Plus Paclitaxel	0
Part 2: Vevorisertib 75 mg QD Plus Paclitaxel	1
Part 2: Vevorisertib 50 mg QD Plus Fulvestrant	0
Part 2: Vevorisertib 75 mg QD Plus Fulvestrant	0

Objective Response Rate (ORR)

ORR was defined as the percentage of participants who have best response of Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). (NCT02761694)
Timeframe: Up to approximately 116 weeks

Intervention	Percentage of Participants (Number)
Part 1: Vevorisertib 5 mg QD	0
Part 1: Vevorisertib 10 mg QD	0
Part 1: Vevorisertib 20 mg QD	0
Part 1: Vevorisertib 25 mg QD	33.3
Part 1: Vevorisertib 25 mg QOD	0
Part 1: Vevorisertib 50 mg QD	0
Part 1: Vevorisertib 75 mg QD	4.2
Part 1: Vevorisertib 100 mg QD	14.3
Part 2: Vevorisertib 50 mg QD Plus Paclitaxel	50.0
Part 2: Vevorisertib 75 mg QD Plus Paclitaxel	0
Part 2: Vevorisertib 50 mg QD Plus Fulvestrant	0
Part 2: Vevorisertib 75 mg QD Plus Fulvestrant	0

Area Under the Curve From 0-24 Hours (AUC0-24 Hours) of Vevorisertib

AUC0-24hrs was defined as area under the concentration-time curve from time 0 to 24 hours after dose administration. This study was terminated because of business reasons. Due to study termination, pharmacokinetic (PK) testing was prioritized for dosing arms and timepoints that would provide the required data to support programmatic decision-making and subsequent clinical studies. Zero participants analyzed entered in the table indicate data were not generated and no data were available. AUC0-24 is reported as geometric mean with a percent coefficient of variation. (NCT02761694)
Timeframe: Cycle 1 Day 1: predose and 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose; Cycle 1 Day 22: predose and 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose; Cycle 2 Day 1: predose. Cycle = 28 days.

Intervention	hours*ng/mL (Geometric Mean)
	Cycle 1 Day1
Part 1: Vevorisertib 5 mg QD	NA

Area Under the Curve From 0-24 Hours (AUC0-24 Hours) of Vevorisertib

,,,,,

Intervention	hours*ng/mL (Geometric Mean)
	Cycle 1 Day1	Cycle 1 Day 22
Part 1: Vevorisertib 10 mg QD	12.27	67.89
Part 1: Vevorisertib 100 mg QD	786.1	1786
Part 1: Vevorisertib 20 mg QD	42.2	78.5
Part 1: Vevorisertib 25 mg QD	244.1	501.8
Part 1: Vevorisertib 25 mg QOD	128.6	181.2
Part 1: Vevorisertib 50 mg QD	287.5	543.8

Area Under the Curve From 0-24 Hours (AUC0-24 Hours) of Vevorisertib

,,,

Intervention	hours*ng/mL (Geometric Mean)
	Cycle 1 Day1	Cycle 2 Day 1
Part 2: Vevorisertib 75 mg QD Plus Paclitaxel	649.6	1280
Part 2: Vevorisertib 50 mg QD Plus Fulvestrant	449	750.7
Part 2: Vevorisertib 50 mg QD Plus Paclitaxel	391.1	837.2
Part 2: Vevorisertib 75 mg QD Plus Fulvestrant	1115	1948

Area Under the Curve From 0-24 Hours (AUC0-24 Hours) of Vevorisertib

Intervention	hours*ng/mL (Geometric Mean)
	Cycle 1 Day1	Cycle 1 Day 22	Cycle 2 Day 1
Part 1: Vevorisertib 75 mg QD	667.6	1832	2013

Best Overall Response (BOR)

BOR was assessed using RECIST 1.1. Response categories included: CR: disappearance of all target lesions; PR: at least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD): at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD; Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; and Inevaluable: participants who have SD as their best overall response but fail to achieve the protocol-defined duration for SD. Percentage of participants with CR, PR, SD, PD, or inevaluable as a best overall response have been reported. (NCT02761694)
Timeframe: Up to approximately 116 weeks

,,,,,,,,,,,

Intervention	Percentage of Participants (Number)
	Complete Response (CR)	Partial Response (PR)	Stable Disease (SD)	Progressive Disease (PD)	Inevaluable
Part 1: Vevorisertib 10 mg QD	0	0	0	100.0	0
Part 1: Vevorisertib 100 mg QD	0	14.3	42.9	28.6	14.3
Part 1: Vevorisertib 20 mg QD	0	0	100.0	0	0
Part 1: Vevorisertib 25 mg QD	0	33.3	66.7	0	0
Part 1: Vevorisertib 25 mg QOD	0	0	33.3	66.7	0
Part 1: Vevorisertib 5 mg QD	0	0	0	100.0	0
Part 1: Vevorisertib 50 mg QD	0	0	50.0	50.0	0
Part 1: Vevorisertib 75 mg QD	0	4.2	41.7	54.2	0
Part 2: Vevorisertib 50 mg QD Plus Fulvestrant	0	0	0	100.0	0
Part 2: Vevorisertib 50 mg QD Plus Paclitaxel	0	50.0	25.0	0	25.0
Part 2: Vevorisertib 75 mg QD Plus Fulvestrant	0	0	50.0	50.0	0
Part 2: Vevorisertib 75 mg QD Plus Paclitaxel	0	0	33.3	66.7	0

Elimination Half-life (t½) of Vevorisertib

t1/2 was defined as the terminal elimination half-life of drug. This study was terminated because of business reasons. Due to study termination, pharmacokinetic (PK) testing was prioritized for dosing arms and timepoints that would provide the required data to support programmatic decision-making and subsequent clinical studies. Zero participants analyzed entered in the table indicate data were not generated and no data were available. t1/2 is reported as geometric mean with a percent coefficient of variation. (NCT02761694)
Timeframe: Cycle 1 Day 1: predose, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose; Cycle 1 Day 22: predose, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose; Cycle 2 Day 1: predose. Cycle = 28 days.

Intervention	hours (Geometric Mean)
	Cycle 1 Day 1
Part 1: Vevorisertib 20 mg QD	3.68
Part 1: Vevorisertib 5 mg QD	NA
Part 2: Vevorisertib 75 mg QD Plus Paclitaxel	8.909

Elimination Half-life (t½) of Vevorisertib

Intervention	hours (Geometric Mean)
	Cycle 1 Day 22
Part 1: Vevorisertib 10 mg QD	10.12

Elimination Half-life (t½) of Vevorisertib

,,,

Intervention	hours (Geometric Mean)
	Cycle 1 Day 1	Cycle 1 Day 22
Part 1: Vevorisertib 100 mg QD	7.437	24.59
Part 1: Vevorisertib 25 mg QD	15.43	39.33
Part 1: Vevorisertib 25 mg QOD	8.257	21.25
Part 1: Vevorisertib 50 mg QD	15.94	20.03

Elimination Half-life (t½) of Vevorisertib

Intervention	hours (Geometric Mean)
	Cycle 1 Day 1	Cycle 2 Day 1
Part 2: Vevorisertib 50 mg QD Plus Fulvestrant	9.48	28.78
Part 2: Vevorisertib 50 mg QD Plus Paclitaxel	8.920	20.89
Part 2: Vevorisertib 75 mg QD Plus Fulvestrant	9.176	11.46

Elimination Half-life (t½) of Vevorisertib

Intervention	hours (Geometric Mean)
	Cycle 1 Day 1	Cycle 1 Day 22	Cycle 2 Day 1
Part 1: Vevorisertib 75 mg QD	12.39	12.94	22.93

Maximum Plasma Concentration (Cmax) of Vevorisertib

Cmax was defined as the maximum plasma drug concentration. This study was terminated because of business reasons. Due to study termination, pharmacokinetic (PK) testing was prioritized for dosing arms and timepoints that would provide the required data to support programmatic decision-making and subsequent clinical studies. Zero participants analyzed entered in the table indicate data were not generated and no data were available. Cmax is reported as geometric mean with a percent coefficient of variation. (NCT02761694)
Timeframe: Cycle 1 Day 1: predose and 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose; Cycle 1 Day 22: predose and 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose; Cycle 2 Day 1: predose. Cycle = 28 days.

,,,,,,

Intervention	ng/mL (Geometric Mean)
	Cycle 1 Day 1	Cycle 1 Day 22
Part 1: Vevorisertib 10 mg QD	4.820	12.82
Part 1: Vevorisertib 100 mg QD	122.6	207.7
Part 1: Vevorisertib 20 mg QD	15.3	7.79
Part 1: Vevorisertib 25 mg QD	51.39	65.40
Part 1: Vevorisertib 25 mg QOD	22.73	19.49
Part 1: Vevorisertib 5 mg QD	NA	4.154
Part 1: Vevorisertib 50 mg QD	59.79	55.15

Maximum Plasma Concentration (Cmax) of Vevorisertib

,,,

Intervention	ng/mL (Geometric Mean)
	Cycle 1 Day 1	Cycle 2 Day 1
Part 2: Vevorisertib 50 mg QD Plus Fulvestrant	91.7	62.59
Part 2: Vevorisertib 50 mg QD Plus Paclitaxel	29.13	78.36
Part 2: Vevorisertib 75 mg QD Plus Fulvestrant	166.7	138.2
Part 2: Vevorisertib 75 mg QD Plus Paclitaxel	49.11	79.52

Maximum Plasma Concentration (Cmax) of Vevorisertib

Intervention	ng/mL (Geometric Mean)
	Cycle 1 Day 1	Cycle 1 Day 22	Cycle 2 Day 1
Part 1: Vevorisertib 75 mg QD	98.75	225.1	186.8

Clinical Response by RECIST Criteria of Estrogen Receptor Expression

Per response evaluation criteria in Solid Tumors Criteria (RECIST 1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR) >=30% decrease in the sum of the longest diameter of target lesions. Overall Response = CR+PR (NCT00006903)
Timeframe: Every other cycle (every 8 weeks) until disease progression is documented or adverse events preclude further treatment, assessed up to 100 months.

Intervention	Participants (Count of Participants)
	Complete Response	Partial Response	Stable Disease	Increasing Disease	Not Evaluated
Estrogen Receptor Negative	0	0	4	17	1
Estrogen Receptor Positive	1	4	9	17	0

Clinical Response by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Evaluated Every 8 Weeks

"Primary outcome measured according to RECIST v1.0 Best Response:~Complete Response (CR) is disappearance of all target and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart~Disease Progression is at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD or the appearance of new lesions within 8 weeks of study entry.~Partial Response (PR) is at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of nontarget lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required~Stable Disease is any condition not meeting the above criteria.~Indeterminate is defined as having no repeat tumor assessments following initiation of study therapy for reasons unrelated to symptoms or signs of disease." (NCT00006903)
Timeframe: Response was measured every other cycle (every 8 weeks) until disease progression is documented or adverse events preclude further treatment.

Intervention	participants (Number)
	Complete Response	Partial Response	Stable Disease	Disease Progression	Indeterminate
Estrogen Receptor Negative	0	0	4	18	1
Estrogen Receptor Positive	1	4	9	16	0

Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug.

Adverse events at least possibly related to Fulvestrant using Common Terminology Criteria version 3.0 that were grade 3 or higher with the exception of the reported Grade 5. Grade 5 adverse events were reported regardless of attribution to study treatment. (NCT00006903)
Timeframe: During study treatment and up to 30 days after stopping study

Intervention	Participants (Count of Participants)
	Anemia	Fatigue	Gastrointestinal	Nausea	Vomiting	Diarrhea	Anorexia	Metabolic	Neurologic	Depression	Pain	Dyspnea	Thrombosis/embolism, regardless of attribution
Grade 3 (CTCAE v 3.0)	1	1	1	3	1	1	2	2	2	1	1	1	0
Grade 4 (CTCAE v 3.0)	1	0	0	0	0	0	0	0	0	0	0	0	3
Grade 5	0	0	0	0	0	0	0	0	0	0	0	0	1

Clinical Benefit Defined as Complete Response (CR), Partial Response (PR) or Stable Disease (SD) Lasting >= 24 Weeks, as Determined by the Investigator According to RECIST v1.1

Clinical Benefit was defined as CR, PR, or SD lasting more than equal to 24 weeks from randomization in participants with measurable disease at baseline, as determined by the investigator according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1. Per RECIST v1.1 for target lesions assessed by CT or MRI: CR, Disappearance of all target lesions; PR, PR >= 30% decrease in the sum of diameters of target lesions (TL) taking as reference the baseline sum of diameters; SD, neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Disease Progression (PD), PD>= 20% increase in the sum of diameters of TL taking as reference the smallest sum on study(Nadir). In addition to the relative increase of 20% sum must have demonstrate an absolute increase of at least 5mm. (NCT03584009)
Timeframe: Randomization through till 6 months after the last participant is enrolled into the study (up to approximately 23 months)

Intervention	Percentage of Participants (Number)
Venetoclax + Fulvestrant	11.8
Fulvestrant	13.7

Duration of Response (DOR)

DOR was defined as the time from the first occurrence of a documented objective response to the time of the first documented disease progression (as determined by the investigator according to RECIST v1.1) or death from any cause, whichever occurs first. (NCT03584009)
Timeframe: Time from first occurrence of a documented objective response to the first documented disease progression or death from any cause, whichever occurs first, until 6 months after the last participant is enrolled in the study (up to approximately 23 months)

Intervention	Months (Median)
Venetoclax + Fulvestrant	NA
Fulvestrant	3.61

Objective Response (OR)

OR was defined as CR or PR, in participants with measurable disease at baseline as determined by the investigator according to RECIST v1.1. (NCT03584009)
Timeframe: Randomization through till 6 months after the last participant is enrolled into the study (up to approximately 23 months)

Intervention	Percentage of Participants (Number)
Venetoclax + Fulvestrant	3.9
Fulvestrant	5.9

Overall Survival (OS)

OS was defined as the time from randomization to death due to any cause. (NCT03584009)
Timeframe: Randomization to death from any cause, through till the end of the study (up to approximately 32 months)

Intervention	Months (Median)
Venetoclax + Fulvestrant	19.71
Fulvestrant	NA

Percentage of Participants With Adverse Events (AEs)

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study were also considered as AEs. (NCT03584009)
Timeframe: Baseline up until 28 days after the last dose of study drug (venetoclax or fulvestrant, whichever is later) up to approximately 32 months

Intervention	Percentage of Participants (Number)
Venetoclax + Fulvestrant	94.0
Fulvestrant	76.5

Progression Free Survival (PFS)

PFS was defined as the time from randomization to the first occurrence of disease progression (as determined by the investigator according to RECIST v1.1) or death from any cause, whichever occurs first. (NCT03584009)
Timeframe: Randomization through till 6 months after the last participant is enrolled into the study (up to approximately 23 months)

Intervention	Months (Median)
Venetoclax + Fulvestrant	2.69
Fulvestrant	1.94

Plasma Concentrations of Fulvestrant (in Absence of Venetoclax)

(NCT03584009)
Timeframe: Cycle 2 Day 1: pre-dose (within 1 hr); any time during visits up to study drug discontinuation/Early Termination (up to approximately 32 months)

Intervention	μg/mL (Geometric Mean)
	Cycle 2 Day 1: pre-dose	Treatment discontinuation visit
Fulvestrant	0.0103	0.0139

Plasma Concentrations of Fulvestrant (in Presence of Venetoclax)

(NCT03584009)
Timeframe: Cycle 2 Day 1: pre-dose (within 1 hr); Cycle 6 Day 1: pre-dose (within 1 hr); any time during visits up to study drug discontinuation/Early Termination (up to approximately 32 months)

Intervention	μg/mL (Geometric Mean)
	Cycle 2 Day 1: pre-dose	Cycle 6 Day 1: pre-dose	Treatment discontinuation visit
Fulvestrant	0.0129	0.0145	0.00985

Plasma Concentrations of Venetoclax

(NCT03584009)
Timeframe: Cycle 1 Day 1: 4 hours (hrs) post-dose; Cycle 2 Day 1: pre-dose (within 1 hr) and 2, 4, 6, 8 hrs post-dose; any time during visits up to study drug discontinuation/Early Termination (up to approximately 32 months)

Intervention	Micrograms per Milliliters (μg/mL) (Geometric Mean)
	Cycle 1 Day 1: 4 hrs post-dose	Cycle 2 Day 1: pre-dose	Cycle 2 Day 1: 2 hrs post-dose	Cycle 2 Day 1: 4 hrs post-dose	Cycle 2 Day 1: 6 hrs post-dose	Cycle 2 Day 1: 8 hrs post-dose	Treatment discontinuation visit
Venetoclax	1.78	1.04	1.45	2.51	3.32	3.55	0.0112

Phase 1b Dose Escalation: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) Through Day 28 at Each Dose Level of GS-5829

"A DLT was a toxicity as defined below:~Grade ≥ 4 neutropenia~Grade ≥ 3 neutropenia with fever~Grade ≥ 3 thrombocytopenia~Grade ≥ 2 bleeding (e.g., gastrointestinal, respiratory, epistaxis, purpura)~Grade ≥ 3 or higher non-hematologic toxicity, except:~Grade 3 nausea or emesis with maximum duration of 48 hours on adequate medical therapy~Grade 3 diarrhea which persists for < 72 hours in the absence of adequate medical therapy~Grade ≥ 2 non-hematologic treatment-emergent adverse event (TEAE) that in the opinion of the investigator is of potential clinical significance such that further dose escalation would expose participants to unacceptable risk~Treatment interruption of ≥ 7 days due to unresolved toxicity~Grade 3 or Grade 4 elevation in aspartate transaminase (AST) or alanine transaminase (ALT) associated with a Grade 2 elevation in bilirubin that is at least possibly related to study drug" (NCT02983604)
Timeframe: Baseline up to 28 days

Intervention	Participants (Count of Participants)
GS-5829 4 mg + Exemestane	1
GS-5829 4 mg + Fulvestrant	0
GS-5829 6 mg + Fulvestrant	0
GS-5829 9 mg + Fulvestrant	0

Phase 1b Dose Escalation: PK Parameter: AUCtau of GS-5829

AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). (NCT02983604)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Day 15

Intervention	h*ng/mL (Mean)
GS-5829 4 mg + Exemestane	4989.809
GS-5829 4 mg + Fulvestrant	5218.820
GS-5829 6 mg + Fulvestrant	3937.709
GS-5829 9 mg + Fulvestrant	7638.847

Phase 1b Dose Escalation: Pharmacokinetic (PK) Parameter: Cmax of GS-5829

Cmax is defined as the maximum observed concentration of drug. (NCT02983604)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Days 1 and 15

,,,

Intervention	ng/mL (Mean)
	Day 1	Day 15
GS-5829 4 mg + Exemestane	318.25	389.666
GS-5829 4 mg + Fulvestrant	247.00	370.333
GS-5829 6 mg + Fulvestrant	244.00	375.666
GS-5829 9 mg + Fulvestrant	518.00	634.000

Phase I: Disease Control Rate (DCR)

DCR is defined as the percentage of participants in the population with a confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) lasting >=6 months, as assessed by the investigator per RECIST v1.1 criteria. (NCT02964507)
Timeframe: Up to 3 year and 8 months

Intervention	Percentage of participants (Number)
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	36
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	0
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	17
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	14
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	28
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	9

Phase I: Duration of Response (DoR)

DoR is defined as the time (in months) from date of first documented evidence of confirmed CR or PR to the date of first documented PD, as assessed by the investigator per RECIST v1.1 criteria, or to the date of death due to any cause among participants with a Best overall response (BOR) of confirmed CR or PR. (NCT02964507)
Timeframe: Up to 3 year and 8 months

Intervention	Months (Median)
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	13.1
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	5.8
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	14.0
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	4.3

Phase I: Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment

Number of participants who withdrew due to toxicity and changes in safety assessment including laboratory parameters and vital signs have been presented. (NCT02964507)
Timeframe: Up to 4 year and 4 months

Intervention	Participants (Count of Participants)
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	6
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	0
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	6
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	2
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	1
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	2

Phase I: Number of Participants With Dose Limiting Toxicities (DLTs)

An event was considered DLT if it occurred within first 28 days of treatment and met one of following DLT criteria: Grade3 or greater neutropenia for >=5 days, febrile neutropenia, Grade4 anemia of any duration, Grade4 thrombocytopenia of any duration or Grade3 thrombocytopenia with bleeding, alanine aminotransferase (ALT) >3 times (x) upper limit of normal (ULN)+bilirubin >=2x ULN (>35 % direct) or ALT between 3-5xULN with bilirubin <2xULN but with hepatitis symptoms or rash, Grade3 nausea,vomiting or diarrhea that did not improve within 72hour despite appropriate supportive treatment(s), Grade4 nausea,vomiting,or diarrhea, Grade3 hypertension (uncontrolled despite addition of upto 2 antihypertensive medications), Grade4 hypertension, other Grade3 or greater clinically significant non-hematologic toxicity (including QT duration corrected for heart rate by Fridericia's formula (QTcF), ejection fraction 10% from Baseline. (NCT02964507)
Timeframe: Up to 28 days

Intervention	Participants (Count of Participants)
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	2
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	0
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	1
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	1
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	0
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	2

Phase I: Objective Response Rate-Investigator Assessment

Objective Response Rate is defined as the percentage of participants who demonstrate a Best Response of confirmed complete response (CR) or partial response (PR), as assessed by the investigator per response evaluation criteria in solid tumors (RECIST) version (v) 1.1 criteria. (NCT02964507)
Timeframe: Up to 3 year and 8 months

Intervention	Percentage of participants (Number)
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	21
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	0
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	12
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	0
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	17
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	9

Phase I: Progression-free Survival (PFS)

PFS is defined as the time (in months) from the date of first dose until the date of first documented PD, as assessed by the investigator per RECIST v1.1 criteria, or date of death due to any cause, whichever occurs first. PD is defined as at least a 20% increase in the sum of the diameters of target lesions taking as a reference the smallest sum of diameters for this study. (NCT02964507)
Timeframe: Up to 3 year and 8 months

Intervention	Months (Median)
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	5.6
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	1.7
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	2.1
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	7.2
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	4.0
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	1.8

Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays Until End of the Study

Number of participants with dose reductions and dose interruption or delay due to any reason is presented. Number of participants with dose reductions and dose interruption or delay due to any reason from start of the treatment until end of the study were reported. (NCT02964507)
Timeframe: Up to 4 year and 4 months

,,,,,

Intervention	Participants (Count of Participants)
	Dose reduction	Dose interruption/delay
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	14	23
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	9	23
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	3	9
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	3	4
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	8	9
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	7	15

Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays

Number of participants with dose reductions and dose interruption or delay due to any reason is presented. (NCT02964507)
Timeframe: Up to 3 year and 8 months

,,,,,

Intervention	Participants (Count of Participants)
	Dose reduction	Dose interruption/delay
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	14	23
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	3	9
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	3	4
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	8	9
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	7	15
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	9	23

Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, any other situation such as important medical events according to medical or scientific judgement or is associated with liver injury and impaired liver function. Any other adverse event apart from SAE is considered as non-SAE. Number of participants with non-serious AEs and SAEs collected from start of the treatment until end of the study were reported. (NCT02964507)
Timeframe: Up to 4 year and 4 months

,,,,,

Intervention	Participants (Count of Participants)
	Non-serious AEs	SAEs
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	33	5
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	42	10
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	12	1
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	7	3
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	11	2
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	18	6

Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)

,,,,,

Intervention	Participants (Count of Participants)
	Non-serious AEs	SAEs
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	33	5
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	42	10
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	12	1
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	7	3
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	11	2
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	18	6

Phase I: Plasma Concentration of Fulvestrant

Blood samples were collected at indicated time points for PK analysis of Fulvestrant. (NCT02964507)
Timeframe: Day 1: Pre-dose on Weeks 1, 3, 5, 9, 17, 25

,,,,,

Intervention	Nanograms per milliliter (Mean)
	Week 1 Day 1, Pre-dose, n=30,11,40,6,17,11	Week 3 Day 1, Pre-dose, n=30,11,32,7,16,10	Week 5 Day 1, Pre-dose, n=25,9,31,5,16,10	Week 9 Day 1, Pre-dose, n=19,3,19,1,10,5	Week 17 Day 1, Pre-dose, n=15,2,6,1,6,3	Week 25 Day 1, Pre-dose, n=10,1,4,1,4,1
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	NA	13.32481	19.82642	16.33764	16.70103	18.07473
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	NA	12.44415	16.51574	13.98242	13.62853	18.60548
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	NA	9.42742	14.72467	13.05750	20.63475	14.21220
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	NA	11.34839	15.35394	20.43840	12.59940	19.05100
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	NA	10.25047	13.83940	11.84244	16.33830	12.24970
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	NA	12.41568	16.87293	11.10370	12.81337	16.05110

Phase I: Plasma Concentration of GSK3529246

Blood samples were collected at indicated time points for PK analysis of GSK3529246. GSK3529246 is an active metabolite of GSK525762. (NCT02964507)
Timeframe: Day 1: Pre-dose, 0.5, 1, 3 hours on Weeks 1 and 3; Day 1: Pre-dose, 0.5-1, 4-8 hours on Week 5, Day 1: pre-dose, 0.5-1 hour on Weeks 9, 17, 25

Intervention	Nanograms per milliliter (Mean)
	Week 1 Day 1, Pre-dose, n=30,11,41,7,17,11	Week 1 Day 1, 0.5 hour, n=31,11,39, 7,17,10	Week 1 Day 1, 1 hour, n=31,11,41,7,18,10	Week 1 Day 1, 3 hours, n=31,11,39,6,17,10	Week 3 Day 1, Pre-dose, n=29,12,31,5,16,8	Week 3 Day 1, 0.5 hour, n=28,11,30,4,13,7	Week 3 Day 1, 1 hour, n=28,11,30,5,13,7	Week 3 Day 1, 3 hours, n=28,10,29,5,13,7	Week 5 Day 1, Pre-dose, n=26,9,34,5,14,10	Week 5 Day 1, 0.5-1 hour, n=24,7,26,3,11,7	Week 5 Day 1, 4-8 hours, n=6,1,9,1,5,0	Week 9 Day 1, Pre-dose, n=17,2,23,2,10,4	Week 9 Day 1, 0.5-1 hour, n=13,1,17,2,6,3	Week 17 Day 1, Pre-dose, n=11,2,8,2,6,3	Week 17 Day 1, 0.5-1 hour, n=9,2,9,2,4,1	Week 25 Day 1, Pre-dose, n=9,1,5,2,4,1
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	NA	126.818	205.364	216.364	58.708	243.736	294.573	341.500	41.600	237.614	208.000	33.850	36.000	21.450	71.800	30.100

Phase I: Plasma Concentration of GSK3529246

Intervention	Nanograms per milliliter (Mean)
	Week 1 Day 1, Pre-dose, n=30,11,41,7,17,11	Week 1 Day 1, 0.5 hour, n=31,11,39, 7,17,10	Week 1 Day 1, 1 hour, n=31,11,41,7,18,10	Week 1 Day 1, 3 hours, n=31,11,39,6,17,10	Week 3 Day 1, Pre-dose, n=29,12,31,5,16,8	Week 3 Day 1, 0.5 hour, n=28,11,30,4,13,7	Week 3 Day 1, 1 hour, n=28,11,30,5,13,7	Week 3 Day 1, 3 hours, n=28,10,29,5,13,7	Week 5 Day 1, Pre-dose, n=26,9,34,5,14,10	Week 5 Day 1, 0.5-1 hour, n=24,7,26,3,11,7	Week 9 Day 1, Pre-dose, n=17,2,23,2,10,4	Week 9 Day 1, 0.5-1 hour, n=13,1,17,2,6,3	Week 17 Day 1, Pre-dose, n=11,2,8,2,6,3	Week 17 Day 1, 0.5-1 hour, n=9,2,9,2,4,1	Week 25 Day 1, Pre-dose, n=9,1,5,2,4,1	Week 25 Day 1, 0.5-1 hour, n=5,0,6,2,2,1
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	NA	186.970	299.100	300.000	49.230	288.671	441.571	403.571	54.231	203.486	69.625	161.367	84.600	301.000	NA	76.300

Phase I: Plasma Concentration of GSK3529246

,,,

Intervention	Nanograms per milliliter (Mean)
	Week 1 Day 1, Pre-dose, n=30,11,41,7,17,11	Week 1 Day 1, 0.5 hour, n=31,11,39, 7,17,10	Week 1 Day 1, 1 hour, n=31,11,41,7,18,10	Week 1 Day 1, 3 hours, n=31,11,39,6,17,10	Week 3 Day 1, Pre-dose, n=29,12,31,5,16,8	Week 3 Day 1, 0.5 hour, n=28,11,30,4,13,7	Week 3 Day 1, 1 hour, n=28,11,30,5,13,7	Week 3 Day 1, 3 hours, n=28,10,29,5,13,7	Week 5 Day 1, Pre-dose, n=26,9,34,5,14,10	Week 5 Day 1, 0.5-1 hour, n=24,7,26,3,11,7	Week 5 Day 1, 4-8 hours, n=6,1,9,1,5,0	Week 9 Day 1, Pre-dose, n=17,2,23,2,10,4	Week 9 Day 1, 0.5-1 hour, n=13,1,17,2,6,3	Week 17 Day 1, Pre-dose, n=11,2,8,2,6,3	Week 17 Day 1, 0.5-1 hour, n=9,2,9,2,4,1	Week 25 Day 1, Pre-dose, n=9,1,5,2,4,1	Week 25 Day 1, 0.5-1 hour, n=5,0,6,2,2,1
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	NA	174.474	249.793	276.516	37.972	290.482	414.143	369.821	37.480	270.979	263.833	31.041	244.162	41.445	189.422	65.756	203.160
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	NA	115.419	175.197	243.517	121.820	192.275	271.200	252.000	36.620	170.800	292.000	22.700	228.000	72.450	129.050	64.500	204.950
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	NA	135.012	228.597	262.044	42.213	195.037	323.767	321.404	56.659	211.846	322.778	39.323	178.914	21.214	183.671	49.700	220.367
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	NA	202.224	327.072	365.059	48.013	256.669	511.692	438.692	52.243	295.518	382.400	58.890	283.667	44.483	322.500	20.508	121.300

Phase I: Plasma Concentration of GSK525762

Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK525762. (NCT02964507)
Timeframe: Day 1: Pre-dose, 0.5, 1, 3 hours on Weeks 1 and 3; Day 1: Pre-dose, 0.5-1, 4-8 hours on Week 5; Day 1: Pre-dose, 0.5-1 hour on Weeks 9, 17, 25

Intervention	Nanograms per milliliter (Mean)
	Week 1 Day 1, Pre-dose, n=30,11,41,7,17,11	Week 1 Day 1, 0.5 hour, n=31,11,40,7,17,10	Week 1 Day 1, 1 hour, n=31,10,40,7,18,10	Week 1 Day 1, 3 hours, n=31,10,39,6,17,10	Week 3 Day 1, Pre-dose, n=29,12,31,5,16,8	Week 3 Day 1, 0.5 hour, n=28,11,29,4,13,7	Week 3 Day 1, 1 hour, n=28,11,30,5,13,7	Week 3 Day 1, 3 hours, n=28,10,29,5,13,7	Week 5 Day 1, Pre-dose, n=26,9,34,5,14,10	Week 5 Day 1, 0.5-1 hour, n=24,7,26,3,11,7	Week 5 Day 1, 4-8 hours, n=6,1,9,1,5,0	Week 9 Day 1, Pre-dose, n=17,2,23,2,10,4	Week 9 Day 1, 0.5-1 hour, n=13,1,17,2,6,3	Week 17 Day 1, Pre-dose, n=11,2,8,2,6,3	Week 17 Day 1, 0.5-1 hour, n=9,2,9,2,4,1	Week 25 Day 1, Pre-dose, n=9,1,5,2,4,1
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+AI Failure <12M)	NA	814.364	828.800	526.400	15.797	680.936	576.427	447.700	15.251	463.854	145.000	5.055	69.400	1.365	32.100	NA

Phase I: Plasma Concentration of GSK525762

Intervention	Nanograms per milliliter (Mean)
	Week 1 Day 1, Pre-dose, n=30,11,41,7,17,11	Week 1 Day 1, 0.5 hour, n=31,11,40,7,17,10	Week 1 Day 1, 1 hour, n=31,10,40,7,18,10	Week 1 Day 1, 3 hours, n=31,10,39,6,17,10	Week 3 Day 1, Pre-dose, n=29,12,31,5,16,8	Week 3 Day 1, 0.5 hour, n=28,11,29,4,13,7	Week 3 Day 1, 1 hour, n=28,11,30,5,13,7	Week 3 Day 1, 3 hours, n=28,10,29,5,13,7	Week 5 Day 1, Pre-dose, n=26,9,34,5,14,10	Week 5 Day 1, 0.5-1 hour, n=24,7,26,3,11,7	Week 9 Day 1, Pre-dose, n=17,2,23,2,10,4	Week 9 Day 1, 0.5-1 hour, n=13,1,17,2,6,3	Week 17 Day 1, Pre-dose, n=11,2,8,2,6,3	Week 17 Day 1, 0.5-1 hour, n=9,2,9,2,4,1	Week 25 Day 1, Pre-dose, n=9,1,5,2,4,1	Week 25 Day 1, 0.5-1 hour, n=5,0,6,2,2,1
Phase I-GSK525762 80 mg + FUL 500 mg (CDK4/6+AI Failure)	NA	1155.300	1069.400	782.600	6.799	917.714	895.286	523.714	77.465	457.229	6.640	309.627	7.270	214.000	NA	186.000

Phase I: Plasma Concentration of GSK525762

,,,

Intervention	Nanograms per milliliter (Mean)
	Week 1 Day 1, Pre-dose, n=30,11,41,7,17,11	Week 1 Day 1, 0.5 hour, n=31,11,40,7,17,10	Week 1 Day 1, 1 hour, n=31,10,40,7,18,10	Week 1 Day 1, 3 hours, n=31,10,39,6,17,10	Week 3 Day 1, Pre-dose, n=29,12,31,5,16,8	Week 3 Day 1, 0.5 hour, n=28,11,29,4,13,7	Week 3 Day 1, 1 hour, n=28,11,30,5,13,7	Week 3 Day 1, 3 hours, n=28,10,29,5,13,7	Week 5 Day 1, Pre-dose, n=26,9,34,5,14,10	Week 5 Day 1, 0.5-1 hour, n=24,7,26,3,11,7	Week 5 Day 1, 4-8 hours, n=6,1,9,1,5,0	Week 9 Day 1, Pre-dose, n=17,2,23,2,10,4	Week 9 Day 1, 0.5-1 hour, n=13,1,17,2,6,3	Week 17 Day 1, Pre-dose, n=11,2,8,2,6,3	Week 17 Day 1, 0.5-1 hour, n=9,2,9,2,4,1	Week 25 Day 1, Pre-dose, n=9,1,5,2,4,1	Week 25 Day 1, 0.5-1 hour, n=5,0,6,2,2,1
Phase I-GSK525762 60 mg+FUL 500 mg (AI Failure)	NA	895.466	855.734	637.097	7.046	766.179	737.536	423.500	5.804	640.700	306.900	7.257	607.408	9.401	372.778	34.847	418.000
Phase I-GSK525762 60 mg+FUL 500 mg (CDK4/6+ AI Failure >= 12M)	NA	824.081	947.343	717.769	8.598	504.516	581.073	369.179	66.527	555.237	303.000	9.000	445.291	3.591	521.241	10.198	380.483
Phase I-GSK525762 60+FUL500mg CDK4/6+AI Failure>=12M Bone Only Disease	NA	646.251	634.300	732.833	150.410	730.250	596.800	422.800	15.814	705.667	431.000	3.265	817.000	16.850	270.000	10.740	251.350
Phase I-GSK525762 80mg + FUL 500 mg (AI Failure)	NA	969.265	1061.722	831.176	11.371	808.846	875.077	471.154	14.603	685.773	352.400	16.469	621.867	7.217	640.000	1.560	314.000

Duration of Clinical Benefit (DoCB)

Median time from randomisation until objective progression or death (in the absence of objective progression), measured only in those patients who are clinical benefit responders (NCT00256698)
Timeframe: RECIST tumour assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009

Intervention	months (Median)
Fulvestrant + Anastrozole	18.5
Anastrozole	18.1

Duration of Response (DoR)

Median time from randomisation until objective progression or death (in the absence of objective progression), measured only in those patients who are objective responders (NCT00256698)
Timeframe: RECIST tumour assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009

Intervention	months (Median)
Fulvestrant + Anastrozole	22.3
Anastrozole	18.2

Overall Survival (OS)

Overall survival is equivalent to time to death. Time from randomisation until the date of death (NCT00256698)
Timeframe: All deaths occurring between randomisation and data cut-off on 30th April 2009 are included.

Intervention	months (Median)
Fulvestrant + Anastrozole	37.8
Anastrozole	38.2

Percentage of Clinical Benefit Rate (CBR) Responders

No. of patients who were clinical benefit responders over the no. of randomised patients x100. A clinical benefit responder = a patient whose best response is CR, PR or SD>=24 weeks (where a best response of SD = no new lesions and for existing lesions; neither suffient shrinkage to count as PR nor sufficient growth to count as progression) (NCT00256698)
Timeframe: RECIST tumour assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009

Intervention	Percentage of participants (Number)
Fulvestrant + Anastrozole	55.0
Anastrozole	55.1

Percentage of Evaluable Participants With Objective Response Rate (ORR)

No. of patients who were objective responders over the no. of patients evaluable for response x100. An objective responder = a patient whose best response is either CR (disappearance of all lesions) or PR (>= 30% shrinkage in the sum of the longest diamemeters of the measurable lesions + no new lesions + no progression of non-measurable lesions) (NCT00256698)
Timeframe: RECIST tumour assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009

Intervention	Percentage of evaluable participants (Number)
Fulvestrant + Anastrozole	31.8
Anastrozole	33.6

Time to Progression (TTP)

"RECIST (Response Evaluation Criteria in Solid Tumours) assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009. TTP, time in months to worsen 'progression' according to RECIST criteria. (RECIST is a set of published rules that define when cancer patients improve respond, stay the same stableor worsen progression during treatments." (NCT00256698)
Timeframe: RECIST assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009

Intervention	months (Median)
Fulvestrant + Anastrozole	10.8
Anastrozole	10.2

Time to Treatment Failure (TTF)

Time from randomisation until the date of discontinuation of randomised treatment for any reason (NCT00256698)
Timeframe: From randomisation until data cut-off on 30th April 2009

Intervention	months (Median)
Fulvestrant + Anastrozole	12.4
Anastrozole	11.4

Objective Tumor Response Rate for Participants With HER2-negative Tumors

Response was defined by the RECIST. A responding participant had either a Complete Response (disappearance of all target lesions) or Partial Response (30% decrease in sum of longest diameter of target lesions). The response rate of measurable tumors will be estimated with its 95% confidence interval according to treatment arm. (NCT00390455)
Timeframe: Up to 5 years

Intervention	percentage of participants (Number)
Arm I (Lapatinib)	13
Arm II (Placebo)	23

Objective Tumor Response Rate for Participants With HER2-positive Tumors

Intervention	percentage of participants (Number)
Arm I (Lapatinib)	38
Arm II (Placebo)	17

Objective Tumor Response Rate

Response was defined by the Response Evaluation Criteria in Solid Tumors (RECIST). A responding participant had either a Complete Response (disappearance of all target lesions) or Partial Response (30% decrease in sum of longest diameter of target lesions). The response rate of measurable tumors will be estimated with its 95% confidence interval according to treatment arm. (NCT00390455)
Timeframe: Up to 5 years

Intervention	percentage of participants (Number)
Arm I (Lapatinib)	20
Arm II (Placebo)	9

Overall Survival (OS)

Overall survival was measured as the interval from study entry until death, from any cause, or last contact. (NCT00390455)
Timeframe: Study entry to death or last follow-up, up to 5 years

Intervention	months (Median)
Arm I (Lapatinib)	29.9
Arm II (Placebo)	26.4

Progression-free Survival (PFS)

PFS was defined as the interval from study entry until disease progression or death resulting from any cause, which ever occurred first. Progression is defined as a 20% increase in the sum of longest diameter of target lesions (per RECIST criteria). (NCT00390455)
Timeframe: Interval from randomization until disease progression or death, whichever occurs first, assessed up to 5 years

Intervention	months (Median)
Arm I (Lapatinib)	4.7
Arm II (Placebo)	3.8

Progression-free Survival for Participants With HER2-negative Tumors

PFS was defined as the interval from study entry until disease progression or death resulting from any cause, which ever occurred first. (NCT00390455)
Timeframe: Up to 5 years

Intervention	months (Median)
Arm I (Lapatinib)	4.1
Arm II (Placebo)	3.8

Progression-free Survival for Participants With HER2-positive Tumors

PFS was defined as the interval from study entry until disease progression or death resulting from any cause, whichever occurred first. (NCT00390455)
Timeframe: Up to 5 years

Intervention	months (Median)
Arm I (Lapatinib)	5.9
Arm II (Placebo)	3.3

Clinical Benefit (CR, PR, Confirmed or Unconfirmed, or Stable Disease >= 24 Weeks).

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable, Does not qualify for CR, PR, Progression or Symptomatic Deterioration. Clinical Benefit = CR + PR + Stable >= 24 weeks (NCT00075764)
Timeframe: Every 4 weeks while on treatment. Then every 3 months until progression, then six months for two years then annually until four years or until death, which ever occurs first.

Intervention	percentage of participants (Number)
Arm I Anastrozole	70
Arm II Anastrozole and Fulvestrant	73

Overall Survival

From date of randomization to date of death due to any cause. Patients last known to be alive are censored at last date of contact. (NCT00075764)
Timeframe: Every 4 weeks while on treatment. Then every 3 months until progression, then six months for two years then annually until four years or until death, which ever occurs first.

Intervention	months (Median)
Arm I Anastrozole	41.3
Arm II Anastrozole and Fulvestrant	47.7

Time to Tumor Progression

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target measurable lesions over the smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. Unequivocal progression of non-measurable disease in the opinion of the treating physician. Appearance of any new lesion/site. Death due to disease without prior documentation of progression and without symptomatic deterioration. From date of randomization to time of first documentation of progression, symptomatic deterioration or death due to any cause. Patients last known to be alive and progression free are considered at last date of contact. (NCT00075764)
Timeframe: Every 4 weeks while on treatment. Then every 3 months until progression, then six months for two years then annually until four years or until death, which ever occurs first.

Intervention	months (Median)
Arm I Anastrozole	13.5
Arm II Anastrozole and Fulvestrant	15.0

Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs

Adverse Events (AEs) are reported by CTCAE version 3.0 terminology. For each patient, worst grade of each event type is reported. Grade3 (Severe), Grade4 (Life-threatening), Grade 5 (Fatal) (NCT00075764)
Timeframe: Patients were assessed for adverse events after each cycle (1 cycle = 28 days) while on treatment.

Intervention	Participants (Number)
	ALT, SGPT (serum glutamic pyruvic transaminase)	AST, SGOT	Albumin, serum-low (hypoalbuminemia)	Alkaline phosphatase	Anorexia	Bilirubin (hyperbilirubinemia)	CNS cerebrovascular ischemia	Calcium, serum-high (hypercalcemia)	Cataract	Confusion	Constipation	Dehydration	Diarrhea	Dizziness	Dyspnea (shortness of breath)	Edema: limb	Fatigue (asthenia, lethargy, malaise)	Febrile neutropenia	Fracture	Glucose, serum-high (hyperglycemia)	Hemoglobin	Hemolysis	Hot flashes/flushes	Hypertension	Inf w/normal ANC or Gr 1-2 neutrophils - Blood	Inf w/normal ANC or Gr 1-2 neutrophils - UTI	Infection with unknown ANC - Urinary tract NOS	Insomnia	Joint-effusion	Leukocytes (total WBC)	Lymphopenia	Memory impairment	Mood alteration - agitation	Mood alteration - anxiety	Mood alteration - depression	Mucositis/stomatitis (functional/symp) - Pharynx	Muscle weakness, not d/t neuropathy - body/general	Nausea	Neurology-Other (Specify)	Neuropathy: sensory	Neutrophils/granulocytes (ANC/AGC)	Pain - Abdomen NOS	Pain - Back	Pain - Bone	Pain - Breast	Pain - Buttock	Pain - Chest wall	Pain - Chest/thorax NOS	Pain - Extremity-limb	Pain - Head/headache	Pain - Joint	Pain - Muscle	Pain - Neck	Pain - Pelvis	Pain-Other (Specify)	Platelets	Rash/desquamation	Sodium, serum-low (hyponatremia)	Speech impairment (e.g., dysphasia or aphasia)	Sudden death	Syncope (fainting)	Thrombosis/embolism (vascular access-related)	Thrombosis/thrombus/embolism	Tinnitus	Tumor flare	Urticaria (hives, welts, wheals)	Vomiting	Weight gain
Arm I Anastrozole	1	3	1	1	0	1	0	1	1	0	1	1	2	1	1	1	7	1	1	1	1	1	2	2	1	1	0	0	0	0	3	1	0	1	0	1	1	3	1	1	0	1	5	1	1	1	0	1	0	1	5	3	0	0	2	2	1	0	1	0	0	3	6	0	0	0	3	0
Arm II Anastrozole and Fulvestrant	1	1	1	0	1	0	2	0	1	1	1	1	1	2	1	1	9	0	2	2	3	1	7	1	0	1	2	1	2	1	3	0	1	0	3	0	0	1	0	0	2	2	7	1	0	0	1	1	3	0	7	0	1	3	1	2	1	1	0	1	1	1	7	1	2	1	2	1

Breast Cancer Specific Survival (BCsS) Events

"BCsS events has been evaluated in patients treated with Fulvestrant for 3 years and Anastrozole for 5 years as compared to BCsS in patients treated with anastrozole for 5 years.~BCsS event is defined as the death from breast cancer." (NCT00543127)
Timeframe: Up to 5 years

Intervention	Participants (Count of Participants)
Fulvestrant + Anastrozole	17
Anastrozole	18

Disease Free Survival (DFS) Events

"Disease-free survival (DFS) has been evaluated in patients treated with Fulvestrant for 3 years and Anastrozole for 5 years as compared to DFS in patients treated with anastrozole for 5 years.~DFS event is defined as the evidence of local and/or distant recurrence, new primary breast tumour, or death from any cause." (NCT00543127)
Timeframe: Up to 5 years

Intervention	Participants (Count of Participants)
Fulvestrant + Anastrozole	49
Anastrozole	62

Overall Survival (OS) Event

"OS event has been evaluated in patients treated with Fulvestrant for 3 years and Anastrozole for 5 years as compared to DFS in patients treated with anastrozole for 5 years.~OS event is defined as the death from any cause." (NCT00543127)
Timeframe: Up to 5 years

Intervention	Participants (Count of Participants)
Fulvestrant + Anastrozole	28
Anastrozole	34

Time to Recurrence (TR) Event

"TR event has been evaluated in patients treated with Fulvestrant for 3 years and Anastrozole for 5 years as compared to DFS in patients treated with anastrozole for 5 years.~TR event is defined as the evidence of breast cancer recurrence (local and/or distant recurrence of breast cancer, does not include second primary malignancies or deaths from any cause)." (NCT00543127)
Timeframe: Up to 5 years

Intervention	Participants (Count of Participants)
Fulvestrant + Anastrozole	36
Anastrozole	46

Median Change in Percent Positive Cells From Baseline of Ki-67

Median change in percent positive cells of Ki-67 from baseline will be reported with IQR (NCT02384239)
Timeframe: Up to 24 months

Intervention	change in percent positive cells (Median)
Palbociclib 100mg	-8
Palbociclib 125mg	-6

Median Change in Percent Positive Cells From Baseline of pS780-Rb

Median change in percent positive cells of pS780-Rb from baseline will be reported with IQR (NCT02384239)
Timeframe: Up to 24 months

Intervention	change in percent positive cells (Median)
Palbociclib 100mg	-3
Palbociclib 125mg	-6

Median Change in Percent Positive Cells From Baseline of Total-Rb

Median change in percent positive cells of Total-Rb from baseline will be reported with interquartile range (IQR) (NCT02384239)
Timeframe: Up to 24 months

Intervention	change in percent positive cells (Median)
Palbociclib 100mg	4
Palbociclib 125mg	5

Percentage of Participants With Grade 3 or 4 Neutropenia

Grade 3/4 neutropenia as defined by NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.03 in patients with prior exposure to 1-3 lines of chemotherapy for metastatic breast cancer (NCT02384239)
Timeframe: Up to 24 months

Intervention	percentage of participants (Number)
Palbociclib 100mg	19.4
Palbociclib 125mg	20.5

Progression-free Survival (PFS)

PFS defined as the interval from study entry to the first documented evidence of disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as at least a 20% increase in the sum of the longest diameter (SLD) of target lesions, taking as reference the smallest sum SLD recorded since the treatment started and minimum 5 mm increase over the nadir, or the appearance of one or more new lesions. Patients who remain progression-free at the time of analysis will be censored at their last date of follow-up. (NCT02384239)
Timeframe: Up to 24 months

Intervention	months (Median)
Palbociclib 100mg	6.53
Palbociclib 125mg	9.4

Proportion of Participants With an Objective Response

Defined as the proportion of patients whose best overall response, according to RECIST, is either complete response (CR), a partial response (PR) at 24 weeks. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response. (NCT02384239)
Timeframe: 24 weeks

Intervention	proportion of participants (Number)
Palbociclib 100mg	0.1111
Palbociclib 125mg	0.0625

Proportion of Participants With Demonstrated Clinical Benefit

Defined as the proportion of patients whose best overall response, according to RECIST, is either complete response (CR), a partial response (PR) or stable disease (SD) at 24 weeks. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response. (NCT02384239)
Timeframe: 24 weeks

Intervention	proportion of participants (Number)
Palbociclib 100mg	0.67
Palbociclib 125mg	0.75

Percentage of Grade 3-5 Adverse Events

To evaluate the safety and tolerability of administering Abemaciclib and Fulvestrant. Toxicity and adverse events are based on the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0. (NCT04305236)
Timeframe: From start of study treatment to surgery, on average we expect 6 months.

Intervention	percentage of participants (Number)
Abemaciclib and Fulvestrant	0

Adverse Events Leading to Dose Reduction of AZD2014

(NCT01597388)
Timeframe: Up to 28 Days

Intervention	Participants (Number)
35 mg BID Continuous	1
50 mg BID Continuous	7
75 mg QD Continuous	4
100 mg QD Continuous	6
125 mg BID Intermittent Days 1 and 2 (Fasted)	12
125 mg BID Intermittent Days 1 and 2 (Fed)	0
170 mg BID Intermittent Days 1 and 2 (Fasted)	4
170 mg BID Intermittent Days 1 and 2 (Fed)	3
125 mg BID Intermittent Days 1 and 4 (Fasted)	2

Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to 12 Hours (AUC 0-12) Following Single Dose, Fasted, no Fulvestrant.

(NCT01597388)
Timeframe: 1 Day

Intervention	h*ng/mL (Geometric Mean)
35 mg	3233
50 mg	4666
75 mg	8185
100 mg	11470

Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to Infinity (AUC 0-∞) Following Single Dose, Fasted, no Fulvestrant.

(NCT01597388)
Timeframe: 1 Day

Intervention	h*ng/mL (Geometric Mean)
35 mg	3494
50 mg	5543
75 mg	9843
100 mg	15110

AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-∞) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant

(NCT01597388)
Timeframe: 5 Days

Intervention	h*ng/mL (Mean)
35 mg BID Continuous	3731
50 mg BID Continuous	6392
75 mg QD Continuous	12360
100 mg QD Continuous	17360

AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant

(NCT01597388)
Timeframe: 5 Days

Intervention	h*ng/mL (Mean)
35 mg BID Continuous	3478
50 mg BID Continuous	5080
75 mg QD Continuous	9723
100 mg QD Continuous	12590

AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 15 Intermittent Dosing, With Fulvestrant

(NCT01597388)
Timeframe: 15 Days

Intervention	h*ng/mL (Mean)
125 mg BID Intermittent Days 1 and 2 (Fasted)	19810
125 mg BID Intermittent Days 1 and 2 (Fed)	13760
170 mg BID Intermittent Days 1 and 2 (Fasted)	26570
170 mg BID Intermittent Days 1 and 2 (Fed)	16150

AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 22 Continuous Dosing, With Fulvestrant

(NCT01597388)
Timeframe: 15 Days

Intervention	h*ng/mL (Mean)
35 mg BID Continuous	8611
50 mg BID Continuous	11810
75 mg QD Continuous	13510
100 mg QD Continuous	15580

AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-24) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant

(NCT01597388)
Timeframe: 5 Days

Intervention	h*ng/mL (Mean)
35 mg BID Continuous	3697
50 mg BID Continuous	6006
75 mg QD Continuous	11650
100 mg QD Continuous	15790

AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-t) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant

(NCT01597388)
Timeframe: 5 Days

Intervention	h*ng/mL (Mean)
35 mg BID Continuous	3458
50 mg BID Continuous	5832
75 mg QD Continuous	11500
100 mg QD Continuous	15660

AZD2014 Peak Plasma Concentration (Cmax) Following Single Dose, Fasted, no Fulvestrant.

(NCT01597388)
Timeframe: 1 Day

Intervention	ng/mL (Geometric Mean)
35 mg	889.4
50 mg	968.5
75 mg	1678
100 mg	1942

AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant

(NCT01597388)
Timeframe: 5 Days

Intervention	ng/mL (Mean)
35 mg BID Continuous	971.2
50 mg BID Continuous	1023
75 mg QD Continuous	1895
100 mg QD Continuous	2166

AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant

(NCT01597388)
Timeframe: 15 Days

Intervention	ng/mL (Mean)
125 mg BID Intermittent Days 1 and 2 (Fasted)	3165
125 mg BID Intermittent Days 1 and 2 (Fed)	1933
170 mg BID Intermittent Days 1 and 2 (Fasted)	4238
170 mg BID Intermittent Days 1 and 2 (Fed)	2454

AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant

(NCT01597388)
Timeframe: 22 Days

Intervention	ng/mL (Mean)
35 mg BID Continuous	1374
50 mg BID Continuous	1785
75 mg QD Continuous	2409
100 mg QD Continuously	2327

Duration of Response (DoR)

Duration of response is defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression. (NCT01597388)
Timeframe: Up to 12 months

Intervention	Months (Median)
50 mg BID Continuous	5.1
75 mg QD Continuous	9.7
100 mg QD Continuous	NA
125 mg BID Intermittent Days 1 and 2 (Fasted)	NA
125 mg BID Intermittent Days 1 and 2 (Fed)	NA
170 mg BID Intermittent Days 1 and 2 (Fasted)	NA
125 mg BID Intermittent Days 1 and 4 (Fasted)	10.4

Objective Response Rate

Objective Response Rate (ORR) is defined as the number (%) of patients with a confirmed overall response of either complete response (CR) or partial response (PR). (NCT01597388)
Timeframe: Up to 12 months

Intervention	Participants (Number)
35 mg BID Continuous	0
50 mg BID Continuous	2
75 mg QD Continuous	2
100 mg QD Continuous	1
125 mg BID Intermittent Days 1 and 2 (Fasted)	2
125 mg BID Intermittent Days 1 and 2 (Fed)	1
170 mg BID Intermittent Days 1 and 2 (Fasted)	1
170 mg BID Intermittent Days 1 and 2 (Fed)	0
125 mg BID Intermittent Days 1 and 4 (Fasted)	1

Percentage Change From Baseline at 16 Weeks in Target Lesion (TL) Size.

Baseline was defined as last evaluable assessment prior to starting treatment. Tumour size was the sum of the longest diameters of the target lesions. TLs are measurable tumour lesions. (NCT01597388)
Timeframe: Up to 12 months

Intervention	Percentage Change (Mean)
35 mg BID Continuous	NA
50 mg BID Continuous	-9.37
75 mg QD Continuous	-5.83
100 mg QD Continuous	NA
125 mg BID Intermittent Days 1 and 2 (Fasted)	-0.46
125 mg BID Intermittent Days 1 and 2 (Fed)	-3.57
170 mg BID Intermittent Days 1 and 2 (Fasted)	-10.96
170 mg BID Intermittent Days 1 and 2 (Fed)	NA
125 mg BID Intermittent Days 1 and 4 (Fasted)	NA

Progression Free Survival at 26 Weeks

(NCT01597388)
Timeframe: Up to 12 months

Intervention	Percentage (Number)
35 mg BID Continuous	33
50 mg BID Continuous	38
75 mg QD Continuous	21
100 mg QD Continuous	60
125 mg BID Intermittent Days 1 and 2 (Fasted)	35
125 mg BID Intermittent Days 1 and 2 (Fed)	50
170 mg BID Intermittent Days 1 and 2 (Fasted)	38
170 mg BID Intermittent Days 1 and 2 (Fed)	40
125 mg BID Intermittent Days 1 and 4 (Fasted)	100

Progression Free Survival

(NCT01597388)
Timeframe: Up to 12 months

Intervention	Weeks (Median)
35 mg BID Continuous	49.4
50 mg BID Continuous	35.6
75 mg QD Continuous	17.3
100 mg QD Continuous	78.3
125 mg BID Intermittent Days 1 and 2 (Fasted)	22.6
125 mg BID Intermittent Days 1 and 2 (Fed)	33.9
170 mg BID Intermittent Days 1 and 2 (Fasted)	60.1
170 mg BID Intermittent Days 1 and 2 (Fed)	83.4
125 mg BID Intermittent Days 1 and 4 (Fasted)	NA

Time to AZD2014 Peak Plasma Concentration (Tmax) Following Single Dose, Fasted, no Fulvestrant.

(NCT01597388)
Timeframe: 1 Day

Intervention	hour (Median)
35 mg	1.00
50 mg	1.00
75 mg	1.10
100 mg	1.80

Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant

(NCT01597388)
Timeframe: 15 Days

Intervention	hours (Median)
125 mg BID Intermittent Days 1 and 2 (Fasted)	1.1
125 mg BID Intermittent Days 1 and 2 (Fed)	2.0
170 mg BID Intermittent Days 1 and 2 (Fasted)	1.5
170 mg BID Intermittent Days 1 and 2 (Fed)	3.0

Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant

(NCT01597388)
Timeframe: 22 Days

Intervention	hours (Median)
35 mg BID Continuous	1.3
50 mg BID Continuous	1.0
75 mg QD Continuous	1.5
100 mg QD Continuously	1.5

Adverse Events

(NCT01597388)
Timeframe: Up to 12 Months

,,,,,,,,

Intervention	Participants (Number)
	Any Adverse Event (AE)	Any AE, Causally Related to AZD2014	Any AE, Causally Related to Fulvestrant Only	Any AE of CTCAE Grade ≥ 3 (G3)	AEs of CTCAE G3, Causally Related to AZD2014	Any AE of CTCAE G3, Related to Fulvestrant Only	Any Adverse Event with Outcome of Death	AE with Outcome of Death, Related to AZD2014	AE Outcome of Death, Related to Fulvestrant Only	Any Serious Adverse Event (SAE)	Any SAE, Causally Related to AZD2014	Any SAE, Causally Related to Fulvestrant Only	Any AE Leading to Discontinuation of AZD2014	Any SAE Leading to Discontinuation of AZD2014
100 mg QD Continuous	10	9	3	6	5	0	0	0	0	1	0	0	3	0
125 mg BID Intermittent Days 1 and 2 (Fasted)	37	35	12	24	16	0	0	0	0	7	2	0	2	1
125 mg BID Intermittent Days 1 and 2 (Fed)	4	4	0	3	0	0	0	0	0	0	0	0	0	0
125 mg BID Intermittent Days 1 and 4 (Fasted)	2	2	1	1	0	0	0	0	0	0	0	0	0	0
170 mg BID Intermittent Days 1 and 2 (Fasted)	8	8	2	6	6	0	0	0	0	3	1	0	2	1
170 mg BID Intermittent Days 1 and 2 (Fed)	5	5	0	3	2	0	0	0	0	1	0	0	0	0
35 mg BID Continuous	6	5	2	3	2	0	0	0	0	0	0	0	2	0
50 mg BID Continuous	13	12	3	8	8	0	0	0	0	1	0	0	4	0
75 mg QD Continuous	14	14	6	10	7	0	1	0	0	3	1	0	2	1

Best Objective Response (BOR)

Best objective response was the best response a patient had following start of treatment but prior to starting any subsequent cancer therapy and prior to RECIST v1.1 progression or the last evaluable assessment in the absence of RECIST v1.1 progression. (NCT01597388)
Timeframe: Up to 12 months

,,,,,,,,

Intervention	Participants (Number)
	Complete Response	Partial Response	Stable Disease ≥ 8 weeks	Progression	Not Evaluable
100 mg QD Continuous	0	1	1	0	2
125 mg BID Intermittent Days 1 and 2 (Fasted)	0	2	17	7	1
125 mg BID Intermittent Days 1 and 2 (Fed)	0	1	2	0	0
125 mg BID Intermittent Days 1 and 4 (Fasted)	0	1	0	0	0
170 mg BID Intermittent Days 1 and 2 (Fasted)	0	1	3	0	1
170 mg BID Intermittent Days 1 and 2 (Fed)	0	0	1	1	1
35 mg BID Continuous	0	0	1	1	0
50 mg BID Continuous	0	2	4	2	3
75 mg QD Continuous	0	2	7	3	1

Body Temperature

(NCT01597388)
Timeframe: 28 Days

,,,,,,,,

Intervention	°C (Mean)
	Baseline	Cycle 1, Day 1	Cycle 1, Day 8	Cycle 1, Day 15	Cycle 1, Day 22	Cycle 2, Day 1
100 mg QD Continuous	36.48	36.46	36.35	36.35	36.26	36.54
125 mg BID Intermittent Days 1 and 2 (Fasted)	36.57	36.57	36.51	36.50	36.54	36.56
125 mg BID Intermittent Days 1 and 2 (Fed)	36.60	36.60	36.25	36.30	36.65	36.90
125 mg BID Intermittent Days 1 and 4 (Fasted)	NA	NA	NA	NA	NA	NA
170 mg BID Intermittent Days 1 and 2 (Fasted)	36.39	36.39	36.36	36.77	36.66	36.50
170 mg BID Intermittent Days 1 and 2 (Fed)	36.40	36.40	36.88	36.42	36.88	36.54
35 mg BID Continuous	36.35	36.33	36.33	36.48	36.13	36.25
50 mg BID Continuous	36.44	36.57	36.42	36.74	36.38	36.55
75 mg QD Continuous	36.46	36.34	36.59	36.45	36.38	36.57

Clinical Benefit Rate (CBR) at 24 Weeks

The Clinical Benefit Rate (CBR) at 24 weeks is defined as the percentage of patients who had a confirmed BOR of CR or PR in the first 24 weeks or who demonstrated SD for a minimum interval of 24 weeks (minus 1 week to allow for an early assessment within the assessment window, i.e., 161 days) following the start of treatment. (NCT01597388)
Timeframe: Up to 12 months

,,,,,,,,

Intervention	Participants (Number)
	Yes	No
100 mg QD Continuous	7	3
125 mg BID Intermittent Days 1 and 2 (Fasted)	11	26
125 mg BID Intermittent Days 1 and 2 (Fed)	2	2
125 mg BID Intermittent Days 1 and 4 (Fasted)	2	0
170 mg BID Intermittent Days 1 and 2 (Fasted)	3	5
170 mg BID Intermittent Days 1 and 2 (Fed)	2	3
35 mg BID Continuous	2	4
50 mg BID Continuous	6	7
75 mg QD Continuous	4	10

Clinically Important Changes in Clinical Chemistry Parameters

(NCT01597388)
Timeframe: Up to 12 Months

,,,,,,,,

Intervention	Participants (Number)
	Change in ALT ≥ 2 CTCAE Grades	Change in ALT to CTCAE Grade 3 or 4	Change in AST ≥ 2 CTCAE Grades	Change in AST to CTCAE Grade 3 or 4	Change in Alk Phosphatase ≥ 2 CTCAE Grades	Change in Alk Phosphatase to CTCAE Grade 3 or 4	Change in Albumin ≥ 2 CTCAE Grades	Change in Albumin to CTCAE Grade 3 or 4	Change in Bilirubin ≥ 2 CTCAE Grades	Change in Bilirubin to CTCAE Grade 3 or 4	Change in Creatinine ≥ 2 CTCAE Grades	Change in Creatinine to CTCAE Grade 3 or 4	Change in Phosphate ≥ 2 CTCAE Grades	Change in Phosphate to CTCAE Grade 3 or 4	Change in Urate ≥ 2 CTCAE Grades	Change in Urate to CTCAE Grade 3 or 4	Change in Calcium ≥ 2 CTCAE Grades	Change in Calcium to CTCAE Grade 3 or 4	Change in Sodium ≥ 2 CTCAE Grades	Change in Sodium to CTCAE Grade 3 or 4	Change in Potassium ≥ 2 CTCAE Grades	Change in Potassium to CTCAE Grade 3 or 4	Change in Magnesium ≥ 2 CTCAE Grades	Change in Magnesium to CTCAE Grade 3 or 4	Change in Fasting Glucose ≥ 2 CTCAE Grades	Change in Fasting Glucose to CTCAE Grade 3 or 4	Change in NonFasting Glucose ≥ 2 CTCAE Grades	Change in Non Fasting Glucose to CTCAE Gr.3 or 4
100 mg QD Continuous	3	1	2	2	0	0	2	0	0	0	1	0	2	0	0	0	0	0	3	2	5	5	2	2	1	0	0	0
125 mg BID Intermittent Days 1 and 2 (Fasted)	0	0	2	3	1	1	6	0	3	1	1	1	15	7	1	1	6	1	1	1	5	5	1	1	7	2	2	2
125 mg BID Intermittent Days 1 and 2 (Fed)	1	1	0	1	0	0	1	0	0	0	0	0	1	0	1	1	1	0	0	0	1	1	0	0	1	0	0	0
125 mg BID Intermittent Days 1 and 4 (Fasted)	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
170 mg BID Intermittent Days 1 and 2 (Fasted)	0	0	0	0	1	1	2	0	2	0	0	0	1	0	0	0	2	1	0	0	0	0	2	1	4	0	0	0
170 mg BID Intermittent Days 1 and 2 (Fed)	0	0	0	0	0	0	1	0	1	0	0	0	2	1	0	0	2	1	0	0	0	0	0	0	0	1	2	1
35 mg BID Continuous	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0
50 mg BID Continuous	1	0	2	0	2	1	1	0	0	0	1	0	2	0	1	1	3	1	1	0	1	0	1	0	1	0	0	0
75 mg QD Continuous	3	2	3	5	1	1	2	1	1	0	1	0	0	0	0	0	1	1	0	0	2	1	0	0	1	0	0	0

Clinically Important Changes in Haematology Parameters

(NCT01597388)
Timeframe: Up to 12 Months

,,,,,,,,

Intervention	Participants (Number)
	Change in Hemoglobin ≥ 2 CTCAE Grades	Change in Hemoglobin to CTCAE Grade 3 or 4	Change in Leukocytes ≥ 2 CTCAE Grades	Change in Leukocytes to CTCAE Grade 3 or 4	Change in Lymphocytes ≥ 2 CTCAE Grades	Change in Lymphocytes to CTCAE Grade 3 or 4	Change in Neutrophils ≥ 2 CTCAE Grades	Change in Neutrophils to CTCAE Grade 3 or 4	Change in Platelets ≥ 2 CTCAE Grades	Change in Platelets to CTCAE Grade 3 or 4	Change in aPTT ≥ 2 CTCAE Grades	Change in aPTT to CTCAE Grade 3 or 4	Change in INR ≥ 2 CTCAE Grades	Change in INR to CTCAE Grade 3 or 4
100 mg QD Continuous	0	0	1	0	5	0	3	0	0	0	0	0	0	0
125 mg BID Intermittent Days 1 and 2 (Fasted)	0	0	9	1	10	7	12	2	2	1	3	1	1	0
125 mg BID Intermittent Days 1 and 2 (Fed)	0	0	2	0	0	1	1	0	1	1	0	0	0	0
125 mg BID Intermittent Days 1 and 4 (Fasted)	0	0	0	0	1	1	0	0	0	0	0	0	0	0
170 mg BID Intermittent Days 1 and 2 (Fasted)	0	0	2	0	1	1	1	0	1	1	1	0	0	0
170 mg BID Intermittent Days 1 and 2 (Fed)	0	0	3	0	2	1	1	0	0	0	1	1	0	0
35 mg BID Continuous	0	0	0	0	2	0	1	0	0	0	0	0	0	0
50 mg BID Continuous	0	0	4	1	6	3	4	1	0	0	1	0	0	0
75 mg QD Continuous	0	0	2	1	8	3	1	1	2	1	0	0	0	0

Heart Rate

(NCT01597388)
Timeframe: 28 Days

,,,,,,,,

Intervention	beats/min (Mean)
	Baseline	Cycle 1, Day 1	Cycle 1, Day 8	Cycle 1, Day 15	Cycle 1, Day 22	Cycle 2, Day 1
100 mg QD Continuous	81.0	86.8	92.6	82.8	86.1	87.9
125 mg BID Intermittent Days 1 and 2 (Fasted)	83.5	83.5	84.4	81.3	84.6	85.7
125 mg BID Intermittent Days 1 and 2 (Fed)	73.5	73.5	71.5	83.3	77.8	78.0
125 mg BID Intermittent Days 1 and 4 (Fasted)	NA	NA	NA	NA	NA	NA
170 mg BID Intermittent Days 1 and 2 (Fasted)	86.1	86.1	79.4	82.5	87.4	83.0
170 mg BID Intermittent Days 1 and 2 (Fed)	79.6	79.6	75.5	77.4	88.8	85.0
35 mg BID Continuous	87.5	87.3	80.8	80.2	82.4	83.5
50 mg BID Continuous	84.5	77.7	81.2	89.3	87.8	89.7
75 mg QD Continuous	82.7	87.3	85.4	86.7	85.3	84.0

Left Ventricular Ejection Fraction

(NCT01597388)
Timeframe: 24 hours

,,,,,,,,

Intervention	% Left Ventricular Ejection Fraction (Mean)
	Screening	End of Study	Change from Baseline to End of Study
100 mg QD Continuous	61.4	61.8	0.0
125 mg BID Intermittent Days 1 and 2 (Fasted)	62.6	62.5	-1.3
125 mg BID Intermittent Days 1 and 2 (Fed)	62.5	NA	NA
125 mg BID Intermittent Days 1 and 4 (Fasted)	NA	NA	NA
170 mg BID Intermittent Days 1 and 2 (Fasted)	66.9	NA	NA
170 mg BID Intermittent Days 1 and 2 (Fed)	63.8	NA	NA
35 mg BID Continuous	59.2	NA	NA
50 mg BID Continuous	64.0	64.0	1.4
75 mg QD Continuous	60.9	62.3	-1.5

Oxygen Saturation

(NCT01597388)
Timeframe: 28 Days

,,,,,,,,

Intervention	% Arterial Oxygen Saturation (Mean)
	Baseline	Cycle 1, Day 1	Cycle 1, Day 8	Cycle 1, Day 15	Cycle 1, Day 22	Cycle 2, Day 1
100 mg QD Continuous	96.7	96.9	97.1	97.1	97.6	97.3
125 mg BID Intermittent Days 1 and 2 (Fasted)	97.8	97.8	97.8	98.0	98.1	98.2
125 mg BID Intermittent Days 1 and 2 (Fed)	97.0	97.0	97.0	97.0	97.5	96.5
125 mg BID Intermittent Days 1 and 4 (Fasted)	NA	NA	NA	NA	NA	NA
170 mg BID Intermittent Days 1 and 2 (Fasted)	97.0	97.0	97.7	97.0	97.9	96.2
170 mg BID Intermittent Days 1 and 2 (Fed)	97.6	97.6	98.3	96.8	98.0	97.0
35 mg BID Continuous	97.0	97.5	98.3	97.7	96.8	97.5
50 mg BID Continuous	97.2	97.7	97.5	96.5	97.3	97.3
75 mg QD Continuous	96.8	97.4	97.1	97.3	96.8	96.9

Post-Baseline Glucose Elevation

(NCT01597388)
Timeframe: 28 Days

,,,,,,,,

Intervention	Participants (Number)
	Participants with ≥ 1 post-baseline elevation	Subjects with Max Post-Baseline CTCAE Grade ≥ 1	Subjects with Max Post-Baseline CTCAE Grade ≥ 2	Subjects with Max Post-Baseline CTCAE Grade ≥ 3	Subjects with Max Post-Baseline CTCAE Grade ≥ 4
100 mg QD Continuous	5	3	1	1	0
125 mg BID Intermittent Days 1 and 2 (Fasted)	29	17	7	5	0
125 mg BID Intermittent Days 1 and 2 (Fed)	3	2	1	0	0
125 mg BID Intermittent Days 1 and 4 (Fasted)	0	0	0	0	0
170 mg BID Intermittent Days 1 and 2 (Fasted)	6	2	1	3	0
170 mg BID Intermittent Days 1 and 2 (Fed)	5	4	0	1	0
35 mg BID Continuous	3	2	1	0	0
50 mg BID Continuous	6	5	0	1	0
75 mg QD Continuous	7	5	0	2	0

QTcF Over 24 Hours

(NCT01597388)
Timeframe: 24 hours

,,,,,,,,

Intervention	msec (Mean)
	Baseline	0.25 Hours Postdose	0.5 Hours Postdose	1 Hour Postdose	1.5 Hours Postdose	2 Hours Postdose	4 Hours Postdose	6 Hours Postdose	8 Hours Postdose	12 Hours Postdose	24 Hours Postdose
100 mg QD Continuous	415.95	418.44	418.91	416.20	415.33	414.01	410.88	414.74	413.56	414.59	415.29
125 mg BID Intermittent Days 1 and 2 (Fasted)	419.95	NA	413.28	416.22	417.10	414.99	414.04	412.80	414.17	414.09	422.73
125 mg BID Intermittent Days 1 and 2 (Fed)	427.13	NA	418.90	427.77	434.33	424.00	424.43	417.00	419.90	431.70	426.77
125 mg BID Intermittent Days 1 and 4 (Fasted)	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
170 mg BID Intermittent Days 1 and 2 (Fasted)	424.84	NA	415.67	419.61	420.43	418.60	426.60	422.94	416.80	420.66	NA
170 mg BID Intermittent Days 1 and 2 (Fed)	435.26	NA	420.06	421.20	427.48	422.94	422.40	418.34	425.54	432.46	NA
35 mg BID Continuous	423.12	429.66	431.84	431.00	431.82	433.02	422.00	421.50	424.86	427.74	425.54
50 mg BID Continuous	421.92	420.13	419.18	422.21	425.15	423.31	419.97	419.14	420.16	425.46	421.45
75 mg QD Continuous	412.78	413.04	415.08	416.08	415.36	415.84	411.18	411.85	411.16	409.67	409.33

Respiratory Rate

(NCT01597388)
Timeframe: 28 Days

,,,,,,,,

Intervention	breaths/min (Mean)
	Baseline	Cycle 1, Day 1	Cycle 1, Day 8	Cycle 1, Day 15	Cycle 1, Day 22	Cycle 2, Day 1
100 mg QD Continuous	17.8	17.3	17.5	17.9	17.1	18.3
125 mg BID Intermittent Days 1 and 2 (Fasted)	17.5	17.5	17.2	17.6	17.6	17.3
125 mg BID Intermittent Days 1 and 2 (Fed)	17.5	17.5	16.8	17.0	17.8	17.8
125 mg BID Intermittent Days 1 and 4 (Fasted)	NA	NA	NA	NA	NA	NA
170 mg BID Intermittent Days 1 and 2 (Fasted)	18.1	18.1	17.3	17.7	17.6	17.3
170 mg BID Intermittent Days 1 and 2 (Fed)	17.6	17.6	18.0	17.4	18.0	17.5
35 mg BID Continuous	18.3	16.0	17.3	17.2	17.3	17.3
50 mg BID Continuous	17.5	16.6	16.4	17.1	17.8	17.6
75 mg QD Continuous	18.3	17.7	17.6	18.5	18.0	17.8

Sitting Diastolic Blood Pressure

(NCT01597388)
Timeframe: 28 Days

,,,,,,,,

Intervention	mmHg (Mean)
	Baseline	Cycle 1, Day 1	Cycle 1, Day 8	Cycle 1, Day 15	Cycle 1, Day 22	Cycle 2, Day 1
100 mg QD Continuous	74.9	76.5	72.6	68.7	77.0	74.1
125 mg BID Intermittent Days 1 and 2 (Fasted)	74.4	74.4	72.4	73.1	70.9	71.4
125 mg BID Intermittent Days 1 and 2 (Fed)	73.8	73.8	70.8	70.0	74.8	73.3
125 mg BID Intermittent Days 1 and 4 (Fasted)	NA	NA	NA	NA	NA	NA
170 mg BID Intermittent Days 1 and 2 (Fasted)	75.5	75.5	78.3	74.2	75.0	72.5
170 mg BID Intermittent Days 1 and 2 (Fed)	76.6	76.6	75.8	69.0	73.2	68.0
35 mg BID Continuous	72.8	74.8	74.5	74.7	72.5	72.0
50 mg BID Continuous	75.4	77.4	74.3	72.8	73.9	73.3
75 mg QD Continuous	77.4	75.4	75.3	75.4	76.2	72.7

Sitting Systolic Blood Pressure

(NCT01597388)
Timeframe: 28 Days

,,,,,,,,

Intervention	mmHg (Mean)
	Baseline	Cycle 1, Day 1	Cycle 1, Day 8	Cycle 1, Day 15	Cycle 1, Day 22	Cycle 2, Day 1
100 mg QD Continuous	125.2	124.7	122.2	115.2	125.4	116.6
125 mg BID Intermittent Days 1 and 2 (Fasted)	124.4	124.4	122.2	122.8	116.6	119.3
125 mg BID Intermittent Days 1 and 2 (Fed)	122.3	122.3	115.3	112.8	115.5	112.5
125 mg BID Intermittent Days 1 and 4 (Fasted)	NA	NA	NA	NA	NA	NA
170 mg BID Intermittent Days 1 and 2 (Fasted)	120.8	120.8	127.9	128.3	119.9	113.2
170 mg BID Intermittent Days 1 and 2 (Fed)	137.8	137.8	124.8	126.6	109.2	117.0
35 mg BID Continuous	114.2	113.5	124.0	119.7	116.7	111.7
50 mg BID Continuous	126.3	125.1	120.4	115.5	124.7	119.7
75 mg QD Continuous	127.4	122.6	123.7	121.6	123.5	123.6

Duration of Response/Time to Disease Progression in Patients With Measurable Disease

Duration of response is defined for all evaluable patients with measurable disease who have achieved a confirmed response as the date at which the patient's earliest best objective status is first noted to be either a CR or PR to the earliest date progression is documented. If a patient dies subsequent to the confirmed response without a documentation of disease progression, the patient will be considered to have had disease progression at the time of their death. In the case of a patient failing to return for evaluations before a documentation of disease progression, the patient will be censored for progression on the date of last evaluation. The distribution of duration of response will be estimated using the method of Kaplan-Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT00423917)
Timeframe: Up to 5 years

Intervention	months (Median)
Fulvestrant + Bevacizumab	11.9

Objective Response Rate as Measured by RECIST Criteria in Patients With Measurable Disease

A confirmed response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. The confirmed response rate will be estimated by the number of confirmed responses in evaluable patients with measurable disease divided by the total number of evaluable patients with measurable disease. The appropriate confidence interval will be calculated. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. (NCT00423917)
Timeframe: Up to 5 years

Intervention	percentage of patients (Number)
Fulvestrant + Bevacizumab	22

Overall Survival

Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier (1958). (NCT00423917)
Timeframe: Up to 5 years

Intervention	months (Median)
Fulvestrant + Bevacizumab	26.9

Progression Free Survival

Time to disease progression is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had disease progression at the time of their death. If the patient is declared to be a major treatment violation, the patient will be censored on the date the treatment violation was declared to have occurred. In the case of a patient starting treatment and then never returning for any evaluations, the patient will be censored for progression 1 day post-registration. The distribution of time to progression will be estimated using the method of Kaplan-Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT00423917)
Timeframe: Up to 5 years

Intervention	months (Median)
Fulvestrant + Bevacizumab	6.2

Six-month Progression-free Survival (PFS) Rate at 6 Months

The primary endpoint of this trial is the 6-month progression-free survival rate. A patient is considered to be a 6-month progression-free survivor if the patient is on study treatment 6 months from registration without a documentation of disease progression. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Additionally, if some patients are lost to follow-up not having been observed for at least 6 months, an estimate and 95% confidence interval for the 6-month progression-free survival rate incorporating censoring will be computed using the method of Kaplan-Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT00423917)
Timeframe: at 6 months

Intervention	percentage of patients (Number)
Fulvestrant + Bevacizumab	39

Time to First Cytotoxic Agent

Time to first dose of a cytotoxic agent is defined to be the time from the date of registration to the date at which a patient recieves the first dose of a cytotoxic agent. The distribution of time to first dose of a cytotoxic agent will be estimated using the method of Kaplan-Meier (1958). (NCT00423917)
Timeframe: Up to 5 years

Intervention	months (Median)
Fulvestrant + Bevacizumab	9.9

Quality of Life, as Measured by the Largest Mean Change in LASA Overall QOL and Physical Well-being Items

Quality of life (QOL) assessment will be a secondary exploratory component of this trial. QOL of patients was measure using the 6-item Linear Analogue Self-Assessment (LASA).The LASA consists of six single-item numeric analog scales measuring overall QOL; mental, physical, emotional, and spiritual well-being; and level of activity each on a scale of 0 ('As bad as it can be') to 10 ('As good as it can be') during the past week. Items were transformed to a 0 (worst QOL or well-being) to 100 (best QOL or well-being) scale for statistical analysis. Mean change from baseline of the largest mean change in overall QOL and physical well-being are reported below. (NCT00423917)
Timeframe: Up to 5 years

Intervention	mean change in LASA QOL scaled score (Mean)
	Overall Quality of Life	Physical Well-Being
Fulvestrant + Bevacizumab	-5.0	-6.8

Clinical Benefit Rate at 24 Weeks (CBR24)

"Clinical benefit rate was defined as patients with best objective response of complete response or partial response in the first 25 weeks or who have stable disease for at least 23 weeks after randomization.~Adjusted response rate was presented in this analysis.~Data from the 300mg arm should be interpreted with caution as recruitment to the 300mg arm was stopped early at 20 patients randomised and therefore the 300mg data is highly variable." (NCT04214288)
Timeframe: At Week 24

Intervention	Percentage (%) (Number)
AZD9833 75mg	48.8
AZD9833 150mg	51.0
AZD9833 300mg	42.4
Fulvestrant 500 mg	39.1

Objective Response Rate (ORR)

"ORR was assessed by the Investigator as defined by RECIST version 1.1. The ORR was defined as investigator assessed Complete Response or Partial Response prior to progression in patients with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST v1.1).~Adjusted response rate was presented in this analysis.~Data from the 300mg arm should be interpreted with caution as recruitment to the 300mg arm was stopped early at 20 patients randomised and therefore the 300mg data is highly variable." (NCT04214288)
Timeframe: From screening until disease progression (up to data cut-off of 29 months)

Intervention	Percentage (%) (Number)
AZD9833 75mg	15.7
AZD9833 150mg	17.1
AZD9833 300mg	25.2
Fulvestrant 500 mg	11.6

Progression-free Survival (PFS)

"PFS was assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST) version 1.1. PFS was defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or received another anti-cancer therapy prior to progression. Disease progression was defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions.~Data from the 300mg arm should be interpreted with caution as recruitment to the 300mg arm was stopped early at 20 patients randomised and therefore the 300mg data is highly variable." (NCT04214288)
Timeframe: From date of randomisation to date of objective disease progression (or last evaluable assessment in the absence of progression) or death (up to data cut-off of 29 months)

Intervention	Months (Median)
AZD9833 75mg	7.2
AZD9833 150mg	7.7
AZD9833 300mg	6.3
Fulvestrant 500 mg	3.7

Number of Patients With Adverse Events

The safety and tolerability of AZD9833 when compared to fulvestrant in women with advanced ER-positive HER2-negative breast cancer was evaluated. (NCT04214288)
Timeframe: From the date of first dose up to the safety follow-up period (28 days after last dose of AZD9833 and 56 days after last dose of fulvestrant) (up to data cut-off of 29 months)

,,,

Intervention	Participants (Count of Participants)
	Any Adverse Event (AE)	Any AE causally related to treatment	Any AE of CTCAE grade 3 or higher	Any AE of CTCAE grade 3 or higher, causally related to treatment	Any AE with outcome = death	Any AE with outcome = death, causally related to treatment	Any Serious Adverse Event (SAE)	Any SAE, causally related to treatment	Any SAE causing discontinuation of treatment	Any SAE causing discontinuation of treatment, causally related to treatment	Any AE leading to discontinuation of treatment	Any AE leading to discontinuation of treatment, causally related to treatment	Any AE leading to dose reduction	Any AE leading to dose interruption
AZD9833 150mg	66	49	17	2	1	0	7	2	0	0	0	0	9	16
AZD9833 300mg	19	14	3	1	0	0	2	1	0	0	2	0	4	4
AZD9833 75mg	57	39	9	1	0	0	6	3	1	1	2	2	1	11
Fulvestrant 500 mg	50	13	11	0	0	0	4	0	0	0	0	0	0	3

Plasma Concentrations of AZD9833

The plasma concentrations of AZD9833 at steady state were evaluated. (NCT04214288)
Timeframe: Cycle 1 Day 15 (pre-dose), Cycle 1 Day 15 (2h), Cycle 1 Day 15 (4h) and Cycle 2 Day 1 (pre-dose), (each cycle is 28 days in length)

Intervention	ng/ml (Geometric Mean)
	Cycle 1 Day 15 (pre-dose)	Cycle 1 Day 15 (2h)	Cycle 1 Day 15 (4h)	Cycle 2 Day 1 (pre-dose)
AZD9833 150mg	41.0856	96.2038	95.5360	34.2592
AZD9833 300mg	108.1351	302.1254	289.1464	115.8558
AZD9833 75mg	22.8387	51.9098	54.5098	24.2895

Clinical Benefit Rate

Clinical benefit = complete response (CR), partial response (PR), or stable disease (SD) lasting for at least 6 months, assessed per Response Evaluation Criteria of Solid Tumor (RECIST).CR=disappearance of all target and non-target lesions. PR= disappearance of or at least 30% decrease in the sum of the longest diameters of target lesions, with non-progressive disease in non-target lesions. SD= sum of the longest diameters of target lesions decrease <30% or increase <20%, with non-progressive disease in non-target lesions. 141 eligible, treated patients were included. (NCT00057941)
Timeframe: assessed every 3 cycles while on treatment, assessed every 3 months when follow up <2 years, every 6 months between 2-3 years,no specific requirements after 3 years

Intervention	percentage of participants (Number)
Anastrozole and ZD1839	44
Fulvestrant and ZD1839	41

Incidence of Adverse Events

Defined as the proportion of patients with documentation of grade 3 - 5 toxicity (regardless of attribution using the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v.] 5.0 criteria). A 95% binomial confidence interval for single proportions will be constructed for the severe toxicity rate during treatment. Univariate relationships between the primary endpoint and various pre-treatment patient characteristics such as anemia, self-assessed functional status, or social support will be described via cross-tabulation and Fisher's exact testing. Exploratory logistic regression modeling, with limited generalizability due to the modest sample size, will be used to assess the relative contributions of these variables impact the likelihood of developing a severe toxicity during treatment. The strength of this association will be expressed in terms of an odds ratio and its associated 95% confidence interval. (NCT03633331)
Timeframe: 6 months

Intervention	proportion of patients (Number)
Treatment (Palbociclib, Letrozole or Fulvestrant)	0.756

Change From Baseline Between Treatment Comparison in EQ-5D Visual Analog Scale (VAS) Scores Scale

The EuroQol-5D (version 3L) is a brief self-administered, validated instrument consisting of 2 parts. The second part consists of the EQ-5D general health status as measured by a visual analog scale (EQ-5D VAS). EQ-5D VAS measures the participant's self-rated health status on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state). (NCT01942135)
Timeframe: From Cycle 1 to 14, as of 05 December 2014.

Intervention	Units on a scale (Mean)
Palbociclib + Fulvestrant	-1.8
Placebo + Fulvestrant	-2.6

Change From Baseline Between Treatment Comparison in EuroQoL 5D (EQ-5D)- Health Index Scores

The EuroQol-5D (version 3L) is a brief self-administered, validated instrument consisting of 2 parts. The first part consists of 5 descriptors of current health state (mobility, self care, usual activities, pain/discomfort, and anxiety/ depression); a participant is asked to rate each state on a three level scale (1=no problem, 2=some problem, and 3=extreme problem) with higher levels indicating greater severity/ impairment Published weights are available that allow for the creation of a single summary score called the EQ-5D index, which basically ranges from 0 to 1 with low scores representing a higher level of dysfunction and 1 as perfect health. The second part consists of the EQ-5D general health status as measured by a visual analog scale (EQ-5D VAS). EQ-5D VAS measures the participant's self-rated health status on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state). (NCT01942135)
Timeframe: From Cycle 1 to 14, as of 05 December 2014.

Intervention	Units on a scale (Mean)
Palbociclib + Fulvestrant	0.006
Placebo + Fulvestrant	-0.031

Clinical Benefit Response (CBR)

CBR is defined as the overall complete response (CR), partial response (PR) , or stable disease (SD) ≥24 weeks according to the RECIST version 1.1. Clinical Benefit Response Rate (CBRR) is defined as the proportion of participants with CR, PR, or SD ≥24 weeks relative to all randomized participants and randomized participants with measurable disease at baseline. Participants who do not have on-study radiographic tumor re-evaluation, who received antitumor treatment other than the study medication prior to reaching a CR or PR, a best response of SD ≥24 weeks, or who died, progressed, or dropped out for any reason prior to reaching a CR or PR and a best response of SD ≥24 weeks was counted as non-responders in the assessment of CBR. Per RECIST v1.1 for target lesions and assessed by MRI: CR, disappearance of all target lesions; PR, ≥30% decrease in the sum of the longest diameter of target lesions; OR = CR + PR. (NCT01942135)
Timeframe: From randomization until end of treatment (assessed up to 12 months)

Intervention	percentage of participants (Number)
Palbociclib + Fulvestrant	34.0
Placebo + Fulvestrant	19.0

Duration of Response (DR)

DR is defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of disease progression or to death due to any cause, whichever occurs first. If tumor progression data included more than 1 date, the first date was used. DR was calculated as [the date response ended (ie, date of PD or death) - first CR or PR date + 1)]/30.4. Kaplan-Meier estimate of median of the DR is provided below. No inferential statistical analysis were done for DR. The DR was only calculated for the participants with a CR or PR. (NCT01942135)
Timeframe: From randomization until end of treatment (assessed up to 12 months)

Intervention	Months (Median)
Palbociclib + Fulvestrant	9.3
Placebo + Fulvestrant	5.7

Objective Response (OR)

OR is defined as the overall complete response (CR) or partial response (PR) according to the RECIST version 1.1 Objective Response Rate (ORR) is defined as the proportion of participants with CR or PR relative to all randomized participants and randomized participants with measurable disease at baseline. Participants who do not have on-study radiographic tumor re-evaluation, who received anti-tumor treatment other than the study medication prior to reaching a CR or PR, or who died, progressed, or dropped out for any reason prior to reaching a CR or PR were counted as non-responders in the assessment of ORR. Per response evaluation criteria in solid tumors criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), ≥30% decrease in the sum of the longest diameter of target lesions (longest for non-nodal and short axis for nodal target lesions); Overall Response (OR) = CR + PR. (NCT01942135)
Timeframe: From randomization until end of treatment (assessed up to 12 months)

Intervention	percentage of participants (Number)
Palbociclib + Fulvestrant	10.4
Placebo + Fulvestrant	6.3

Overall Survival (OS) - Number of Participants Who Died

OS is defined as the time from date of randomization to date of death due to any cause. In the absence of confirmation of death, survival time was censored to last date the participant was known to be alive. For participants lacking survival data beyond the date of their last follow-up, the OS time was censored on the last date they were known to be alive. Participants lacking survival data beyond randomization were to have their OS times be censored at randomization. The length of OS was calculated as OS time (months) = [death date (censor date) - randomization date + 1]/30.4. No inferential statistical analysis were done because of the immaturity of the OS data. (NCT01942135)
Timeframe: From randomization until death (up to approximately 36 months)

Intervention	deaths (Number)
Palbociclib + Fulvestrant	19
Placebo + Fulvestrant	9

Progression-Free Survival (PFS) as Assessed by the Investigator

PFS is the time from the date of randomization to the date of the first documentation of objective progression of disease (PD)or death due to any cause in absence of documented PD. Participants lacking an evaluation of tumor response after randomization had their PFS time censored on the date of randomization with the duration of a day. Participants with documentation of PD or death after a long interval (2 or more incomplete or non-evaluable assessments) since the last tumor assessment were censored at the time of last objective assessment that did not show PD. The length of PFS was calculated as PFS time (months) =[progression/death date(censor date) - randomization date + 1]/30.4. Progression is defined using Response Evaluation Criteria in Solid Tumors(RECIST v1.1) a 20% increase in the sum of diameters of target lesions and the sum must also demonstrate an absolute increase of at least 5mm or unequivocal progression of existing non-target lesions or the appearance of new lesions. (NCT01942135)
Timeframe: From randomization date to date of first documentation of progression or death (assessed up to 12 months)

Intervention	Months (Median)
Palbociclib + Fulvestrant	9.2
Placebo + Fulvestrant	3.8

Change From Baseline Between Treatment Comparison in EORTC QLQ BR23 Symptom Scale Scores

The EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual functioning, sexual enjoyment, future perspective) and four symptom scales (systemic side effects, breast symptoms, arm symptoms, upset by hair loss). QLQ-BR23 questionnaire employs 4-point scales with responses from 'not at all' to 'very much'. All scores are converted to a 0 to 100 scale. For symptom-oriented scales, a higher score represent more severe symptoms. (NCT01942135)
Timeframe: From Cycle 1 to 14, as of 05 December 2014.

Intervention	Units on a scale (Mean)
	Systemic therapy side effects	Breast symptoms	Arm symptoms	Upset by hair loss
Palbociclib + Fulvestrant	3.8	-2.2	-2.2	2.9
Placebo + Fulvestrant	3.4	-1.3	-2.0	-6.0

Change From Baseline Between Treatment Comparison in EORTC QLQ-C30 Symptom Scale Scores

"The EORTC-QLQ-C30 is a 30-item questionnaire composed of five multi-item functional subscales (physical, role, emotional, cognitive , and social functioning), three multi-item symptom scales (fatigue, nausea/vomiting, and pain), a global quality of life (QOL) subscale, and six single item symptom scales assessing other cancer-related symptoms (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and the financial impact of cancer). The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items are then converted to a 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represents more severe symptoms. A 10-point or higher change in scores from baseline is considered clinically significant." (NCT01942135)
Timeframe: From Cycle 1 to 14, as of 05 December 2014.

Intervention	Units on a scale (Mean)
	Fatigue	Nausea and vomiting	Pain	Dyspnoea	Insomnia	Appetite loss	Constipation	Diarrhoea	Financial difficulties
Palbociclib + Fulvestrant	1.8	1.7	-3.3	2.8	-2.4	1.1	3.5	1.9	-3.7
Placebo + Fulvestrant	3.3	4.2	2.0	3.3	-0.4	1.7	2.8	2.4	-4.0

Change From Baseline Between Treatment Comparison in European Organization for Research and Treatment of Cancer Breast Cancer Module (EORTC QLQ BR23) Functional Scale Scores

The EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual functioning, sexual enjoyment, future perspective) and four symptom scales (systemic side effects, breast symptoms, arm symptoms, upset by hair loss). QLQ-BR23 questionnaire employs 4-point scales with responses from 'not at all' to 'very much'. All scores are converted to a 0 to 100 scale. For functional scales, higher scores represent a better level of functioning. (NCT01942135)
Timeframe: From Cycle 1 to 14, as of 05 December 2014.

Intervention	Units on a scale (Mean)
	Body image	Sexual functioning	Sexual enjoyment	Future perspective
Palbociclib + Fulvestrant	1.9	-1.1	-5.2	8.1
Placebo + Fulvestrant	-0.3	-0.4	-6.6	4.5

Change From Baseline Between Treatment Comparison in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Functional Scale Scores

Intervention	Units on a scale (Mean)
	Global health status / QoL	Physical functioning	Role functioning	Emotional functioning	Cognitive functioning	Social functioning
Palbociclib + Fulvestrant	-0.9	-0.7	-1.8	2.7	-1.7	-0.5
Placebo + Fulvestrant	-4.0	-1.7	-3.7	-1.9	-2.9	-0.6

Ctrough for Fulvestrant

"Ctrough for Fulvestrant (if applicable). The method of dispersion applied here is percent coefficient of variation (%CV)." (NCT01942135)
Timeframe: Cycles 2/Day 1 and Cycle 3/Day 1

Intervention	ng/mL (Geometric Mean)
	Cycle 2/Day 1 (N= 35, 19)	Cycle 3/Day 1 (N= 29, 14)
Palbociclib + Fulvestrant	11.75	9.90
Placebo + Fulvestrant	9.31	7.60

Ctrough for Goserelin

"Cmin for goserelin (if applicable). The method of dispersion applied here is percent coefficient of variation (%CV)." (NCT01942135)
Timeframe: Cycles 2/ Day 1 and Cycle 3/ Day 1

Intervention	pg/mL (Geometric Mean)
	Cycle 2/Day 1 (N= 9, 5)	Cycle 3/Day 1 (N= 7, 3)
Palbociclib + Fulvestrant	295.1	344.8
Placebo + Fulvestrant	302.5	288.5

Observed Plasma Trough Concentration (Ctrough) for Palbociclib

"Ctrough for palbociclib (if applicable). The method of dispersion applied here is percent coefficient of variation (%CV)." (NCT01942135)
Timeframe: Cycle 1/Day 15 and Cycle 2/Day 15

Intervention	ng/mL (Geometric Mean)
	Cycle 1/Day 15 (N= 165)	Cycle 2/Day 15 (N= 160)
Palbociclib + Fulvestrant	70.70	75.29

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities)

An AE is any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE is any untoward medical occurrence at any dose that results in death; is life-threatening; requires hospitalization; results in persistent or significant disability or in congenital anomaly/birth defect. Severity will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0. (NCT01942135)
Timeframe: From the signing of the informed consent until 28 days after the last dose of study medication up to 14 months

Intervention	Percentage of Participants (Number)
	With AEs	With SAEs	With Grade 3 or 4 AEs	With Grade 5 AEs	Discontinued palbociclib/placebo due to AEs
Palbociclib + Fulvestrant	97.7	9.6	70.1	0.9	3.8
Placebo + Fulvestrant	89.0	14.0	18.0	1.2	4.1

Survival Probabilities at Months 12, 24 and 36

One-, Two- or Three-year Survival Probability is defined as the probability of survival 1 year, 2 or 3 years after the date of randomization based on the Kaplan-Meier estimate. Survival time was censored to last date the participant is known to be alive. (NCT01942135)
Timeframe: From randomization until death (assessed up to 36 months)

Intervention	percentage of participants (Number)
	Survival Probability at Month 12	Survival Probability at Month 24	Survival Probability at Month 36
Palbociclib + Fulvestrant	89.3	NA	NA
Placebo + Fulvestrant	89.3	NA	NA

Time to Deterioration (TTD)

A time to event analysis was pre-specified for pain. An analysis of TTD in pain defined as time between baseline and first occurrence of increase of ≥10 points in pain. Deterioration will be defined increase in score of 10 points or greater from baseline. The Kaplan-Meier estimates of quartiles (time to deterioration) with 95% CI is mentioned below. (NCT01942135)
Timeframe: Baseline, Day 1 of Cycles 2 to 4, Day 1 of every alternate cycle after that until the end of treatment

Intervention	Months (Median)
	25% quartile	50% quartile
Palbociclib + Fulvestrant	1.9	8.0
Placebo + Fulvestrant	1.0	2.8

Clinical Benefit Rate (CBR) With Confirmed Response Based on Local Investigator Assessment as Per RECIST 1.1

"Clinical benefit rate with confirmed response was defined as the percentage of participants with a best overall response of confirmed CR or confirmed PR or stable disease (SD) or Non-CR/Non-progressive disease (PD) lasting more than 24 weeks based on local investigator assessment as per RECIST 1.1.~CR: Disappearance of all non-nodal target lesions and all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions and all lymph nodes assigned as non-target lesions must have a reduction in short axis to < 10 mm.~PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.~SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease." (NCT04899349)
Timeframe: Up to 7.4 months

Intervention	Participants (Count of Participants)
Alpelisib + Fulvestrant + Dapagliflozin + Metformin XR	1

Number of Participants With Hyperglycemia Grade ≥ 3 Over the First Eight Weeks of Alpelisib Plus Fulvestrant Treatment

Number of participants with severe hyperglycemia over the first eight weeks of alpelisib plus fulvestrant treatment. Severe hyperglycemia (Grade ≥ 3) is defined as any glucose laboratory values > 250 milligram (mg)/ deciliter (dL) (> 13.9 millimole (mmol)/ liter (L)) (NCT04899349)
Timeframe: From Cycle 1 Day 8 to Cycle 3 Day 8 (first eight weeks of treatment with alpelisib). Cycle = 28 days.

Intervention	Participants (Count of Participants)
Alpelisib + Fulvestrant + Dapagliflozin + Metformin XR	1

Overall Response Rate (ORR) With Confirmed Response Based on Local Investigator Assessment as Per RECIST 1.1.

"ORR with confirmed response was defined as the percentage of participants with best overall response of confirmed complete response (CR) or confirmed partial response (PR) based on local investigator's assessment according to RECIST 1.1.~CR: Disappearance of all non-nodal target lesions and all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions and all lymph nodes assigned as non-target lesions must have a reduction in short axis to < 10 mm.~PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters." (NCT04899349)
Timeframe: Up to 7.4 months

Intervention	Participants (Count of Participants)
Alpelisib + Fulvestrant + Dapagliflozin + Metformin XR	1

Progression-free Survival (PFS) Based on Local Investigator Assessment

"PFS was defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS was assessed via a local investigator assessment according to RECIST 1.1. If a subject did not have an event, PFS was censored at the date of last adequate tumor assessment.~The PFS distribution was using the Kaplan-Meier method, and the Kaplan-Meier median and 95% confidence intervals of the medians was presented." (NCT04899349)
Timeframe: From the date of randomization to the date of the first documented progression or death due to any cause, whichever comes first, assessed up to a maximum duration of 7.4 months

Intervention	Months (Median)
Alpelisib + Fulvestrant + Dapagliflozin + Metformin XR	NA

Number of Participants With Dose Modifications

Number of participants with dose interruptions and dose reductions (NCT04899349)
Timeframe: From first dose of study medication up to 30 days after last dose of study medication, assessed up to 7.4 months

Intervention	Participants (Count of Participants)
	Dose interruptions	Dose reductions
Alpelisib + Fulvestrant + Dapagliflozin + Metformin XR	1	2
Alpelisib + Fulvestrant + Metformin XR	0	0

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability)

The frequency (and %) of patients who are reported as having grade 3-5 treatment-related adverse events were summarized. From starting the first dose of study treatment to 30 days (90 days for arm C) after last dose administration of study treatment or study discontinuation, whichever was earlier. Afterwards only SAEs attributed to study treatment were reported. (NCT03147287)
Timeframe: The median follow-up time for adverse event was 5.4 months (range 1.6 months to 51.2 months).

Intervention	Participants (Count of Participants)
Fulvestrant	1
Fulvestrant With Palbociclib	46
Fulvestrant With Palbociclib and Avelumab	37

Overall Response Rate, According to RECIST v1.1 Criteria (Investigator Assessment)

Objective Response (OR): best overall response of complete response or partial response. Response was primarily evaluated in this study using the criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). For example, target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions. See RECIST 1.1 manuscript for further details on overall assessment based on target lesions, non-target lesions and new lesions. The Overall Response Rate (with 2-sided 90% CIs) were estimated according to treatment assignment and subgroup. (NCT03147287)
Timeframe: Tumor were assessed every 8 weeks until 24 weeks, then every 12 weeks. The median follow-up time for overall response rate at database lock was 12.1 months (range 1 day to 50.1 months).

Intervention	percentage of participants analyzed (Number)
Fulvestrant	7.3
Fulvestrant With Palbociclib	9.0
Fulvestrant With Palbociclib and Avelumab	13.0

Progression-Free Survival (PFS), According to RECIST v1.1 Criteria (Investigator Assessment)

Progression-Free Survival (PFS), according to RECIST v1.1 criteria (investigator assessment): the time from randomization to the earlier of progression or death due to any cause. Participants alive without disease progression were censored at date of last disease assessment (tumor assessments). The date of progression was the first date that recurrent or progressive disease was objectively documented; if death was the defining event, it must have happened within 2 intervals of the last disease assessment, otherwise PFS was censored at last disease assessment. The length of PFS was calculated as PFS time (months) =[progression/death date(censor date) - randomization date + 1]/30.4375. (NCT03147287)
Timeframe: Tumor were assessed every 8 weeks until 24 weeks, then every 12 weeks. The median PFS follow-up time at database lock was 12.1 months (range 1 day to 50.1 months).

Intervention	months (Median)
Fulvestrant	4.8
Fulvestrant With Palbociclib	4.6
Fulvestrant With Palbociclib and Avelumab	8.1

Clinical Benefit Rate (CBR) Per Investigator Assessment

"CBR was defined as the percentage of participants with a best overall response of CR or PR or stable disease (SD) lasting 24 weeks or longer as defined in RECIST 1.1 as per investigator assessment.~CR: Disappearance of all lesions with lymph nodes measuring < 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.~SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease." (NCT02422615)
Timeframe: Up to approximately 26 months

Intervention	Percentage of participants (Number)
Ribociclib + Fulvestrant	70.2
Placebo + Fulvestrant	62.8

Duration of Response (DOR) Per Investigator Assessment

"DOR was defined as the time from the first documented response (CR or PR) to the first documented progression or death due to underlying cancer as defined in RECIST 1.1 per investigator assessment. The Kaplan-Meier method was used to estimate DOR, and the median DOR, along with 95% confidence intervals, was reported for each treatment group. If a participant had not had an event, duration was censored at the date of last adequate tumor assessment.~CR: Disappearance of all lesions with lymph nodes measuring < 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters." (NCT02422615)
Timeframe: From first documented response to progression or death, assessed up to approximately 26 months

Intervention	Months (Median)
Ribociclib + Fulvestrant	NA
Placebo + Fulvestrant	NA

Overall Response Rate (ORR) Per Investigator Assessment

"ORR was defined as the percentage of participants with the best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1 as per investigator assessment.~CR: Disappearance of all lesions with lymph nodes measuring < 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters." (NCT02422615)
Timeframe: Up to approximately 26 months

Intervention	Percentage of participants (Number)
Ribociclib + Fulvestrant	32.4
Placebo + Fulvestrant	21.5

Overall Survival (OS)

"OS was defined as the time from the date of randomization to the date of death from any cause. In cases where the patient's death was not recorded, the OS value was censored at the date of the last known patient's survival status. As per protocol, the final OS analysis was conducted after approximately 351 deaths were documented.~OS was estimated using the Kaplan-Meier method. The median OS, along with 95% confidence intervals (CIs), was reported for each treatment group.~The distribution of OS between the two treatment arms was compared using a log-rank test at one-sided cumulative 2.5% level of significance. A stratified Cox regression was used to estimate the OS hazard ratio and the associated 95% CI." (NCT02422615)
Timeframe: From randomization to death, assessed up to approximately 46 months

Intervention	Months (Median)
Ribociclib + Fulvestrant	NA
Placebo + Fulvestrant	40.0

Progression Free Survival (PFS) Per Blinded Independent Review Committee (BIRC)

"PFS was defined as the period starting from the date of randomization to the date of the first documented progression or death caused by any reason. In cases where patients did not experience an event, the PFS was censored at the date of the last adequate tumor assessment. Clinical deterioration without objective radiological evidence was not considered as documented disease progression.~PFS was assessed via BIRC assessment according to RECIST 1.1. The Kaplan-Meier method was used to estimate PFS, and the median PFS, along with 95% confidence intervals, was reported for each treatment group." (NCT02422615)
Timeframe: From randomization to first documented progression or death, assessed up to approximately 26 months

Intervention	Months (Median)
Ribociclib + Fulvestrant	NA
Placebo + Fulvestrant	10.9

Progression Free Survival (PFS) Per Investigator Assessment

"PFS was defined as the period starting from the date of randomization to the date of the first documented progression or death caused by any reason. In cases where patients did not experience an event, the PFS was censored at the date of the last adequate tumor assessment. Clinical deterioration without objective radiological evidence was not considered as documented disease progression.~PFS was assessed via local radiology assessment according to RECIST 1.1. The Kaplan-Meier method was used to estimate PFS, and the median PFS, along with 95% confidence intervals, was reported for each treatment group.~The distribution of PFS between the two arms was compared using a stratified log-rank test at a one-sided 2.5% level of significance. The PFS hazard ratio with two-sided 95% confidence interval was derived from the stratified Cox proportional hazards model." (NCT02422615)
Timeframe: From randomization to first documented progression or death, assessed up to approximately 26 months

Intervention	Months (Median)
Ribociclib + Fulvestrant	20.5
Placebo + Fulvestrant	12.8

Time to Definitive 10% Deterioration in the Global Health Status/Quality of Life (GHS/QoL) Scale Score of the European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30)

"The EORTC QLQ-C30 is a questionnaire that includes 5 functional scales, 3 symptom scales, a GHS/QoL scale, and 6 single items. GHS/QoL scale scores range between 0 and 100. A high score for GHS/QoL represents better functioning or QoL.~The time to definitive 10% deterioration is defined as the time from the date of randomization to the date of event, which is defined as at least 10% relative to baseline worsening of the QoL score (without further improvement above the threshold) or death due to any cause. The Kaplan-Meier method was used to estimate the distribution, and the median time to definitive 10% deterioration, along with 95% confidence intervals, was reported for each treatment group. If a patient had not had an event, time to deterioration was censored at the date of the last adequate QoL evaluation." (NCT02422615)
Timeframe: Up to approximately 26 months

Intervention	Months (Median)
Ribociclib + Fulvestrant	NA
Placebo + Fulvestrant	19.4

Time to Definitive Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG PS) in One Score Category

ECOG PS categorized patients based on their ability to perform daily activities and self-care, with scores ranging from 0 to 5. A score of 0 indicated no restrictions in activity, while higher scores indicated increasing limitations. Time to definitive deterioration was defined as the time from the date of randomization to the date of the event, defined as experiencing an increase in ECOG PS by at least one category from the baseline or death. A deterioration was considered definitive if no improvements in the ECOG PS were observed at a subsequent time. The Kaplan-Meier method was used to estimate the distribution, and the median time to definitive deterioration, along with 95% confidence intervals, was reported for each treatment group. Patients receiving any further therapy prior to definitive worsening were censored at their date of last assessment prior to start of therapy. Patients that had not worsened at the data cutoff point were censored at the date of last assessment. (NCT02422615)
Timeframe: Up to approximately 26 months

Intervention	Months (Median)
Ribociclib + Fulvestrant	NA
Placebo + Fulvestrant	NA

Time to Response (TTR) Per Investigator Assessment

"TTR was defined as the time from randomization to the first documented and confirmed response (CR or PR) as defined by RECIST 1.1 per investigator assessment. The Kaplan-Meier method was used to estimate TTR, and the median TTR, along with 95% confidence intervals, was reported for each treatment group. Participants who did not achieve a confirmed response were censored at the maximum follow-up time for patients who had a PFS event (i.e. either progressed or died due to any cause) or at the date of last adequate tumor assessment otherwise.~CR: Disappearance of all lesions with lymph nodes measuring < 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters." (NCT02422615)
Timeframe: From randomization to first response, assessed up to approximately 26 months

Intervention	Months (Median)
Ribociclib + Fulvestrant	NA
Placebo + Fulvestrant	NA

All Collected Deaths

"Pre-treatment deaths were collected from day of participant's informed consent to the day before first dose of study medication.~On-treatment deaths were collected from start of treatment to 30 days after last dose of treatment or one day before first administration of crossover treatment (for crossover participants), whichever came first Crossover on-treatment deaths were collected from start of crossover treatment up to 30 days after last dose of crossover treatment.~Post-treatment efficacy/survival follow-up deaths were collected from day 31 after last dose of study treatment to end of study.~Crossover post-treatment efficacy/survival follow-up deaths were collected from day 31 after last dose of crossover treatment to end of study." (NCT02422615)
Timeframe: Pre-treatment: Up to 28 days prior to treatment. On-treatment: Up to 82 months. Crossover on-treatment: Up to 3.5 months. Post-treatment efficacy/survival follow-up: Up to 82 months. Crossover post-treatment efficacy/survival follow-up: Up to 1 year

Intervention	Participants (Count of Participants)
	Pre-treatment deaths	On-treatment deaths	Post-treatment efficacy/survival deaths	All deaths
Ribociclib + Fulvestrant	0	13	264	277

All Collected Deaths

Intervention	Participants (Count of Participants)
	Pre-treatment deaths	On-treatment deaths	Crossover on-treatment deaths	Post-treatment efficacy/survival deaths	Crossover post-treatment efficacy/survival deaths	All deaths
Placebo + Fulvestrant	0	8	0	153	1	162

Change From Baseline in the GHS/QoL Scale Score of the EORTC QLQ-C30

"The EORTC QLQ-C30 is a questionnaire that includes 5 functional scales, 3 symptom scales, a GHS/QoL scale, and 6 single items. GHS/QoL scale scores range between 0 and 100. A high score for GHS/QoL represents better functioning or QoL.~The change from baseline in the GHS/QoL score was assessed. A positive change from baseline indicates improvement. For subjects who discontinued treatment without disease progression, post-treatment efficacy visits occurred every 8 weeks during the initial 18 months since start of treatment, followed by visits every 12 weeks until disease progression." (NCT02422615)
Timeframe: Baseline, every 8 weeks after randomization during 18 months, then every 12 weeks up to end of treatment; end of treatment; and every 8 or 12 weeks post-treatment until progression (post-treatment efficacy visits), assessed up to approximately 26 months

Intervention	Score on a Scale (Mean)
	Cycle 3 Day 1 (Cycle= 28 days)	Cycle 5 Day 1 (Cycle= 28 days)	Cycle 7 Day 1 (Cycle= 28 days)	Cycle 9 Day 1 (Cycle= 28 days)	Cycle 11 Day 1 (Cycle= 28 days)	Cycle 13 Day 1 (Cycle= 28 days)	Cycle 15 Day 1 (Cycle= 28 days)	Cycle 17 Day 1 (Cycle= 28 days)	Cycle 19 Day 1 (Cycle= 28 days)	Cycle 22 Day 1 (Cycle= 28 days)	Cycle 25 Day 1 (Cycle= 28 days)	Cycle 28 Day 1 (Cycle= 28 days)	End of treatment (EOT)	Post EOT1	Post EOT2	Post EOT3	Post EOT4
Placebo + Fulvestrant	2.7	3.2	4.3	3.3	2.3	1.3	3.6	3.4	3.7	4.7	8.3	19.4	-5.5	-33.3	-16.7	-16.7	-25.0

Change From Baseline in the GHS/QoL Scale Score of the EORTC QLQ-C30

"The EORTC QLQ-C30 is a questionnaire that includes 5 functional scales, 3 symptom scales, a GHS/QoL scale, and 6 single items. GHS/QoL scale scores range between 0 and 100. A high score for GHS/QoL represents better functioning or QoL.~The change from baseline in the GHS/QoL score was assessed. A positive change from baseline indicates improvement. For subjects who discontinued treatment without disease progression, post-treatment efficacy visits occurred every 8 weeks during the initial 18 months since start of treatment, followed by visits every 12 weeks until disease progression." (NCT02422615)
Timeframe: Baseline, every 8 weeks after randomization during 18 months, then every 12 weeks up to end of treatment; end of treatment; and every 8 or 12 weeks post-treatment until progression (post-treatment efficacy visits), assessed up to approximately 26 months

Intervention	Score on a Scale (Mean)
	Cycle 3 Day 1 (Cycle= 28 days)	Cycle 5 Day 1 (Cycle= 28 days)	Cycle 7 Day 1 (Cycle= 28 days)	Cycle 9 Day 1 (Cycle= 28 days)	Cycle 11 Day 1 (Cycle= 28 days)	Cycle 13 Day 1 (Cycle= 28 days)	Cycle 15 Day 1 (Cycle= 28 days)	Cycle 17 Day 1 (Cycle= 28 days)	Cycle 19 Day 1 (Cycle= 28 days)	Cycle 22 Day 1 (Cycle= 28 days)	Cycle 25 Day 1 (Cycle= 28 days)	Cycle 28 Day 1 (Cycle= 28 days)	End of treatment (EOT)	Post EOT1	Post EOT2	Post EOT3	Post EOT4	Post EOT5	Post EOT6	Post EOT7	Post EOT8	Post EOT9	Post EOT10
Ribociclib + Fulvestrant	4.5	4.2	4.9	4.1	4.9	4.4	3.6	3.9	3.8	6.6	5.7	12.5	-5.2	4.5	-4.8	14.6	10.0	13.9	22.2	19.4	37.5	8.3	-8.3

LEQ803 Plasma Concentrations

Blood samples were collected to assess the concentration by time point for LEQ803, a metabolite of ribociclib. Participants were classified into the following dose groups at each timepoint: 1) ribociclib 600 mg: consisted of all participants who provided evaluable concentrations after receiving at least 10 consecutive daily ribociclib doses of 600 mg immediately prior to the blood collection without a dose change or interruption. 2) ribociclib 400 mg: consisted of all participants who provided evaluable concentrations after receiving at least 10 consecutive daily ribociclib doses of 400 mg immediately prior to the blood collection without a dose change or interruption. 3) ribociclib 200 mg: consisted of all participants who provided evaluable concentrations after receiving at least 10 consecutive daily ribociclib doses of 200 mg immediately prior to the blood collection without a dose change or interruption. (NCT02422615)
Timeframe: Cycle 1 and Cycle 2 at Day 15 pre-dose and at 2, 4, and 6 hours post-dose. Cycle = 28 days

Intervention	ng/mL (Geometric Mean)
	Cycle 1 Day 15 predose (ribociclib 600 mg)	Cycle 1 Day 15 2 hours post-dose (ribociclib 600 mg)	Cycle 1 Day 15 4 hours post-dose (ribociclib 600 mg)	Cycle 1 Day 15 6 hours post-dose (ribociclib 600 mg)	Cycle 2 Day 15 predose (ribociclib 600 mg)	Cycle 2 Day 15 predose (ribociclib 400 mg)	Cycle 2 Day 15 2 hours post-dose (ribociclib 600 mg)	Cycle 2 Day 15 2 hours post-dose (ribociclib 400 mg)	Cycle 2 Day 15 2 hours post-dose (ribociclib 200 mg)	Cycle 2 Day 15 4 hours post-dose (ribociclib 600 mg)	Cycle 2 Day 15 4 hours post-dose (ribociclib 400 mg)	Cycle 2 Day 15 4 hours post-dose (ribociclib 200 mg)	Cycle 2 Day 15 6 hours post-dose (ribociclib 600 mg)	Cycle 2 Day 15 6 hours post-dose (ribociclib 400 mg)	Cycle 2 Day 15 6 hours post-dose (ribociclib 200 mg)
Ribociclib + Fulvestrant	75.6	134	137	128	72.7	46.2	126	70.8	36.0	134	79.3	41.9	122	72.3	38.3

Ribociclib Plasma Concentrations

Blood samples were collected to assess the concentration by time point for ribociclib. Participants were classified into the following dose groups at each timepoint: 1) ribociclib 600 mg: consisted of all participants who provided evaluable concentrations after receiving at least 10 consecutive daily ribociclib doses of 600 mg immediately prior to the blood collection without a dose change or interruption. 2) ribociclib 400 mg: consisted of all participants who provided evaluable concentrations after receiving at least 10 consecutive daily ribociclib doses of 400 mg immediately prior to the blood collection without a dose change or interruption. 3) ribociclib 200 mg: consisted of all participants who provided evaluable concentrations after receiving at least 10 consecutive daily ribociclib doses of 200 mg immediately prior to the blood collection without a dose change or interruption. (NCT02422615)
Timeframe: Cycle 1 and Cycle 2 at Day 15 pre-dose and at 2, 4, and 6 hours post-dose. Cycle=28 days

Intervention	nanogram (ng) / miliLiter (mL) (Geometric Mean)
	Cycle 1 Day 15 predose (ribociclib 600 mg)	Cycle 1 Day 15 2 hours post-dose (ribociclib 600 mg)	Cycle 1 Day 15 4 hours post-dose (ribociclib 600 mg)	Cycle 1 Day 15 6 hours post-dose (ribociclib 600 mg)	Cycle 2 Day 15 predose (ribociclib 600 mg)	Cycle 2 Day 15 predose (ribociclib 400 mg)	Cycle 2 Day 15 2 hours post-dose (ribociclib 600 mg)	Cycle 2 Day 15 2 hours post-dose (ribociclib 400 mg)	Cycle 2 Day 15 2 hours post-dose (ribociclib 200 mg)	Cycle 2 Day 15 4 hours post-dose (ribociclib 600 mg)	Cycle 2 Day 15 4 hours post-dose (ribociclib 400 mg)	Cycle 2 Day 15 4 hours post-dose (ribociclib 200 mg)	Cycle 2 Day 15 6 hours post-dose (ribociclib 600 mg)	Cycle 2 Day 15 6 hours post-dose (ribociclib 400 mg)	Cycle 2 Day 15 6 hours post-dose (ribociclib 200 mg)
Ribociclib + Fulvestrant	627	1670	1690	1420	553	220	1470	794	104	1610	913	112	1280	710	104

Change From Randomisation in Trial Outcome Index (TOI) Over the Course of the Study

Mean (and standard deviation) change from randomisation until treatment discontinuation in TOI (defined as the first visit response of 'worsened' which is a decrease in TOI from baseline of 5 points or more) using the Kaplan-Meier method. If a subject has not shown a reduction of 5 points or more at the time of analysis then the observation will be right censored using the last QOL assessment date. Trial Outcome Index (TOI) is derived from the FACT-B questionnaire (Cella et al, 1993) by adding together the scores from the following 3 subscales; Physical well-being (PWB), Functional well-being (FWB) and Breast cancer subscale (BCS). The TOI score range is 0-92 with the higher scores representing the more favourable outcomes. Data were collected from a subgroup of patients. (NCT00099437)
Timeframe: TOI questionnaires were completed every 4 weeks from randomisation until week 24 and then again at treatment discontinuation, for study duration (48 months)

Intervention	Scores on a scale (Mean)
Fulvestrant 250 mg	-5.9
Fulvestrant 500 mg	-7.5

Clinical Benefit Rate (CBR)

A Clinical Benefit (CB) responder is defined as a patient having a best overall response of CR, PR or SD (stable disease) >=24 weeks. The Clinical Benefit Rate is the percentage of patients with CB. (NCT00099437)
Timeframe: Clinical Benefit from the sequence of RECIST scan data for study duration (48 months) . RECIST (Response Evaluation Criteria in Solid Tumours) scans were performed every 12 weeks (+/- 2 weeks) from randomisation for study duration (48 months)

Intervention	Percentage of patients (Number)
Fulvestrant 250 mg	39.6
Fulvestrant 500 mg	45.6

Duration of Clinical Benefit (DoCB)

Time from randomisation until objective progression or death (in the absence of objective progression), measured only in those patients who achieve a confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) >=24 weeks (NCT00099437)
Timeframe: RECIST tumour assessments carried out every 12 weeks (+/- 2 weeks) from randomisation for study duration (48 months)

Intervention	Time (in months) (Median)
Fulvestrant 250 mg	13.9
Fulvestrant 500 mg	16.6

Duration of Response (DoR)

Time from randomisation until objective progression or death (in the absence of objective progression), measured only in those patients who achieve a confirmed complete response (CR) or confirmed partial response (PR) (NCT00099437)
Timeframe: RECIST tumour assessments carried out every 12 weeks (+/- 2 weeks) from randomisation for study duration (48 months)

Intervention	Time (in months) (Median)
Fulvestrant 250 mg	16.4
Fulvestrant 500 mg	19.4

Objective Response Rate (ORR)

Using the RECIST scan data, an objective response (OR) is defined as a patient having a best overall response of either complete response (CR) or partial response (PR) which is subsequently confirmed as per RECIST. ORR is defined as the percentage of patients with OR. (NCT00099437)
Timeframe: RECIST tumour assessments carried out every 12 weeks (+/- 2 weeks) from randomisation for study duration (48 months)

Intervention	Percentage of patients (Number)
Fulvestrant 250 mg	14.6
Fulvestrant 500 mg	13.8

Overall Survival (OS) - Follow-up

Overall Survival is equivalent to time to death. For this endpoint, all deaths occurring during the study as a whole until the data cut-off for the survival extension (31st October 2011) are presented (analysis at 75% deaths) (NCT00099437)
Timeframe: Median time (in months) from randomisation until death (from any cause),up to 80 months

Intervention	months (Median)
Fulvestrant 250 mg	22.3
Fulvestrant 500 mg	26.4

Overall Survival (OS)

Median time (in months) from randomisation until death (from any cause) (analysis at 50% deaths ) (NCT00099437)
Timeframe: Overall Survival is equivalent to time to death. For this endpoint, all deaths occurring for study duration (48 months)

Intervention	Time (in months) (Median)
Fulvestrant 250 mg	22.8
Fulvestrant 500 mg	25.1

Time to Progression (TTP)

Median time (in months) from randomisation until objective disease progression or death (in the absence of objective progression). (NCT00099437)
Timeframe: RECIST(Response Evaluation Criteria in Solid Tumors ) tumour assessments carried out every 12 weeks (+/- 2 weeks) from randomisation for study duration (48 months)

Intervention	months (Median)
Fulvestrant 250 mg	5.5
Fulvestrant 500 mg	6.5

Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Health Utility Index Value

EQ-5D-5L: consists of 2 sections: EQ-5D-5L health state utility index (descriptive system) & VAS. The EQ-5D descriptive system consists of 5 dimensions: mobility, self-care, usual activities, pain/discomfort & anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, & extreme problems. Response options are measured with 5-point Likert scale (for 5L version). The EQ-5D-5L responses are converted into single index utility score between 0 to 1, where higher score indicates better health state & lower score indicate worse health state. LS mean and SE are derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from baseline values overall treatment (i.e., each cycle [Cycle 1 up to Cycle 30]) was reported in this outcome measure. (NCT04059484)
Timeframe: Baseline, overall treatment duration (Cycle 1 up to Cycle 30 [i.e.,116 weeks])

Intervention	score on a scale (Least Squares Mean)
Physician Choice Endocrine Monotherapy (PCEM)	-0.0
Amcenestrant	-0.0

Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Visual Analog Scale (VAS) Score

EQ-5D-5L is a standardized measure of health status, provides a simple, generic measure of health for clinical and economic appraisal, and consists of 2 sections: the EQ-5D-5L health state utility index (descriptive system) and the EQ-5D-5L VAS. The Visual Analogue Scale is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. LS mean and SE are derived from MMRM model with change from baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from Baseline values of overall treatment (i.e., each cycle [Cycle 1 up to Cycle 30]) was reported in this outcome measure. (NCT04059484)
Timeframe: Baseline, overall treatment duration (Cycle 1 up to Cycle 30 [i.e.,116 weeks])

Intervention	score on a scale (Least Squares Mean)
Physician Choice Endocrine Monotherapy (PCEM)	0.9
Amcenestrant	0.2

Duration of Response (DOR)

DOR is defined as time (in months) from first documented evidence of CR or PR until progressive disease (PD) determined by ICR as per RECIST 1.1 or death from any cause, whichever occurs first. For participants with ongoing response at the time of the analysis, DOR was censored at the date of the last valid disease assessment not showing documented progression performed before the initiation of a new anticancer treatment (if any). As per RECIST 1.1, CR: disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. (NCT04059484)
Timeframe: From the date of first response to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (maximum duration: 116 weeks)

Intervention	months (Median)
Physician Choice Endocrine Monotherapy (PCEM)	NA
Amcenestrant	15.1

Overall Survival (OS)

OS is defined as the time interval from the date of randomization to the date of documented death (due to any cause). In the absence of observation of death, survival time was censored to last date the participant is known to be alive or at the cut-off date, whichever comes first. Analysis was performed by Kaplan-Meier method. (NCT04059484)
Timeframe: From randomization to the death due to any cause or data cut-off date whichever comes first (maximum duration: 116 weeks)

Intervention	months (Median)
Physician Choice Endocrine Monotherapy (PCEM)	NA
Amcenestrant	NA

Percentage of Participants With Clinical Benefit

Clinical Benefit is defined as percentage of participants having a confirmed CR, PR, SD, or Non-CR/Non-PD for at least 24 weeks determined by ICR as per RECIST 1.1 from the date of randomization to the date of end of treatment. As per RECIST 1.1, CR: disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters. Non-CR/Non-PD: persistence of one or more nontarget lesion(s) and/or maintenance of tumor marker level above the normal limits. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. (NCT04059484)
Timeframe: From randomization to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (maximum duration: 116 weeks)

Intervention	percentage of participants (Number)
Physician Choice Endocrine Monotherapy (PCEM)	29.3
Amcenestrant	27.3

Percentage of Participants With Disease Control

Disease control is defined as percentage of participants having a confirmed CR, PR, or stable disease (SD) or Non-CR/Non-PD as BOR determined by ICR as per RECIST 1.1 from the date of randomization to the date of end of treatment. As per RECIST 1.1, CR: disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters. Non-CR/Non-PD: persistence of one or more nontarget lesion(s) and/or maintenance of tumor marker level above the normal limits. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. (NCT04059484)
Timeframe: From randomization to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (maximum duration: 116 weeks)

Intervention	percentage of participants (Number)
Physician Choice Endocrine Monotherapy (PCEM)	53.7
Amcenestrant	54.5

Percentage of Participants With Objective Response

Objective response is defined as percentage of participants having a partial response (PR) or complete response (CR) according to the RECIST version 1.1 assessed by ICR. As per RECIST 1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. (NCT04059484)
Timeframe: From randomization to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (maximum duration: 116 weeks)

Intervention	percentage of participants (Number)
Physician Choice Endocrine Monotherapy (PCEM)	8.8
Amcenestrant	11.9

Progression Free Survival (PFS)

PFS is defined as the time in months interval from the date of randomization to the date of first documented tumor progression as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) assessed by independent central review (ICR) or death (due to any cause), whichever comes first. Progressive Disease (PD) as per RECIST 1.1: at least a 20 percent (%) increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method. (NCT04059484)
Timeframe: From randomization to the date of first documented tumor progression or death due to any cause or data cut-off date whichever comes first (maximum duration: 116 weeks)

Intervention	months (Median)
Physician Choice Endocrine Monotherapy (PCEM)	3.7
Amcenestrant	3.6

Within-Participant Steady State Ctrough of Amcenestrant

Within-participant Steady state Ctrough was defined as the median value of the Ctrough across study using plasma concentration of predose samples at Cycle 1 Day 15 and Day 1 of Cycle 2, 3, 4 and 6 for each individual participant. Average (mean) of all calculated Ctrough values for all participants across study (Cycle 1 Day 15 and Day 1 of Cycle 2, 3, 4 and 6 ) was derived and reported in this outcome measure. (NCT04059484)
Timeframe: Predose on Cycle 1 Day 15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 4 Day 1; Cycle 6 Day 1

Intervention	ng/mL (Mean)
Amcenestrant	491.35

Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30) Domain Scores

EORTC-QLQ-C30: cancer-specific instrument with 30 questions for evaluation of new chemotherapy & assessment of participant reported outcome. These include 5 functional scales, 9 symptom scales, & Global Health Status/quality of life scale (GHS/QoL). All 14 items/domains were scored on scale of 1 (not at all) to 4 (very much) and GHS/QoL, scored on scale of 1 (very poor) to 7 (excellent). All scales are transformed from raw scores to linear scales ranging 0 to 100. Higher score for functional & GHS/QoL = higher level of functioning, & higher score for symptoms scales = higher symptom burden. Least Square (LS) mean and Standard Error (SE) are derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from baseline values of overall treatment (i.e., each cycle [Cycle 1 up to Cycle 30]) was reported in this outcome measure. (NCT04059484)
Timeframe: Baseline, overall treatment duration (Cycle 1 up to Cycle 30 [i.e.,116 weeks])

Intervention	score on a scale (Least Squares Mean)
	GHS/QoL	Physical functioning	Role functioning	Emotional functioning	Cognitive functioning	Social functioning	Fatigue	Nausea and vomiting	Pain	Dyspnoea	Insomnia	Appetite loss	Constipation	Diarrhoea	Financial difficulties
Amcenestrant	2.5	-3.1	-3.0	3.0	-0.8	-0.8	2.8	1.3	2.1	0.8	-2.3	1.2	3.0	3.9	-2.0
Physician Choice Endocrine Monotherapy (PCEM)	1.8	-1.2	-2.4	-2.2	-0.9	-2.5	1.1	1.7	1.1	1.0	-1.1	2.4	-2.3	0.3	1.7

Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Breast Cancer Specific Module (EORTC-QLQ-BR23) Domain Scores

QLQ-BR23: disease-specific Health-related QOL assesses impact of breast cancer & side effects of treatment. EORTC-QLQ-BR23 contains 23 items: multi-item scales & single-item measures. 4 functional scales (body image, sexual functioning, sexual enjoyment, future perspective) & 4 scales related to symptoms of disease or treatment (arm symptoms, breast symptoms, systemic therapy side effects, & upset by hair loss). All items scored 1 (not at all) to 4 (very much). Scores of all scales transformed from raw scores to linear scales ranging 0 to 100. Higher score for functional scales = better outcome; higher score for symptoms scales = higher symptom burden. LS mean and SE are derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from baseline values of overall treatment (i.e., each cycle [Cycle 1 up to Cycle 30]) was reported. (NCT04059484)
Timeframe: Baseline, overall treatment duration (Cycle 1 up to Cycle 30 [i.e.,116 weeks])

Intervention	score on a scale (Least Squares Mean)
	Body image	Sexual functioning	Sexual enjoyment	Future perspective	Systemic therapy side effects	Breast symptoms	Arm symptoms	Upset by hair loss
Amcenestrant	2.2	-2.6	0.4	12.0	0.7	-0.8	2.0	-10.6
Physician Choice Endocrine Monotherapy (PCEM)	1.8	-2.4	-1.1	10.6	0.2	-0.4	1.8	-9.7

Pharmacokinetics: Plasma Concentrations of Amcenestrant

Amcenestrant plasma concentrations at specified time points are reported. (NCT04059484)
Timeframe: Cycle 1 Day 1: 1.5 hours(h), 4h post-dose, Day 15: pre-dose, Cycle 2 Day 1: pre-dose, 1.5h, 4h, 8h post-dose, Cycle 3 Day 1: pre-dose, Cycle 4 Day 1: pre-dose, Cycle 6 Day 1: pre-dose

Intervention	nanograms per milliliter (ng/mL) (Mean)
	Cycle 1 Day 1: 1.5h	Cycle 1 Day 1: 4h	Cycle 1 Day 15: Pre-dose	Cycle 2 Day 1: Pre-dose	Cycle 2 Day 1: 1.5h	Cycle 2 Day 1: 4h	Cycle 2 Day 1: 8h	Cycle 3 Day 1: Pre-dose	Cycle 4 Day 1: Pre-dose	Cycle 6 Day 1: Pre-dose
Amcenestrant	3185.7	4753.1	516.4	479.1	2719.6	3801.8	2303.8	593.6	661.5	531.5

Progression Free Survival (PFS) According to Estrogen Receptor 1 Gene (ESR1) Mutation Status

PFS defined as the time (in months) interval from the date of randomization to the date of first documented tumor progression as per RECIST 1.1 assessed by ICR or death (due to any cause), whichever comes first. Progression as per RECIST 1.1: at least a 20 percent (%) increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. The mutation status (wild type, mutant) of twelve specific mutations of the ESR1 gene was determined by multiplex droplet digital polymerase chain reaction (ddPCR), including their mutant frequency and concentration. Here, PFS is reported based on the ESR1 mutation status of participants: wild type and mutants. ESR1 was the gene encoding estrogen receptor alpha. ESR1 mutant type breast cancer was a disease where the ESR1 gene had a mutation (i.e., a type of error). ESR1 wild type breast cancer was a disease where the ESR1 gene was normal without a mutation. Analysis was performed by Kaplan-Meier method. (NCT04059484)
Timeframe: From randomization to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (maximum duration: 116 weeks)

Intervention	months (Median)
	Mutated	Wild type
Amcenestrant	3.7	3.5
Physician Choice Endocrine Monotherapy (PCEM)	2.0	3.9

Change in Ki-67 Levels From Baseline (Pre) to Day 28 (Post) Biopsy Samples

The primary endpoint is change in Ki-67 levels from baseline (pre) to day 28 (post) biopsy samples. Ki-67 levels were log-transformed to achieve approximately normally distributed data. The differences in these log-transformed values between post vs. pre biopsy samples were calculated. This difference represents the log of the ratio of post vs. pre Ki-67 levels in the original scale. (NCT00570323)
Timeframe: baseline (pre) to day 28 (post)

Intervention	log-transformed Ki67% (Mean)
ARM A / Arimidex With Faslodex	-1.3632
ARM B Arimidex Without Faslodex	-1.6237

Androgen Receptor (AR) Expression

The strength of AR signaling was measured by the percentage of downstream AR-regulated genes that were expressed. (NCT02955394)
Timeframe: 16 Weeks

Intervention	percentage of genes expressed (Median)
Fulvestrant Without Enzalutamide	85
Fulvestrant With Enzalutamide	80

Disease-free Survival

Disease-free survival is defined as the time in months from the start of fulvestrant until documented disease progression or death. Complete and partial response for the single drug arm and combination of enzalutamide/fulvestrant arm separately. (NCT02955394)
Timeframe: 15 months

Intervention	months (Median)
Fulvestrant Without Enzalutamide	3.6
Fulvestrant With Enzalutamide	3.7

Number of Patients With a PEPI Score Equal to Zero at Post Treatment

"The preoperative endocrine prognostic index (PEPI) is a validated measure of pathologic response to endocrine therapy. It is a model that combines estrogen receptor (ER) level, pathologic tumor site, nodal status, and Ki67 score at the time of surgery to predict subsequent risk of cancer recurrence.~PEPI scoring is typically discretized into three risk groups: 0 (low risk of recurrence and best outcome), 1-3 (intermediate risk), and >= 4 (high risk). This study was concerned only with the distinction between zero and non-zero PEPI scores. Zero is the minimum score, and there is no maximum score. Lower scores are better." (NCT02955394)
Timeframe: 16 Weeks

Intervention	Participants (Count of Participants)
Fulvestrant Without Enzalutamide	2
Fulvestrant With Enzalutamide	8

Overall Survival in All Subjects

Overall Survival in All (ESR1-mut and ESR1-WT) Subjects (NCT03778931)
Timeframe: From Date of Randomization until Death Due to Any Cause (Estimated up to 24 Months)

Intervention	months (Median)
Elacestrant	NA
Standard of Care (SoC)	NA

Overall Survival in ESR1-mut Subjects

Overall Survival in ESR1-mut subjects, where Overall Survival is defined as the length of time from randomization until the date of death from any cause (NCT03778931)
Timeframe: From Date of Randomization until Death Due to Any Cause (Estimated up to 24 Months)

Intervention	months (Median)
Elacestrant	NA
Standard of Care (SoC)	16.95

Progression-free Survival in All Subjects

Progression-free Survival based on blinded Imaging Review Committee (IRC) assessment in all (ESR1-mut and ESR1-WT) subjects (NCT03778931)
Timeframe: From Date of Randomization until Disease Progression or Death Due to Any Cause (up to 12 Months)

Intervention	months (Median)
Elacestrant	2.79
Standard of Care (SoC)	1.91

Progression-free Survival in ESR1-mut Subjects

Progression-free Survival based on blinded IRC assessment in ESR1-mut subjects defined as the length of time from randomization until the date of objective disease progression per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as assessed by the blinded IRC or death from any cause. Progression is defined per RECIST v1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT03778931)
Timeframe: From Date of Randomization until Disease Progression or Death Due to Any Cause (up to 12 Months)

Intervention	months (Median)
Elacestrant	3.78
Standard of Care (SoC)	1.87

12-Month Survival Rate

The 12-month survival rate is defined as the percentage of participants who have not died 12 months after the date of randomization. (NCT00728949)
Timeframe: From randomization to until the date of first documented date of death from any cause within 12 months, assessed up to 35.1 months

Intervention	percentage of participants (Number)
IMC-A12 (Cixutumumab) + Antiestrogen Therapy	15
IMC-A12 (Cixutumumab)	7.6

Overall Survival (OS)

OS is defined as the interval between date of randomization and the date of death due to any cause. Participants who are alive at the time of study completion will be censored at the time the participants was last known to be alive. (NCT00728949)
Timeframe: From randomization up to 36.5 Months

Intervention	months (Median)
IMC-A12 (Cixutumumab) + Antiestrogen Therapy	20.3
IMC-A12 (Cixutumumab)	NA

Percentage of Participants With Complete Response (CR) and Partial Response (PR) (Objective Response Rate [ORR])

Best overall response of CR or PR was defined using RECIST v 1.0 criteria. CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker levels of non-target lesions. PR was defined as ≥30% decrease in sum of longest diameter (SOD) of target lesions taking as reference the baseline sum diameter. PD was defined as ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR/total number of participants)*100. (NCT00728949)
Timeframe: Randomization to PD up to 35.1 Months

Intervention	percentage of participants (Number)
IMC-A12 (Cixutumumab) + Antiestrogen Therapy	1.6
IMC-A12 (Cixutumumab)	0

Percentage of Participants With Complete Response (CR) and Partial Response (PR) or Stable Disease (SD) Disease Control Rate [DCR])

DCR is defined as percentage of participants with CR, PR, or SD using RECIST v 1.0 criteria. CR: disappearance of all lesions, pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker levels of non-target lesions. PR: ≥30% decrease in SOD of target lesions taking as reference baseline sum diameter. PD: ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference smallest sum of longest diameters recorded since treatment started and an absolute increase in sum diameter ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. SD: neither sufficient shrinkage to qualify for PR nor increase to qualify for PD. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR+SD/total number of participants)*100. (NCT00728949)
Timeframe: Randomization to PD up to 35.1 Months

Intervention	percentage of participants (Number)
IMC-A12 (Cixutumumab) + Antiestrogen Therapy	40.3
IMC-A12 (Cixutumumab)	51.6

Progression-Free Survival (PFS)

PFS is defined as the time from the date of randomization until date of objectively determined progressive disease (PD) or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a ≥20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions unequivocal progression of non-target lesions. Participants without documentation of progression or death will be censored at the date of last tumor assessment. The PFS will be estimated following the Kaplan-Meier method. (NCT00728949)
Timeframe: From randomization up to 35.1 Months

Intervention	months (Median)
IMC-A12 (Cixutumumab) + Antiestrogen Therapy	2.0
IMC-A12 (Cixutumumab)	3.1

Number of Participants Experiencing Adverse Events (AEs) in National Cancer Institute Common Toxicity Criteria for AE's (NCI-CTCAE) Version 3.0 Criteria for Adverse Events (NCI-CTCAE)

The NCI-CTCAE provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided for each adverse event term. Severity will be graded as mild (grade 1), moderate (grade 2), severe (grade 3), or very severe (life threatening - grade 4). Clinically significant events were defined as serious and other non-serious adverse events related to study drug regardless of causality. A summary of serious and other non-serious adverse events is located in the Reported Adverse Event module. (NCT00728949)
Timeframe: Randomization to End of Study up to 36.5 Months

Intervention	Participants (Count of Participants)
	Participants with any AE	Participants with SAE's	AE of greater than Grade 3	AE with outcome of Death	Study drug-related AE	Study drug-related SAE's	Study drug-related AE of greater than Grade 3	AE leading to discontinuation of any study drug
IMC-A12 (Cixutumumab)	36	11	19	2	31	2	7	1
IMC-A12 (Cixutumumab) + Antiestrogen Therapy	55	16	22	3	48	5	10	6

Duration of Clinical Benefit

The duration of clinical benefit was measured from the time of clinical benefit of CR, PR or SD to the time of progressive disease or death from any cause. PD was defined as having at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase above nadir. Kaplan-Meier (KM) techniques were used to assess the time-to-event endpoints. (NCT00451555)
Timeframe: Time of Clinical Benefit to Progressive Disease or Death (Up to 3 Years)

Intervention	months (Median)
Enzastaurin + Fulvestrant BID + QD	9.6
Enzastaurin + Fulvestrant BID	9.4
Enzastaurin + Fulvestrant QD	9.6
Placebo + Fulvestrant BID	9.7

Percentage of Participants Achieving Overall Tumor Response Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR])

The ORR is equal to the percentage of participants achieving a best overall response of partial response or complete response (PR + CR), according to RECIST version 1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes must have reduction in short axis to <10 millimeter (mm) and normalization of tumor marker level of non-target lesions; PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions; PD was defined as having at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase above nadir; SD was defined as small changes that did not meet above criteria. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. The 95% confidence interval (CI) was calculated by exact method. Kaplan-Meier (KM) techniques were used to assess the time-to-event endpoints. (NCT00451555)
Timeframe: Baseline to Measured Progressive Disease or Study Discontinuation (Up to 24 Weeks)

Intervention	percentage of participants (Number)
Enzastaurin + Fulvestrant QD + BID	5.3
Enzastaurin + Fulvestrant BID	5.1
Enzastaurin + Fulvestrant QD	5.5
Fulvestrant + Placebo	5.2

Percentage of Participants Who Achieved a Best Response of Complete Response, Partial Response, and Stable Disease (CR+PR+SD) (Clinical Benefit Rate)

Clinical benefit rate is defined as the rate of confirmed CR, confirmed PR, and SD for 24 weeks duration and is the best response CR, PR, or SD as classified by the investigators according to the RECIST v1.1. CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of not-target lesions or appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameter since treatment started. Kaplan-Meier (KM) techniques were used to assess the time-to-event endpoints. Progressive Disease (PD) was defined as having at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase above nadir. (NCT00451555)
Timeframe: Baseline to Measured Progressive Disease or Study Discontinuation (Up to 24 Weeks)

Intervention	percentage of participants (Number)
Enzastaurin + Fulvestrant QD + BID	43.6
Enzastaurin + Fulvestrant BID	43.6
Enzastaurin + Fulvestrant QD	43.6
Fulvestrant + Placebo	44.8

Progression Free Survival (PFS)

Progression-free survival (PFS) time was defined as the time from baseline to the first date of progressive disease (symptomatic or objective) or death due to any cause, whichever occurred first. PD was defined as having at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase above nadir.For participants who were not known to have died or progressed as of the data-inclusion cutoff date, PFS time was censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent systematic anticancer therapy. PFS was summarized using Kaplan-Meier estimates. (NCT00451555)
Timeframe: Baseline to Measured Progressive Disease or Death Due to Any Cause (Up to 3 Years)

Intervention	months (Median)
Enzastaurin + Fulvestrant QD + BID	5.2
Enzastaurin + Fulvestrant BID	3.7
Enzastaurin + Fulvestrant QD	6.0
Fulvestrant + Placebo	5.5

Number of Participants Who Discontinued With Adverse Events (AE) and Serious Adverse Events (SAEs)

Clinically significant events were defined as serious AEs (SAEs) and other non-serious AEs, regardless of causality. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. Participants who discontinued due to an AE or SAE are reported. (NCT00451555)
Timeframe: From Baseline to Study Completion (Up to 3 years, 9 months)

,,,

Intervention	Participants (Count of Participants)
	Adverse Events (AEs)	Serious Adverse Events (SAEs)
Enzastaurin + Fulvestrant BID	1	0
Enzastaurin + Fulvestrant QD	2	0
Enzastaurin + Fulvestrant QD + BID	3	0
Fulvestrant + Placebo	1	1

Safety and Tolerability of Two Delivery Methods

Number of adverse events per CTCAE v4.0 after treatment with fulvestrant by route of administration (NCT02540330)
Timeframe: Up to 4 weeks

Intervention	Participants (Count of Participants)
Intramuscular Route	1
Intraductal Route	0

Safety and Tolerability in Terms of Number of Patients With Adverse Events (Serious and Non-serious)

(NCT01202591)
Timeframe: 3 years, 10 months (Adverse events recorded from patient screening to discontinuation plus 28 days safety follow-up).

Intervention	Participants (Number)
AZD4547 80mg bd Cont + Ex 25mg	5
AZD4547 40mg Cont + Ex 25mg	5
AZD4547 80mg bd 1w/1w + Ex 25mg	12
AZD4547 80mg bd 2w/1w + Ex 25mg	9
Part B: AZD4547 + Fulvestrant	5
Part B: Placebo + Fulvestrant	2

Clinical Benefit Rate

Clinical benefit rate is defined as a complete response, partial response, or stable disease (CR, PR, SD) by Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for a minimum of at least 24 weeks or more. (NCT00570921)
Timeframe: Duration of response or stable disease for 24 weeks or more

Intervention	participants (Number)
Fulvestrant + Everolimus	15

Objective Response Rates

Intervention	participants (Number)
Fulvestrant + Everolimus	4

Time to Progression

(NCT00570921)
Timeframe: Duration of time start of treatment to time of documented progression or death

Intervention	months (Median)
Fulvestrant + Everolimus	7.4

Percentage of Participants Experiencing at Least One Treatment-Emergent Adverse Event

Treatment-emergent adverse events (TEAEs) are defined as any adverse events that started at the time of, or after the, first study medication administration as well as those events that started prior to the first study drug administration, but which worsened after the first study medication administration. The reported data reflects the unique percentage of participants who experienced any serious and other non-serious adverse events. A summary of serious and other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module. (NCT04707196)
Timeframe: Baseline until end of follow-up (Up To 7 Months)

Intervention	percentage of participants (Number)
Abemaciclib + NSAI	78.1
Abemaciclib + Fulvestrant	69.8

Percentage of Participants Who Discontinued From Study Treatment Due to Adverse Events

An adverse event is any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. (NCT04707196)
Timeframe: Baseline until end of study treatment (Up To 6 Months)

Intervention	percentage of participants (Number)
Abemaciclib + NSAI	3.6
Abemaciclib + Fulvestrant	4.8

Clinical Benefit Rate (CBR) of Adding Bortezomib to Fulvestrant in Arm C

This outcome measure determined if the addition of bortezomib to fulvestrant improved the clinical benefit rate (defined as objective response plus stable disease for at least 24 weeks from day+1). Clinical Benefit Rate (CBR) is defined as the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease to a therapeutic intervention in clinical trials of anticancer agents. (NCT01142401)
Timeframe: Up to 24 weeks

Intervention	Participants (Count of Participants)
Arm C: Crossover From Arm A at Progression to Fulvestrant + Bortezomib	5

Number of Participants Who Survived Until Study End (up to 7 Years)

Tabulation of the number of participants who survived from the date of first treatment until study end (up to 7 years). (NCT01142401)
Timeframe: From first treatment day until study end, assessed up to 7 years

Intervention	Participants (Count of Participants)
Arm A: Fulvestrant Alone	39
Arm B: Fulvestrant + Bortezomib	42

Number of Participants With Progression Free Survival (PFS) at 12 Months

The number of patients, treated with fulvestrant alone and fulvestrant plus bortezomib, who remained progression-free (Arms A vs. B). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions (NCT01142401)
Timeframe: At 12 months

Intervention	Participants (Count of Participants)
Arm A: Fulvestrant	8
Arm B: Fulvestrant + Bortezomib	16

Number of Participants With Progression Free Survival (PFS) at 6 Months

(NCT01142401)
Timeframe: At 6 months

Intervention	Participants (Count of Participants)
Arm A: Fulvestrant	16
Arm B: Fulvestrant + Bortezomib	22

Progression Free Survival at 24 Weeks (Arm C)

(NCT01142401)
Timeframe: At 24 weeks

Intervention	Participants (Count of Participants)
Arm C: Crossover From Arm A at Progression to Fulvestrant + Bortezomib	5

Frequency of Most Common Toxicities

Most common toxicities in the fulvestrant arm alone (Arm A) and the fulvestrant/bortezomib combination arm (Arm B). Most common toxicities are defined as adverse events having occurred in >10% of the participants within either (or both) Arm A or Arm B. (NCT01142401)
Timeframe: Up to 7 years

Intervention	percentage of participants (Number)
	Hemoglobin-Low	White Blood Cell-Low	Hyperglycemia/Glucose-High	Hypoglycemia/Glucose-Low	SGOT (AST-High)	SGPT (ALT-High)	Neutrophil Count Decreased/ANC-low	Platelet Count Decreased/Platelets-Low	Hypocalcemia/Calcium-Low	Hyponatremia/Sodium-Low	Nausea	Vomiting	Diarrhea	Constipation	Heartburn/Dyspepsia	Anorexia	Headache	Pain (general)	Peripheral Neuropathy (Motor, Pain, Sensory)	Injection Site Reaction	Dyspnea	Cough	Fatigue	Limb Edema	Insomnia	Hot Flashes	Dizziness	Arthralgia	Myalgia	Anxiety	Fever	Pruritis	Rash/Desquamation	Depression	Anemia	Dry Eye	Hypertension	Rash (General)	Eye Disorders (not otherwise specified)	Urinary Disorders (General)	Thrombocytopenia	Neutropenia	Upper Respiratory Disorders (General)	Musculoskeletal Pain Disorders (not otherwise specified)	Mucositis Oral
Arm A: Fulvestrant	41	32	44	5	25	14	10	8	10	8	29	14	8	34	10	15	12	59	31	24	32	29	56	19	25	37	7	36	10	8	15	7	8	8	32	0	12	7	7	15	41	8	12	17	8
Arm B: Fulvestrant + Bortezomib	61	42	51	12	32	21	12	30	12	12	63	32	47	46	18	23	25	54	49	12	19	23	56	37	35	32	19	28	18	19	12	16	11	16	42	12	21	23	12	11	61	30	23	18	11

Mean Baseline GH Concentration

Averaged over 90-min baseline on the saline day. (NCT01186796)
Timeframe: Withdrawal of blood samples (2.5 mL each) every 10 min for 6 hr. Sampling will begin at 0800 h and conclude at 1400 h.

Intervention	ug/L (Mean)
Fulvestrant Group	0.23
Saline Placebo Group	0.096

Mean Duration of GH Bursts (Mode) in Response to Secretagogue

Subjects were administered 4 different secretagogues: (i) L-arginine/Saline, (ii) L-arginine/Ghrelin, (iii) L-arginine/GHRH, and (iv) L-arginine / GHRH + Ghrelin. The result was calculated on each 6-hr pool of data by utilizing a previously published deconvolution method and analyzed via two-way ANOVA. (NCT01186796)
Timeframe: Withdrawal of blood samples (2.5 mL each) every 10 min for 6 hr. Sampling will begin at 0800 h and conclude at 1400 h.

Intervention	min (Mean)
	Mean Duration of GH Bursts post L-Arg/Saline	Mean Duration of GH Bursts post L-Arg/GHRH	Mean Duration of GH Bursts post L-Arg/Ghrelin	Mean Duration of GH Bursts post L-Arg/GHRH+Ghrelin
Fulvestrant Group	18.0	17.6	12.8	12.7
Saline Placebo Group	16.3	15.4	12.7	12.8

Mean GH Concentration (Pulsatile) in Response to Secretagogue

Subjects were administered 4 different secretagogues: (i) L-arginine/Saline, (ii) L-arginine/Ghrelin, (iii) L-arginine/GHRH, and (iv) L-arginine / GHRH + Ghrelin. The result was calculated by averaging values over the 6 hour collection timeframe. (NCT01186796)
Timeframe: Withdrawal of blood samples (2.5 mL each) every 10 min for 6 hr. Sampling will begin at 0800 h and conclude at 1400 h.

Intervention	ug/L/6h (Mean)
	Pulsatile GH Response to L-arg/saline	Pulsatile GH Response to L-Arg/GHRH	Pulsatile GH Response to L-arg/ghrelin	Pulsatile GH Response to L-arg/ghrelin + GHRH
Fulvestrant Group	22.6	46.6	66.9	214
Saline Placebo Group	17.3	17.4	66.8	178

Mean GH Half-Life in Response to Secretagogue

Intervention	min (Mean)
	Mean GH Half-life duration post L-Arg/Saline	Mean GH Half-life duration post L-Arg/GHRH	Mean GH Half-life duration post L-Arg/Ghrelin	Mean GH Half-life duration post L-Arg/GHRH+Ghrelin
Fulvestrant Group	15.4	17.2	19.4	19.0
Saline Placebo Group	15.0	17.5	19.0	19.1

Mean Mass of GH Released Per Burst in Response to Secretagogue

Intervention	ug/L (Mean)
	Mean Mass of GH per Burst post L-Arg/Saline	Mean Mass of GH per Burst post L-Arg/GHRH	Mean Mass of GH per Burst post L-Arg/Ghrelin	Mean Mass of GH per Burst post L-Arg/GHRH+Ghrelin
Fulvestrant Group	12.6	48.4	64.7	203
Saline Placebo Group	7.5	44.4	45.5	164

Objective Response Rate (ORR) Determined by Clinical Palpation

"Objective response rate is defined as the rate of participants with partial or complete responses according to RECIST V1.0.~Complete response is defined as the disappearance of all target lesions and partial response is defined as at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD (RECIST V1.0.)." (NCT00871858)
Timeframe: 6 months

Intervention	percentage of participants (Number)
Arm A (ANA)	58.9
Arm B (FULV)	53.8

Objective Response Rate (ORR) Determined by Mammography

Intervention	percentage of participants (Number)
Arm A (ANA)	26.1
Arm B (FULV)	27.8

Objective Response Rate (ORR) Determined by Ultrasound

Intervention	percentage of participants (Number)
Arm A (ANA)	35.1
Arm B (FULV)	52.4

Percentage of Participants With 5-year Relapse-Free Survival

"Relapse-Free survival (RFS) is measured from the date of randomization to the date of the following events, whichever occurs first according to the DATECAN recommendations for breast cancer:~Invasive ipsilateral breast tumor recurrence/ progression ;~Local invasive recurrence/progression ;~Regional invasive recurrence/progression (N+: regional progression) ;~Appearance/Occurrence of Metastatic recurrence;~Death whatever the cause.~Participants who did not experience events were censored at the date of last follow-up. RFS was estimated using the Kaplan-Meier method. No comparison test was performed between the two arms as this study is non-comparative." (NCT00871858)
Timeframe: 5 years

Intervention	Percentage of participants (Number)
Arm A (ANA)	82.8
Arm B (FULV)	74.7

Rate of Breast-conserving Surgery

breast-conserving surgery concerns patients who did not undergo mastectomy. (NCT00871858)
Timeframe: 6 months

Intervention	percentage of participants (Number)
Arm A (ANA)	60.7
Arm B (FULV)	50.0

Rate of Grade 3 or Higher Neutropenia

"The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.~Grade 3 neutropenia: <1000-500/mm^3; <1.0-0.5 x 10e9/L~Grade 4 neutropenia: <500/mm^3; <0.5 x 10e9/L" (NCT03007979)
Timeframe: Through the first 29 days of treatment

Intervention	Participants (Count of Participants)
Palbociclib + Letrozole or + Fulvestrant	10

Median Time of Progression-free Survival (PFS)

Progression free survival (PFS) was defined as the time in months from randomization to either the date the subject was first recorded as having PD (even if the subject went off treatment because of toxicity), or the date of death if the subject died due to any causes before progression. Progression=At least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. (NCT00754325)
Timeframe: Date of randomization to date of initial disease progression, or date of death (whichever occurs first), up to January 2014 (approximately 5 years)

Intervention	months (Median)
Fulvestrant and Dasatinib	5.6
Fulvestrant	5.3

Number of Participants With Best Overall Response

Best overall response rate (ORR) = number of participants with measurable lesions by Response Evaluation Criteria in Solid Tumors (RECIST) having a best response of complete response (CR) or partial response (PR) divided by number of randomized participants. RECIST 1.1 response criteria applies. To be recorded as best response, CR or PR had to be confirmed at ≥ 4 weeks interval. An unconfirmed CR was recorded as PR. (NCT00754325)
Timeframe: Date of randomization to date of initial disease progression, or date of death (whichever occurs first), up to January 2014 (approximately 5 years)

Intervention	participants (Number)
Fulvestrant and Dasatinib	1
Fulvestrant	2

Number of Participants With Disease Progression (PD) or Death

This endpoint evaluated the progression free survival (PFS) of participants amongst the total evaluable population. Progression free survival (PFS) was defined as the time from randomization to either the date the subject was first recorded as having PD (even if the subject went off treatment because of toxicity), or the date of death if the subject died due to any causes before progression. Participants with no recorded post-baseline tumor assessment had PFS censored at the day of randomization. Participants lost to follow-up were censored at the last date of contact. Participants that had not progressed or died had PFS censored at the date of last follow-up. (NCT00754325)
Timeframe: Date of randomization to date of initial disease progression, or date of death (whichever occurs first), up to January 2014 (approximately 5 years)

Intervention	participants (Number)
Fulvestrant and Dasatinib	35
Fulvestrant	40

Percentage of Participants With Clinical Benefit for At Least 6 Months

Clinical benefit rate (CBR) was defined as the percentage of participants that had Stable Disease (SD), complete response (CR), or partial response (PR) for greater than or equal to 6 months if there was no evidence of progression at or before assessment performed on or after Study Day 161. CR= Disappearance of all target lesions. No new lesions. PR= At least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. SD= Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) taking as reference the smallest sum LD since the treatment started. Physical examination, radiological assessment, and bone scans (if applicable) were used to assess outcome. (NCT00754325)
Timeframe: Date of randomization to date of initial disease progression, or date of death (whichever occurs first), up to January 2014 (approximately 5 years)

Intervention	percentage of participants (Number)
Fulvestrant and Dasatinib	38.0
Fulvestrant	42.9

Percentage of Participants With Progression Free Survival (PFS) at 6 Months

PFS rate was defined as the percentage of participants experiencing no disease progression or death from any cause at 6 months after randomization. Progression free survival (PFS) was defined as the time from randomization to either the date the subject was first recorded as having PD (even if the subject went off treatment because of toxicity), or the date of death if the subject died due to any causes before progression. Progression=At least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Kaplan Meier assessments were used to estimate the percentages. (NCT00754325)
Timeframe: at 6 months

Intervention	percentage of participants (Number)
Fulvestrant and Dasatinib	48.1
Fulvestrant	44.6

Number of Participants With Complete Response (CR) , Partial Response (PR), Stable Disease (SD), and Disease Progression (PD)

Table represents the best response achieved over this time frame. CR = Disappearance of all target lesions. No new lesions. PR = At least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. SD = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) taking as reference the smallest sum LD since the treatment started. Progression (PD): At least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. (NCT00754325)
Timeframe: Date of randomization to date of initial disease progression, or date of death (whichever occurs first), up to January 2014 (approximately 5 years)

Intervention	participants (Number)
	Complete Response, CR	Partial Response, PR	Stable Disease, SD	Disease Progression, PD	Not Evaluable
Fulvestrant	0	3	28	16	2
Fulvestrant and Dasatinib	0	1	34	11	4

Number of Participants With Serious Adverse Events, Death, and Discontinuation Due to Adverse Events

Adverse event (AE) defined: any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Serious adverse event (SAE) defined: a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. (NCT00754325)
Timeframe: Date of randomization to date of initial disease progression, or date of death (whichever occurs first), up to January 2014 (approximately 5 years)

Intervention	participants (Number)
	Serious Adverse Events	Deaths	Discontinued due to AEs
Fulvestrant	11	16	6
Fulvestrant and Dasatinib	14	15	7

Number of Participants With Negative Human Anti-Human Antibodies (HAHAs)

Negative human anti-human antibodies were defined as <6.64 (NCT00372996)
Timeframe: Predose on Day 1 of Cycle 1 and at 150 days post last CP-751,871 infusion

Intervention	participants (Number)
CP-751,871 + Exemestane	37

Percentage of Participants Achieving Complete Response (CR), Partial Response (PR), or Stable Disease (SD) Maintained for at Least 6 Months

Objective responses were defined using RECIST as CR: disappearance of all target and nontarget lesions. PR: at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as a reference the baseline sum LD. Nontarget lesions may persist provided there is no unequivocal progression in these lesions. SD: measurements demonstrating neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify as progressive disease (PD) during the first 6 weeks after the start of treatment taking as reference the smallest sum LD since the treatment started. During this time, nontarget lesions may persist provided there is no unequivocal progression in these lesions. (NCT00372996)
Timeframe: Baseline, Day 1 of Cycles 2 and 4 and then Day 1 of every 3rd cycle starting at Cycle 7 up to 60 months

Intervention	percentage of participants (Number)
CP-751,871 + Exemestane	68.9
Exemestane	64.1

PFS in Participants With Hemoglobin A1c (HbA1c) Less Than (<) 5.7% at Baseline

PFS was calculated from the time of randomization to either progression of disease, death, or treatment discontinuation because of unsatisfactory therapy results (such as global deterioration of health status). Disease progression was defined as 1 or more of the following: radiographic progression (20% increase in measurable lesions, appearance of new lesions or unequivocal progression of evaluable lesions as defined by RECIST); occurrence of new pleural/pericardial effusions or ascites confirmed by positive cytology; persistent hypercalcemia requiring more than 2 IV treatments with bisphosphonates; intervention for any cancer-related events (radiations, surgery) or new symptoms related to tumor growth requiring participant discontinuation; development of brain metastasis; or death for any cause. Median PFS was estimated from the Kaplan-Meier curve. 95% CI is based on the Brookmeyer and Crowley method. (NCT00372996)
Timeframe: Baseline, Day 1 of Cycles 2 and 4 and then Day 1 of every 3rd cycle starting at Cycle 7 up to 60 months

Intervention	months (Median)
CP-751,871 + Exemestane	13.2
Exemestane	9.9

Progression-Free Survival (PFS)

PFS was calculated from the time of randomization to either progression of disease, death, or treatment discontinuation because of unsatisfactory therapy results (such as global deterioration of health status). Disease progression was defined as 1 or more of the following: radiographic progression (20 percent [%] increase in measurable lesions, appearance of new lesions or unequivocal progression of evaluable lesions as defined by Response Evaluation Criteria in Solid Tumors [RECIST]); occurrence of new pleural/pericardial effusions or ascites confirmed by positive cytology; persistent hypercalcemia requiring more than 2 IV treatments with bisphosphonates; intervention for any cancer-related events (radiations, surgery) or new symptoms related to tumor growth requiring participant discontinuation; development of brain metastasis; or death for any cause. Median PFS was estimated from the Kaplan-Meier curve. 95% confidence interval (CI) is based on the Brookmeyer and Crowley method. (NCT00372996)
Timeframe: Baseline, Day 1 of Cycles 2 and 4 and then Day 1 of every 3rd cycle starting at Cycle 7 up to 60 months

Intervention	months (Median)
CP-751,871 + Exemestane	11.0
Exemestane	9.2

Patients Event-free at 12 Months (Where Event = Death (From Any Cause), Disseminated Tumour Cells (DTC) Positive at 12 Months or Clinical Disease Recurrence)

Number of patients event-free (NCT00357110)
Timeframe: 12 month period following randomisation

Intervention	Participants (Number)
Fulvestrant + Anastrozole	6
Anastrozole	7

Clinical Benefit Rate (CBR)

CBR was defined as the proportion of all randomised patients who had clinical benefit (response of CR, PR or SD>=24 weeks. (NCT00313170)
Timeframe: The planned data cut-off for this study was when all patients, except withdrawals, had been followed up for at least 24 weeks. Patients received treatment up to approximately 2 years.

Intervention	Percentage of patients (Number)
Fulvestrant 250 mg	31.9
Fulvestrant 250 mg + Loading Dose	47.1
Fulvestrant 500 mg	47.8

Duration of Response (DoR)

DoR was defined as the time from date of first documentation of the response (CR or PR) until the date of disease progression or death from any cause. (NCT00313170)
Timeframe: The planned data cut-off for this study was when all patients, except withdrawals, had been followed up for at least 24 weeks. Patients received treatment up to approximately 2 years.

Intervention	Days (Median)
Fulvestrant 250 mg	NA
Fulvestrant 250 mg + Loading Dose	NA
Fulvestrant 500 mg	539

Objective Response (ORR)

Objective response rate was defined as percentage of patients with either complete response (CR - disappearance of all target lesions) or partial response (PR - at least 30% decrease in the sum of diameters of target lesions). All patients were to be followed up every 12 weeks for progression, defined by response evaluation criteria in solid tumors (RECIST v1.1). (NCT00313170)
Timeframe: The planned data cut-off for this study was when all patients, except withdrawals, had been followed up for at least 24 weeks. Patients received treatment up to approximately 2 years.

Intervention	Percentage of patients (Number)
Fulvestrant 250 mg	8.5
Fulvestrant 250 mg + Loading Dose	5.9
Fulvestrant 500 mg	15.2

Pharmacokinetic Parameter: Mean Population Clearance, a Measure of the Efficiency With Which Fulvestrant is Eliminated From the Body

Intervention	litres per hour (Least Squares Mean)
Fulvestrant	31

Time to Progression (TTP)

Time from randomisation until objective disease progression or death (in the absence of objective progression) using the Kaplan-Meier method. RECIST tumor assessments were carried out every 12 weeks until progression. (NCT00313170)
Timeframe: The planned data cut-off for this study was when all patients, except withdrawals, had been followed up for at least 24 weeks. Patients received treatment up to approximately 2 years.

Intervention	Days (Median)
Fulvestrant 250 mg	88
Fulvestrant 250 mg + Loading Dose	172
Fulvestrant 500 mg	169

Pharmacokinetic Parameter: Mean Volume of Distribution at Steady State, a Measure of the Apparent Volume in the Body Into Which Fulvestrant Distributes

A 2-compartment model with a 1st order absorption and 1st order elimination process was fitted to the fulvestrant concentration-time data. Relative standard error is reported for the mean. The mean estimate of volume of distribution at steady state was reported as the sum of V1/F and V2/F in the clinical study report. (NCT00313170)
Timeframe: Baseline to 12 weeks

Intervention	Liters (Least Squares Mean)
	V1/F	V2/F
Fulvestrant	20600	35700

Clinical Benefit Rate (CBR)

A Clinical Benefit (CB) responder is defined as a patient having a best overall response of Complete response (CR), Partial Response (PR) or Stable disease (SD) provided SD (or better) was present = 154 days from randomization (ie SD = 24 weeks with the 2 week RECIST assessment time window allowed). The Clinical Benefit Rate is the percentage of patients with CB. (NCT00305448)
Timeframe: every 12 weeks(+/- 2 weeks) from randomization to data up to data cut-off, 19th March 2008.

Intervention	percentage of participants (Number)
Fulvestrant 250 mg	42.2
Fulvestrant 250 mg + Loading Dose	54.9
Fulvestrant 500 mg	46.8

Objective Response Rate (ORR)

"An objective response (OR) is defined as a patient having a best overall response of either complete response (CR) or partial response (PR). A patient has best overall response of CR if she had overall response of CR or PR on one visit and met the confirmation criteria per RECIST. ORR is defined as percentage of patients with objective response.~Each patient with measurable disease at baseline was assessed for OR from the sequence of Response Evaluation Criteria in Solid Tumors (RECIST) scan data up to data cut-off. RECIST scans were performed every 12 weeks (+/- 2weeks) from randomization" (NCT00305448)
Timeframe: baseline and every 12 weeks (+/- 2weeks) from randomization data up to data cut-off (19th march 2008)

Intervention	percentage of participants (Number)
Fulvestrant 250 mg	11.1
Fulvestrant 250 mg + Loading Dose	17.6
Fulvestrant 500 mg	10.6

Pharmacokinetic Parameter: Mean Population Clearance, a Measure of the Efficiency With Which Fulvestrant is Eliminated From the Body

The measure of dispersion for mean population clearance is based on the estimated inter-individual variance (NCT00305448)
Timeframe: Baseline to 12 weeks

Intervention	L/h (Mean)
Fulvestrant	34.4

Pharmacokinetic Parameter: Mean Volume of Distribution at Steady State, a Measure of the Apparent Volume in the Body Into Which Fulvestrant Distributes

The measure of dispersion for volume of distribution is based on the inter-individual variance estimated for the apparent volume of plasma into which Fulvestrant distributes (NCT00305448)
Timeframe: Baseline to 12 weeks

Intervention	Vss/F (L) (Mean)
Fulvestrant	35300

Time to Progression (TTP)

Time (in days) from randomization until objective disease progression or death (in the absence of objective progression). RECIST tumour assessments carried out every 12 weeks from randomization (+/- 2 weeks) until data cut-off on 19th March 2008. (NCT00305448)
Timeframe: every 12 weeks from randomization (+/- 2 weeks) until data cut-off (19th march 2008)

Intervention	days (Median)
Fulvestrant 250 mg	169
Fulvestrant 250 mg + Loading Dose	211
Fulvestrant 500 mg	169

Clinical Benefit Rate

"Clinical Benefit is defined as the number of patients having a best overall tumour response of CR/PR or SD for ≥6 months.~The Clinical Benefit rate is defined as the number of responders divided by the number in the Intention-to-treat (ITT) analysis set: responder=overall best response of complete response (CR)/partial response (PR) or stable disease (SD) for at least 6 months (calculated from the date of randomisation) as defined by RECIST criteria at any point prior to the data cut-off." (NCT00454805)
Timeframe: Every 8 weeks until progression or discontinuation

Intervention	Ratio (Number)
Cediranib 45 mg	0.419
Placebo	0.419

Duration of Clinical Benefit

Number of days from date of clinical benefit to date of progression. Clinical benefit is defined as having a best overall tumour response of CR/PR or SD for ≥6 months. (NCT00454805)
Timeframe: Every 8 weeks until progression or discontinuation

Intervention	Days (Mean)
Cediranib 45 mg	306.6
Placebo	343.8

Duration of Response

Number of days from date of response (complete/partial based on RECIST) to date of progression (NCT00454805)
Timeframe: Every 8 weeks until progression or discontinuation

Intervention	Days (Median)
Cediranib 45 mg	207.5
Placebo	224.0

Objective Response Rate

"Best objective tumour response (based on Response Evaluation Criteria in Solid Tumours (RECIST)) during the study for patients with measurable disease. Best objective tumour response defined as:~Complete Response (CR) Disappearance of all target lesions Partial response (PR) At least a 30% decrease in the sum of longest diameters (LDs) of target lesions, taking as reference the baseline sum of LDs.~Progression (PD) At least a 20% increase in the sum of LDs of target lesions, taking as reference the smallest sum of LDs since treatment started (including the baseline sum of LDs) and at least 5 mm increase.~Stable disease (SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD" (NCT00454805)
Timeframe: RECIST performed at screening and every 8 weeks through to progression or discontinuation whichever is earliest.

Intervention	Participants (Number)
Cediranib 45 mg	4
Placebo	1

Progression Free Survival

Number of months from randomisation until progressive disease based on RECIST (progression of target lesions, clear progression of existing non-target lesions or the appearance of one or more new lesions) or death in the absence of progression. (NCT00454805)
Timeframe: RECIST performed at screening and every 8 weeks through to progression or discontinuation whichever is earliest.

Intervention	Days (Median)
Cediranib 45 mg	223
Placebo	112

Duration of Response

For patients with complete or partial response, duration of response is defined as days from first recorded response to the first date of recurrent or progression or death. (NCT02630693)
Timeframe: 2 years

Intervention	days (Median)
Palbociclib (100mg)	126
Palbociclib (125mg)	169

Overall Survival

Time from randomization to death of any cause. (NCT02630693)
Timeframe: 2 years

Intervention	months (Median)
Palbociclib (100mg)	20.73
Palbociclib (125mg)	21.39

Progression Free Survival Using the RECIST 1.1 Criteria

progression free survival (PFS) is defined as time from randomization to progression or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT02630693)
Timeframe: 2 years

Intervention	months (Median)
Palbociclib (100mg)	9.33
Palbociclib (125mg)	11.30

Duration Of Responses

The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started, or death due to any cause. Participants without events reported are censored at the last disease evaluation). (NCT03289039)
Timeframe: 2 years

Intervention	months (Number)
Neratinib	NA
Neratinib + Fulvestrant	6.7

Overall Response Rate

Intervention	Participants (Count of Participants)
Neratinib	0
Neratinib + Fulvestrant	1

Overall Survival

Overall Survival (OS) is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive. Participants will be evaluated every 6 months for survival until death. Participants removed from protocol therapy for unacceptable adverse event(s) will be followed until resolution or stabilization of the adverse event. (NCT03289039)
Timeframe: Participants were followed for up to 38.4 months (3 years and 2 months) from registration to removal from protocol therapy or death.

Intervention	months (Median)
	Less than 4 prior lines of therapy; no prior fulvestrant use	More than 3 prior lines of therapy; no prior fulvestrant use
Neratinib + Fulvestrant	12.22	19.91

Overall Survival

Intervention	months (Median)
	Less than 4 prior lines of therapy; no prior fulvestrant use	More than 3 prior lines of therapy; no prior fulvestrant use	More than 3 prior lines of therapy; prior fulvestrant use
Neratinib	NA	20.17	27.79

Progression Free Survival

"Progression-Free Survival (PFS) is defined as the time from randomization (or registration) to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation.~Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Disease assessment were conducted at baseline and every two cycles after the first cycle." (NCT03289039)
Timeframe: Participants were followed for PFS up to 20.3 months from registration.

Intervention	months (Median)
	Less than 4 prior lines of therapy; no prior use of fulvestrant	More than 3 prior lines of therapy; no prior use of fulvestrant
Neratinib + Fulvestrant	1.74	3.84

Progression Free Survival

Intervention	months (Median)
	Less than 4 prior lines of therapy; no prior use of fulvestrant	More than 3 prior lines of therapy; no prior use of fulvestrant	More than 3 prior lines of therapy; prior use of fulvestrant
Neratinib	19.58	1.81	6.42

Percentage of Participants Who Exhibit Stable Disease (SD) or CR or PR [Disease Control Rate (DCR)]

Disease control rate (DCR) is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. (NCT02763566)
Timeframe: Randomization to Measured Progressive Disease (up to 26 Months)

Intervention	percentage of participants (Number)
Abemaciclib + Nonsteroidal Aromatase Inhibitor (NSAI)	91.3
Placebo + NSAI	82.8
Abemaciclib + Fulvestrant	92.3
Placebo + Fulvestrant	69.8

Percentage of Participants With Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]

Objective response rate is the percentage of participants with a BOR of CR or PR as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. (NCT02763566)
Timeframe: Randomization to Measured Progressive Disease (up to 26 Months)

Intervention	percentage of participants (Number)
Abemaciclib + Nonsteroidal Aromatase Inhibitor (NSAI)	56.0
Placebo + NSAI	30.3
Abemaciclib + Fulvestrant	38.5
Placebo + Fulvestrant	7.5

Percentage of Participants With Best Overall Response of CR, PR, or SD With Duration of SD for at Least 6 Months [Clinical Benefit Rate (CBR)]

Clinical benefit rate (CBR) is the percentage of participants with a BOR of CR or PR, or SD for at least 6 months. CR is defined as the disappearance of all target and non-target lesions & no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. (NCT02763566)
Timeframe: Randomization to Measured Progressive Disease (up to 26 Months)

Intervention	percentage of participants (Number)
Abemaciclib + Nonsteroidal Aromatase Inhibitor (NSAI)	82.6
Placebo + NSAI	62.6
Abemaciclib + Fulvestrant	77.9
Placebo + Fulvestrant	45.3

Progression Free Survival (PFS) (Abemaciclib + Fulvestrant and Placebo + Fulvestrant Arms)

Progression-free survival time was measured from randomization until the date of objective progression as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1), or death from any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Patients who have neither progressed nor died were censored at the day of their last radiographic tumor assessment, if available, or date of randomization if no post-baseline radiographic assessment is available. (NCT02763566)
Timeframe: Randomization to Measured Progressive Disease or Death (up to 26 Months)

Intervention	Months (Median)
Abemaciclib + Fulvestrant	11.47
Placebo + Fulvestrant	5.59

Progression Free Survival (PFS) (Abemaciclib + NSAI & Placebo NSAI)

Intervention	Months (Median)
Abemaciclib + Nonsteroidal Aromatase Inhibitor (NSAI)	NA
Placebo + NSAI	14.73

Change From Randomization in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)

"consists of 30 items covered by 1 of 3 dimensions:~Global health status/quality of life (2 items) with scores ranging from 1 (Very Poor) to 7 (Excellent).~Functional scales (15 total items addressing either physical, role, emotional, cognitive, or social functioning), each item scores ranging from 1 (not at all) to 4 (very much)~Symptom scales (13 total items addressing either fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, or financial impact), each item scores ranging from 1 (not at all) to 4 (very much).~Raw scores are linearly converted to a 0-100 scale with higher scores reflecting higher levels of function/QOL or higher levels of symptom burden." (NCT02763566)
Timeframe: Baseline through 19 Months

,,,

Intervention	score on a scale (Least Squares Mean)
	Global Health Status	Functional Scales - Physical Functioning	Functional Scales - Role Functioning	Functional Scales - Emotional Functioning	Functional Scales - Cognitive Functioning	Functional Scales - Social Functioning	Symptom Scales - Fatigue	Symptom Scales - Nausea and Vomiting	Symptom Scales - Pain	Symptom Scales - Dyspnoea	Symptom Scales - Insomnia	Symptom Scales - Appetite	Symptom Scales - Constipation	Symptom Scales - Diarrhoea	Symptom Scales - Financial Difficulties
Abemaciclib + Fulvestrant	-0.35	-1.11	-3.76	0.43	-3.52	-2.03	4.19	4.26	-2.82	-1.66	1.53	8.67	-1.63	16.03	-6.36
Abemaciclib + Nonsteroidal Aromatase Inhibitor (NSAI)	2.38	-0.78	-1.69	1.57	-2.89	-2.45	1.63	0.62	-5.44	2.51	-0.87	4.19	-3.05	15.72	-3.02
Placebo + Fulvestrant	3.12	-2.70	-2.04	0.18	-1.10	-2.67	1.46	1.67	-0.17	0.83	-0.44	1.21	0.65	-1.80	-9.35
Placebo + NSAI	4.26	-0.01	-1.38	-0.10	-0.72	-1.57	0.06	-0.33	-4.90	0.35	-0.05	-1.47	-1.49	-0.10	-1.27

Pharmacokinetics (PK): Area Under the Concentration Curve of Abemaciclib, Its Metabolites (M2 & M20)

"Pharmacokinetics (PK): Area Under the Concentration Curve of Abemaciclib and its Metabolites LSN2839567 (M2) & LSN3106726 (M20) was reported.~C=Cycle, D=day;" (NCT02763566)
Timeframe: C1D1 post dose, C2D1 post dose, C3D1 predose, C4D1 predose

Intervention	Nanogramhour per Millilitre (ngh/mL) (Geometric Mean)
	Abemaciclib	LSN2839567 (M2)	LSN3106726 (M20)
Abemaciclib + Fulvestrant	2740	861	1570
Abemaciclib + Nonsteroidal Aromatase Inhibitor (NSAI)	2720	1080	1970

Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf)

The mBPI-sf is an 11-item instrument used as a multiple-item measure of cancer pain intensity. In addition to pain intensity (4 items), the mBPI-sf is designed for participants to record the presence of pain in general, pain relief, and pain interference with function (general activity, mood, ability to walk, ability to perform normal work, relations with others, sleep, enjoyment of life). Responses for the mBPI-sf items are captured through the use of 11-point numeric rating scales anchored at 0 (no pain or does not interfere) and 10 (pain as bad as you can imagine or completely interferes). The mBPI-sf recall period is 24 hours and typical completion time for this instrument is less than 5 minutes. Mean Interference Score data is reported here. Least square (LS) Mean value was controlled for Treatment, visit, Treatment*Visit and baseline. (NCT02675231)
Timeframe: Baseline, 30 Days After Treatment Discontinuation (Up To 36 Months)

Intervention	units on a scale (Least Squares Mean)
150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant	0
150 mg Abemaciclib + 8 mg/kg Trastuzumab	0.20
8 mg/kg Trastuzumab + Standard of Care Chemotherapy	0.31

Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score

The EQ-5D-5L is a standardized instrument for use as a measure of self-reported health status. Participants completed the 5-level (no problem, slight problem, moderate problem, severe problem, and inability or extreme problem), 5-dimension (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) questionnaire concerning their current health state. Five dimensions of health status are each assessed with 5 response options and scored as a composite index which were anchored on a scale of 0 to 1 with a higher score representing better health status.LS Mean value was controlled for Treatment, visit, Treatment*Visit and baseline. (NCT02675231)
Timeframe: Baseline, 30 Days After Treatment Discontinuation (Up To 36 Months)

Intervention	units on a scale (Least Squares Mean)
150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant	0.01
150 mg Abemaciclib + 8 mg/kg Trastuzumab	-0.01
8 mg/kg Trastuzumab + Standard of Care Chemotherapy	-0.04

Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS)

European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a standardized measure of health status of the participant. The EQ-5D-5L is assessed using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine. A higher score indicates better health state. LS Mean value was controlled for Treatment, visit, Treatment*Visit and baseline. (NCT02675231)
Timeframe: Baseline, 30 Days After Treatment Discontinuation (Up To 36 Months)

Intervention	millimeter (mm) (Least Squares Mean)
150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant	0.61
150 mg Abemaciclib + 8 mg/kg Trastuzumab	-1.64
8 mg/kg Trastuzumab + Standard of Care Chemotherapy	-0.61

Duration of Response (DoR)

DoR was the time from the date of first evidence of complete response or partial response to the date of objective progression or the date of death due to any cause, whichever is earlier. CR and PR were defined using the RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. If a responder was not known to have died or have objective progression as of the data inclusion cutoff date, duration of response was censored at the last adequate tumor assessment date. (NCT02675231)
Timeframe: Date of CR or PR to Date of Objective Disease Progression or Death from Any Cause (Up To 36 Months)

Intervention	Months (Median)
150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant	12.5
150 mg Abemaciclib + 8 mg/kg Trastuzumab	9.5
8 mg/kg Trastuzumab + Standard of Care Chemotherapy	NA

Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)

Intervention	Percentage of participants (Number)
150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant	32.9
150 mg Abemaciclib + 8 mg/kg Trastuzumab	13.9
8 mg/kg Trastuzumab + Standard of Care Chemotherapy	13.9

Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR)

Disease Control Rate (DCR) was the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. (NCT02675231)
Timeframe: Baseline to Objective Disease Progression (Up To 36 Months)

Intervention	Percentage of participants (Number)
150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant	78.5
150 mg Abemaciclib + 8 mg/kg Trastuzumab	74.7
8 mg/kg Trastuzumab + Standard of Care Chemotherapy	67.1

Percentage of Participants With Best Overall Response of CR, PR, or SD With Duration of SD for at Least 6 Months: Clinical Benefit Rate (CBR)

Clinical benefit rate defined as percentage of participants with best overall response of CR, PR, or SD with a duration of at least 6 months. CR, PR, or SD were defined using RECIST, v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. Percentage of participants = (participants with CR+PR+SD with a duration of at least 6 months /number of participants enrolled) *100. (NCT02675231)
Timeframe: Date of CR, PR or SD to 6 Months Post CR, PR or SD (Up To 36 Months)

Intervention	Percentage of participants (Number)
150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant	58.2
150 mg Abemaciclib + 8 mg/kg Trastuzumab	45.6
8 mg/kg Trastuzumab + Standard of Care Chemotherapy	38.0

Progression Free Survival (PFS)

PFS time was measured from the date of randomization to the date of investigator-determined objective progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of first dose, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date. (NCT02675231)
Timeframe: Baseline to Progressive Disease or Death from Any Cause (Up To 36 Months)

Intervention	Months (Median)
150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant	8.3
150 mg Abemaciclib + 8 mg/kg Trastuzumab	5.7
8 mg/kg Trastuzumab + Standard of Care Chemotherapy	5.7

Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)

EORTC QLQ-C30 v3.0 was a self-administered questionnaire with multidimensional scales that measures 5 functional domains (physical, role, cognitive, emotional, and social), global health status, and symptom scales of fatigue, pain, nausea and vomiting, dyspnea, loss of appetite, insomnia, constipation and diarrhea, and financial difficulties. A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For functional domains and global health status, higher scores represent a better level of functioning. For symptoms scales, higher scores represented a greater degree of symptoms. LS Mean value was controlled for Treatment, visit, Treatment*Visit and baseline. (NCT02675231)
Timeframe: Baseline, 30 Days After Treatment Discontinuation (Up To 36 Months)

Intervention	units on a scale (Least Squares Mean)
	Global health status	Functional scale: Physical functioning	Functional scale: Role functioning	Functional scale: Emotional functioning	Functional scale: Cognitive functioning	Functional scale: Social functioning	Symptom scale: Fatigue	Symptom scale: Nausea and vomiting	Symptom scale: Pain	Symptom scale: Dyspnoea	Symptom scale: Insomnia	Symptom scale: Appetite loss	Symptom scale: Constipation	Symptom scale: Diarrhoea	Symptom scale: Financial difficulties
150 mg Abemaciclib + 8 mg/kg Trastuzumab	-5.9	-4.4	-5.0	-0.4	-1.1	-0.9	7.0	5.6	3.1	2.9	-1.6	5.5	-10.5	25.3	-1.9
150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant	-2.9	-1.0	-2.7	2.4	-1.8	-0.9	1.8	6.3	-2.5	0.7	-4.4	6.3	-6.3	21.5	0.8
8 mg/kg Trastuzumab + Standard of Care Chemotherapy	-1.9	-4.5	-8.2	1.1	-1.6	-2.4	4.7	2.2	4.3	3.7	2.0	2.4	-3.4	2.2	-3.2

Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib and Its Metabolites (M2 and M20)

Minimum Steady State Concentration (Cmin,ss) of Abemaciclib and Its Metabolites (M2 and M20) was evaluated. M2 and M20 are 2 major active metabolites of abemaciclib. (NCT02675231)
Timeframe: Cycle(C)1 Day(D)1,C1D15, C2D1, C2D8, C3D1,C3D15, C4D1, C5D1:pre-dose; C1D1, C2D1, C3D1, C4D1, C5D1:post-dose

Intervention	nanogram/milliliter (ng/mL) (Geometric Mean)
	Abemaciclib	M2	M20
150 mg Abemaciclib + 8 mg/kg Trastuzumab	155	96.5	181
150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant	134	72.0	136

Change in Bone Age Advancement Over the First 6 Month Trial Period.

Change in the rate of increase in bone age from pre treatment (based on the 6 month retrospective visit) to the first 6 months of the treatment period. Bone age advancement for a particular time period was calculated as the increase in bone age over that time period adjusted (ie, normalized) for the length of that time period. (NCT00278915)
Timeframe: baseline to first 6 months of the treatment period

Intervention	cm/year (Mean)
Fulvestrant	-0.83

Change in Bone Age Advancement Over the Second 6 Month Trial Period.

Change in the rate of increase in bone age from pre treatment (based on the 6 month retrospective visit) to the second 6 months of the treatment period. Bone age advancement for a particular time period was calculated as the increase in bone age over that time period adjusted (ie, normalized) for the length of that time period. (NCT00278915)
Timeframe: baseline to second 6 months of the treatment period.

Intervention	cm/year (Mean)
Fulvestrant	-1.10

Change in Bone Age Advancement Over the Whole 12 Month Trial Period.

Change in the rate of increase in bone age from pre treatment (based on the 6 month retrospective visit) to the full 12 month treatment period. (Using last value carried forward method for the one patient who withdrew soon after their month 6 bone scan) Bone age advancement for a particular time period was calculated as the increase in bone age over that time period adjusted (ie, normalized) for the length of that time period. (NCT00278915)
Timeframe: 6 month pre-treatment observation period (baseline) followed by 12 month treatment period (on treatment period)

Intervention	cm/year (Mean)
Fulvestrant	-0.93

Change in Breast Tanner Stage From Baseline to Month 12.

Change in breast Tanner stage from baseline to Month 12/last visit. Tanner stage (breast) is a score of range 1-5 where 1=no development and 5=adult breast (NCT00278915)
Timeframe: 6 month pre-treatment observation period (result at Month 0 considered as baseline) followed by 12 month treatment period (on treatment period).

Intervention	units on a scale (Median)
Fulvestrant	0.0

Change in Growth Velocity (Annualised Growth Velocity i.e. cm/y) Over the First 6 Month Trial Period.

Change in growth velocity (annualised growth velocity.i.e. cm/y) from the pre treatment period to the first 6 months of the treatment period. Growth velocity for a particular time period was calculated as the increase in height over that time period divided by the length of that time period (expressed in cm/year) (NCT00278915)
Timeframe: 6 month pre-treatment observation period (baseline) followed by 6 month treatment period (on treatment period)

Intervention	cm/year (Mean)
Fulvestrant	-1.7

Change in Growth Velocity (Annualised Growth Velocity i.e. cm/y) Over the Second 6 Month Trial Period.

Change in growth velocity (annualised growth velocity i.e. cm/y) from the pre treatment period to the second 6 months of the treatment period. Growth velocity for a particular time period was calculated as the increase in height over that time period divided by the length of that time period (expressed in cm/year) (NCT00278915)
Timeframe: 6 month pre-treatment observation period (baseline) followed by 12 month treatment period (on treatment period)

Intervention	cm/year (Mean)
Fulvestrant	-0.8

Change in Growth Velocity (Annualised Growth Velocity i.e. cm/y) Over the Whole 12 Month Trial Period.

Change in growth velocity (annualised growth velocity i.e. cm/y) from the pre treatment period to the full 12 month treatment period. Growth velocity for a particular time period was calculated as the increase in height over that time period divided by the length of that time period (expressed in cm/year) (NCT00278915)
Timeframe: 6 month pre-treatment observation period (baseline) followed by 12 month treatment period (on treatment period)

Intervention	cm/year (Mean)
Fulvestrant	-1.4

Change in Growth Velocity (Z-Score) Over the First 6 Month Trial Period.

Change from pre-treatment period to the first 6 months of the treatment period. Z-score is [(growth velocity from the previous visit to the current visit - mean) / standard deviation(SD)], where the mean and SD are from the National Center for Health Statistics, Fels study. (NCT00278915)
Timeframe: 6 month pre-treatment observation period (baseline) followed by 6 month treatment period (on treatment period)

Intervention	Z-Score (Mean)
Fulvestrant	-1.60

Change in Growth Velocity (Z-Score) Over the Second 6 Month Trial Period.

Change in growth velocity (Z-Score) from pre-treatment to the second 6 months of the treatment period. Z-score is [(growth velocity from the previous visit to the current visit - mean) / standard deviation(SD)], where the mean and SD are from the National Center for Health Statistics, Fels study. (NCT00278915)
Timeframe: 6 month pre-treatment observation period (baseline) followed by 12 month treatment period (on treatment period)

Intervention	Z-score (Mean)
Fulvestrant	-0.64

Change in Growth Velocity (Z-Score) Over the Whole 12 Month Trial Period.

Change in growth velocity (Z-Score) from pre-treatment to the full 12 month treatment period. Z-score is [(growth velocity from the previous visit to the current visit - mean) / standard deviation(SD)], where the mean and SD are from the National Center for Health Statistics, Fels study. (NCT00278915)
Timeframe: 6 month pre-treatment observation period (baseline) followed by 12 month treatment period (on treatment period)

Intervention	Z-Score (Mean)
Fulvestrant	-1.14

Change in Ovarian Volume From Baseline to Month 12 by Ultrasound.

(NCT00278915)
Timeframe: Screening visit (baseline), Months 6 and 12 during the treatment period.

Intervention	cm^3 (Median)
Fulvestrant	1.01

Change in Ovarian Volume From Baseline to Month 6 by Ultrasound.

(NCT00278915)
Timeframe: Screening visit (baseline), Months 6 and 12 during the treatment period.

Intervention	cm^3 (Median)
Fulvestrant	0.10

Change in Ovarian Volume From Month 6 to Month 12 by Ultrasound.

(NCT00278915)
Timeframe: Screening visit (baseline), Months 6 and 12 during the treatment period.

Intervention	cm^3 (Median)
Fulvestrant	0.76

Change in Predicted Adult Height (PAH) From Baseline to Month 12.

Change in PAH from baseline to Month 12/final visit for patients equal to or over 6 years of age. (NCT00278915)
Timeframe: 6 month pre-treatment observation period (result at Screening considered as baseline) followed by 12 month treatment period (on treatment period).

Intervention	cm (Mean)
Fulvestrant	0.5

Change in Pubic Tanner Stage From Baseline to Month 12.

Change in pubic Tanner stage from baseline to Month 12/last visit. Tanner stage (pubic) is a score of range 1-5 where 1=no development and 5=adult pubic hair (NCT00278915)
Timeframe: 6 month pre-treatment observation period (result at Month 0 considered as baseline) followed by 12 month treatment period (on treatment period).

Intervention	units on a scale (Median)
Fulvestrant	0.0

Change in the Frequency of Annualised Days of Vaginal Bleeding

Change in the frequency of annualised days of vaginal bleeding during the 12 month treatment period compared to the 6 month baseline period, based on a worst-case scenario calculation .i.e. missing diary card days counted as bleeding days. (NCT00278915)
Timeframe: 6 month pre-treatment observation period (baseline) followed by 12 month treatment period (on treatment period)

Intervention	days per year (Median)
Fulvestrant	-3.6

Change in Uterine Volume From Baseline to Month 12 by Ultrasound.

Uterine volume was calculated via ultrasound using the formula: 0.5(longitudinal multiplied by anteroposterior multiplied by transverse), if all 3 linear dimensions were recorded. If all 3 linear dimensions were not recorded, uterine volume was not calculated. (NCT00278915)
Timeframe: Screening visit (baseline) and Month 12 during the treatment period.

Intervention	cm^3 (Median)
Fulvestrant	-2.44

Change in Uterine Volume From Baseline to Month 6 by Ultrasound.

Intervention	cm^3 (Median)
Fulvestrant	-1.10

Change in Uterine Volume From Month 6 to Month 12 by Ultrasound.

Intervention	cm^3 (Median)
Fulvestrant	-0.13

Hormone Assays: Follicle-stimulating Hormone (FSH).

Hormone assays: follicle-stimulating hormone (FSH)at Screening visit (baseline), Month 12 of the treatment period. Results presented relate to Month 12 of the treatment period.. (NCT00278915)
Timeframe: Month 12 of the treatment period.

Intervention	IU/Litres (Mean)
Fulvestrant	1.13

Hormone Assays: Luteinizing Hormone (LH).

Hormone assays: Luteinizing hormone (LH) at Screening visit (baseline), Month 12 of the treatment period. Results presented relate to Month 12 of the treatment period. (NCT00278915)
Timeframe: Month 12 of the treatment period.

Intervention	IU/Litres (Mean)
Fulvestrant	0.11

Hormone Assays: Serum Oestradiol.

Hormone assays: serum oestradiol at Screening visit (baseline), Month 12 of the treatment period. Results presented relate to Month 12 of the treatment period. (NCT00278915)
Timeframe: Month 12 of the treatment period.

Intervention	pmol/Litres (Mean)
Fulvestrant	25.95

Hormone Assays: Testosterone.

Hormone assays: testosterone at Screening visit (baseline), Month 12 of the treatment period. Results presented relate to Month 12 of the treatment period.. (NCT00278915)
Timeframe: Month 12 of the treatment period.

Intervention	nmol/Litres (Mean)
Fulvestrant	0.65

Percentage of Participants With Baseline Vaginal Bleeding Who Experienced ≥50% Reduction in the Number of Vaginal Bleeding Days

Percentage of participants with baseline vaginal bleeding who experienced ≥50% reduction in the number of vaginal bleeding days during the 12 month treatment period compared to the 6 month baseline period. (NCT00278915)
Timeframe: 6 month pre-treatment observation period (baseline) followed by 12 month treatment period (on treatment period)

Intervention	Percentage of Participants (Number)
Fulvestrant	73.9

Percentage of Participants With Baseline Vaginal Bleeding Who Experienced Cessation of Vaginal Bleeding .

Percentage of participants with baseline vaginal bleeding who experienced cessation of vaginal bleeding for the full 12 month treatment period, based on a worst-case approach i.e. missing diary card days counted as bleeding days. (NCT00278915)
Timeframe: 6 month pre-treatment observation period (baseline) followed by 12 month treatment period (on treatment period)

Intervention	Percentage of Participants (Number)
Fulvestrant	35

Percentage of Participants With Baseline Vaginal Bleeding Who Experienced Cessation of Vaginal Bleeding Over a 6 Month Trial Period.

Percentage of participants with baseline vaginal bleeding who experienced cessation of vaginal bleeding for at least 180 consecutive days during the 12 month treatment period, based on a worst-case approach i.e. missing diary card days counted as bleeding days. (NCT00278915)
Timeframe: 6 month pre-treatment observation period (baseline) followed by 12 month treatment period (on treatment period)

Intervention	Percentage of Participants (Number)
Fulvestrant	78

Percentage of Patients With Gsα Mutation.

McCune-Albright Syndrome(MAS) is caused by an activating mutation in the gene coding for the stimulatory subunit of the G protein, Gsα. The altered Gsα causes autonomous activation of G-protein stimulated cAMP formation, which in the gonads, results in episodic uncontrolled sex steroid production and subsequent pubertal development. For patients who provided separate specific informed consent, the percentage of patients with a Gsα mutation at screening was assessed by molecular analysis. (NCT00278915)
Timeframe: Screening assessment (baseline)

Intervention	Percentage of participants (Number)
Fulvestrant	23

PK: Mean Clearance.

Mean clearance is the average amount of Fulvestrant which is eliminated (NCT00278915)
Timeframe: Throughout the 12 month treatment period.

Intervention	Litres/hour (Mean)
Fulvestrant	38.4

PK: Mean Volume of Distribution (V1/F)

Total apparent volume of distribution (Vss/F) is the total apparent volume in the body into which Fulvestrant distributes at equilibrium. Vss/F = V1/F + V2/F. V1/F is the volume of the 1st compartment and V2/F is the volume of the second compartment. V1/F only is presented here. The measure of variability presented is the inter-individual error. (NCT00278915)
Timeframe: Throughout the 12 month treatment period.

Intervention	Litres (Mean)
Fulvestrant	33000

PK: Mean Volume of Distribution (V2/F) .

Total apparent volume of distribution (Vss/F) is the total apparent volume in the body into which Fulvestrant distributes at equilibrium. Vss/F = V1/F + V2/F. V1/F is the volume of the 1st compartment and V2/F is the volume of the second compartment. V2/F only is presented here. The measure of variability presented is the inter-individual error. (NCT00278915)
Timeframe: Throughout the 12 month treatment period.

Intervention	Litres (Mean)
Fulvestrant	32700

Clinical Benefit Rate of the Combination of Enzalutamide/ Fulvestrant

To determine the clinical benefit rate at 24 weeks of the combination of enzalutamide/fulvestrant. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan or by caliper. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR; clinical benefit rate (CBR) at 24 weeks (CR + PR + stable disease lasting at least 24 weeks. (NCT02953860)
Timeframe: 24 Weeks

Intervention	Participants (Count of Participants)
Fulvestrant With Enzalutamide	7

Percent Progression Free at 24 Weeks

PFS is defined as the time from the first day of enzalutamide treatment (Study Day 1) until documented disease progression or death on study, whichever occurs first. Percent (%) progression free at 24 weeks is the number of patients without disease progression after 24 weeks follow-up. (NCT02953860)
Timeframe: Up to 24 Weeks

Intervention	Participants (Count of Participants)
Fulvestrant With Enzalutamide	7

Number of Participants With Treatment-Emergent Adverse Events (Safety Profile)

The safety of the combination of enzalutamide with fulvestrant will be assessed according to CTCAE 4.03. (NCT02953860)
Timeframe: 24 Weeks

Intervention	participants (Number)
	fatigue	nausea	vomiting	constipation	headache	diarrhea	cognitive dysfunction
Fulvestrant With Enzalutamide	17	16	9	10	11	7	5

Clinical Benefit Rate (CBR)

CBR was defined as the percentage of participants with measurable disease at baseline achieving complete response (CR), partial response (PR), or stable disease (SD) for 24 weeks or longer based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PD is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions. Stable disease (SD) is defined as any condition not meeting the above criteria. SD needed to be a minimum 24 weeks in duration. (NCT01560416)
Timeframe: Disease was assessed radiographically every 2 cycles for year 1 and every 2-4 cycles thereafter on treatment. Maximum treatment duration was 41 cycles (Arm A) and 42 cycles (Arm B) which approximates 38 months.

Intervention	percentage of participants (Number)
ARM A - Fulvestrant	33.3
Arm B - Fulvestrant+Ganetespib	34.3

Grade 3-4 Toxicity Rate

All grade 3-4 adverse events (AE) with treatment attribution of possibly, probably or definite based on NCI Common Toxicity Criteria for Adverse Events version 4 (CTCAEv4) as reported on case report forms were counted to calculate the percentage of participants experiencing at least one treatment-related grade 3 or 4 AE of any type on treatment. (NCT01560416)
Timeframe: AEs were assessed every cycle on treatment (weeks 2-3 on cycle 1). Median treatment duration was 4 cycles/~4 months on each arm. Maximum treatment duration was 41 cycles (Arm A) and 42 cycles (Arm B) which approximates 38 months.

Intervention	percentage of participants (Number)
ARM A - Fulvestrant	100
Arm B - Fulvestrant+Ganetespib	100
Arm A - Crossover Fulvestrant+Ganetespib	100

Objective Response Rate (ORR)

ORR was defined as the percentage of participants with measurable disease at baseline achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. (NCT01560416)
Timeframe: Disease was assessed radiographically every 2 cycles for year 1 and every 2-4 cycles thereafter on treatment. Maximum treatment duration was 41 cycles (Arm A) and 42 cycles (Arm B) which approximates 38 months.

Intervention	percentage of participants (Number)
ARM A - Fulvestrant	20.0
Arm B - Fulvestrant+Ganetespib	14.3

Overall Survival (OS)

OS based on Kaplan-Meier is defined as the time from study entry to death or date last known alive or censored at date last known alive. (NCT01560416)
Timeframe: Participants were followed long-term for survival every 3 months from the end of treatment until death, lost to follow-up or up to 4 years from treatment end. Median survival follow-up was 28 months for the study cohort.

Intervention	months (Median)
ARM A - Fulvestrant	25.9
Arm B - Fulvestrant+Ganetespib	29.2

Progression-Free Survival (PFS)

PFS based on Kaplan-Meier is defined as the time from study entry to the earliest documentation of disease progression (PD) or death. Participants alive without evidence of PD are censored at the date of last disease assessment. Participants who receive non-protocol anti-cancer therapy before disease progression are censored at time of last disease assessment. (NCT01560416)
Timeframe: Disease was assessed radiographically every 2 cycles for year 1 and every 2-4 cycles longer-term. Participants in this study cohort were followed for survival up to 4 years from treatment end.

Intervention	months (Mean)
ARM A - Fulvestrant	3.7
Arm B - Fulvestrant+Ganetespib	3.6

Clinical Benefit Rate

A clinical benefit (CB) responder is defined as a patient having a best overall response of either CR, PR or SD for at least 24 weeks per RECIST v1.1. As tumour assessments can occur ± 2 weeks of the specified time point, the CBR is defined as the proportion of patients in the FAS who have CB ≥ 22 weeks (or 154 days). (NCT01300351)
Timeframe: 36 months

Intervention	patients (Number)
Fulvestrant 500 mg	53
Fulvestrant 250 mg	36

Duration of Clinical Benefit

"Duration of clinical benefit (DoCB) will be evaluated only for patients who have CB, and is defined as the time from the date of randomisation until the date of disease progression or death from any cause, whichever is earlier.~Any patient who has not progressed or died by the date of DCO or who has been lost to follow up will be right censored at the date of their last evaluable disease assessment." (NCT01300351)
Timeframe: 36 months

Intervention	months (Median)
Fulvestrant 500 mg	14.3
Fulvestrant 250 mg	13.8

Duration of Response

"Duration of response (DoR) will be evaluated only for patients who have an objective response, and is defined as the time from the date of first documentation of objective response (i.e., the initial visit at which CR or PR was recorded) until the date of disease progression or death due to any cause (whichever is earlier). The time of the initial response will be defined as the latest of the dates contributing towards the first visit response of PR or CR.~Any patient who has not progressed or died by the date of DCO, or who has been lost to follow up, will be right-censored at the date of their last disease assessment." (NCT01300351)
Timeframe: 36 months

Intervention	months (Median)
Fulvestrant 500 mg	16.6
Fulvestrant 250 mg	22.2

Objective Response Rate

The ORR is defined as the proportion of all randomized patients with measurable disease at baseline who have a best objective tumour response of either CR or PR per RECIST v1.1. (NCT01300351)
Timeframe: 36 months

Intervention	patients (Number)
Fulvestrant 500 mg	16
Fulvestrant 250 mg	11

Progression-free Survival

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, or unequivocal progression of existing non-target lesions, or the appearance of new lesions, or death (by any cause in the absence of progression). The primary analysis for PFS was the log rank test stratified by last endocrine therapy received prior to fulvestrant (AO vs. AI). The treatment effect was estimated using the HR of 500 mg fulvestrant to 250 mg fulvestrant together with the corresponding 95% CI and p value. (NCT01300351)
Timeframe: 36 months

Intervention	months (Median)
Fulvestrant 500 mg	8.0
Fulvestrant 250 mg	4.0

Number of Participants With Adverse Events as a Measure of Safety

"The type, frequency and severity of adverse events, laboratory values, and Electrocardiograms (ECGs) experienced by patients will be assessed according to Common Terminology Criteria for Adverse Events.~The study enrollment was terminated early due to challenges in enrolling patients with FGF amplified status. See safety section for safety details." (NCT01528345)
Timeframe: Screening, Week 2, Week 4 and approximately every 4 weeks during treatment period (approximately 34 months)

Intervention	Participants (Number)
Fulvestrant + Dovitinib Active	47
Fulvestrant + Dovitinib Placebo	50

Overall Survival (OS) Using Kaplan- Meier Method

OS was defined as the time from the date of randomization to the date of death from any cause. If a patient is not known to have died at the date of analysis cut-off, the OS will be censored at the last date of contact. (NCT01528345)
Timeframe: From date of randomization to date of death from any cause whichever comes first, assessed up to 34 months

Intervention	Months (Median)
Fulvestrant + Dovitinib Active	NA
Fulvestrant + Dovitinib Placebo	25.9

Overall Response Rate (ORR)

ORR was defined as the percentage of patients with a best overall response of Complete Response (CR) or Partial Response (PR) as per RECIST v1.1. Responses include: Complete Response: Disappearance of all non-nodal target lesions; Partial Response: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters; Progressive Disease: At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline; Stable Disease: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD; Unknown (UNK) Progression has not been documented and one or more target lesions have not been assessed or have been assessed using a different method than baseline. (NCT01528345)
Timeframe: Every 8 weeks assessed up to 34 months

Intervention	Percentage of participants (Number)
	All patients	FGF amplified patients	FGF non-amplified patients
Fulvestrant + Dovitinib Active	27.7	20.0	31.3
Fulvestrant + Dovitinib Placebo	10.0	12.5	8.8

Progression Free Survival (PFS) Based on Local Investigator Assessment

PFS was defined as the time from the date of randomization to the date of the first radiologically documented disease progression or death due to any cause and was assessed based on RECIST v1.1. Responses include: Complete Response: Disappearance of all non-nodal target lesions; Partial Response: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters; Progressive Disease: At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline; Stable Disease: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD; Unknown (UNK) Progression has not been documented and one or more target lesions have not been assessed or have been assessed using a different method than baseline. (NCT01528345)
Timeframe: Every 8 weeks assessed up to 34 months

Intervention	Months (Median)
	All patients (n: 30, 34)	FGF amplified patients (n: 9, 9)	FGF non-amplified patients (n: 21, 25)
Fulvestrant + Dovitinib Active	5.5	10.9	5.5
Fulvestrant + Dovitinib Placebo	5.5	5.5	5.5

Number of Participants Experiencing Dose Limiting Toxicities (DLTs)

A DLT was a toxicity, considered possibly related to alobresib, and which occurred during DLT assessment window (Day 1 through Cycle 1 Day 28) in each cohort: Grade ≥ 4 neutropenia (absolute neutrophil count [ANC] < 500/mm^3); Grade ≥3 neutropenia (ANC< 1000/mm^3) with fever (a single temperature of > 38.3°C or a sustained temperature of ≥ 38°C for more than 1 hour [hr]); Grade ≥ 3 thrombocytopenia; Grade ≥ 2 bleeding; Grade ≥ 3 non hematologic toxicity, except Grade 3 nausea or emesis with maximum duration of 48 hrs on adequate medical therapy and Grade 3 diarrhea which persists for < 72 hrs in absence of maximal medical therapy; Grade ≥ 2 non hematologic treatment-emergent adverse event (TEAE) of potential clinical significance; treatment interruption ≥ 7 days due to unresolved toxicity; and any Grade 3 or 4 elevation in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) associated with a Grade 2 elevation in bilirubin that is at least possibly related to alobresib. (NCT02392611)
Timeframe: Baseline (Day 1) up to 28 days

Intervention	Participants (Count of Participants)
Monotherapy: Alobresib 0.6 mg	0
Monotherapy: Alobresib 1.4 mg	0
Monotherapy: Alobresib 2 mg	0
Monotherapy: Alobresib 3 mg	1
Monotherapy: Alobresib 4 mg	1
Monotherapy: Alobresib 6 mg	2
Combination Therapy: Alobresib 2 mg + Exemestane	0
Combination Therapy: Alobresib 2 mg + Fulvestrant	0
Combination Therapy: Alobresib 3 mg + Fulvestrant	1

PK Parameter: AUCtau of Alobresib

AUCtau is defined as the concentration of drug over time (the area under the concentration verses time curve over the dosing interval). (NCT02392611)
Timeframe: Cycle 1: Predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hrs postdose on Day 8 (1 Cycle = 28 days)

Intervention	h*ng/mL (Mean)
Monotherapy: Alobresib 0.6 mg	643.3
Monotherapy: Alobresib 1.4 mg	1838.5
Monotherapy: Alobresib 2 mg	1591.8
Monotherapy: Alobresib 3 mg	4391.7
Monotherapy: Alobresib 4 mg	4128.5
Monotherapy: Alobresib 6 mg	9373.8
Combination Therapy: Alobresib 2 mg + Exemestane	1750.8
Combination Therapy: Alobresib 2 mg + Fulvestrant	2514.3
Combination Therapy: Alobresib 3 mg + Fulvestrant	5644.0

PK Parameter: Ctau of Alobresib

Ctau is defined as the observed drug concentration at the end of the dosing interval. (NCT02392611)
Timeframe: Cycle 1: Predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hrs postdose on Day 8 (1 Cycle = 28 days)

Intervention	ng/mL (Mean)
Monotherapy: Alobresib 0.6 mg	14.7
Monotherapy: Alobresib 1.4 mg	60.7
Monotherapy: Alobresib 2 mg	34.4
Monotherapy: Alobresib 3 mg	131.0
Monotherapy: Alobresib 4 mg	168.4
Monotherapy: Alobresib 6 mg	237.1
Combination Therapy: Alobresib 2 mg + Exemestane	44.2
Combination Therapy: Alobresib 2 mg + Fulvestrant	59.4
Combination Therapy: Alobresib 3 mg + Fulvestrant	170.0

Pharmacokinetic (PK) Parameter: Cmax of Alobresib

Cmax is defined as the maximum concentration of the drug. (NCT02392611)
Timeframe: Cycle 1: Predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hrs postdose on Days 1 and 8 (1 Cycle = 28 days)

,,,,,,,,

Intervention	ng/mL (Mean)
	Cycle 1 Day 1	Cycle 1 Day 8
Combination Therapy: Alobresib 2 mg + Exemestane	160.8	193.0
Combination Therapy: Alobresib 2 mg + Fulvestrant	149.7	278.0
Combination Therapy: Alobresib 3 mg + Fulvestrant	234.3	458.7
Monotherapy: Alobresib 0.6 mg	35.2	64.0
Monotherapy: Alobresib 1.4 mg	59.1	117.0
Monotherapy: Alobresib 2 mg	141.0	174.0
Monotherapy: Alobresib 3 mg	197.5	296.5
Monotherapy: Alobresib 4 mg	281.7	407.2
Monotherapy: Alobresib 6 mg	376.2	711.5

PK Parameter: AUC0-24 of Alobresib

AUC0-24 is defined as the concentration of drug over time from time zero to time 24 hrs. (NCT02392611)
Timeframe: Cycle 1: Predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hrs postdose on Days 1 and 8 (1 Cycle = 28 days)

,,,,,,,,

Intervention	h*ng/mL (Mean)
	Cycle 1 Day 1	Cycle 1 Day 8
Combination Therapy: Alobresib 2 mg + Exemestane	1549.0	1752.6
Combination Therapy: Alobresib 2 mg + Fulvestrant	1900.9	2525.7
Combination Therapy: Alobresib 3 mg + Fulvestrant	3038.5	5665.1
Monotherapy: Alobresib 0.6 mg	699.5	640.0
Monotherapy: Alobresib 1.4 mg	1896.1	1838.5
Monotherapy: Alobresib 2 mg	1413.2	1603.3
Monotherapy: Alobresib 3 mg	2336.1	4430.5
Monotherapy: Alobresib 4 mg	2692.1	5584.5
Monotherapy: Alobresib 6 mg	6347.4	9432.2

PK Parameter: t1/2 of Alobresib

t1/2 is defined as the estimate of the terminal elimination half-life of the drug. Due to short sampling period of the terminal elimination phase in these cohorts t1/2 values should be interpreted with caution. (NCT02392611)
Timeframe: Cycle 1: Predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hrs postdose on Days 1 and 8 (1 Cycle = 28 days)

,,,,,,,,

Intervention	hour (Median)
	Cycle 1 Day 1	Cycle 1 Day 8
Combination Therapy: Alobresib 2 mg + Exemestane	13.5	14.0
Combination Therapy: Alobresib 2 mg + Fulvestrant	23.4	22.0
Combination Therapy: Alobresib 3 mg + Fulvestrant	15.2	22.3
Monotherapy: Alobresib 0.6 mg	16.6	13.7
Monotherapy: Alobresib 1.4 mg	35.3	28.7
Monotherapy: Alobresib 2 mg	15.8	15.9
Monotherapy: Alobresib 3 mg	20.2	16.8
Monotherapy: Alobresib 4 mg	19.2	16.1
Monotherapy: Alobresib 6 mg	21.1	17.8

PK Parameter: Tmax of Alobresib

Tmax is defined as the time (observed time point) of Cmax. (NCT02392611)
Timeframe: Cycle 1: Predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hrs postdose on Days 1 and 8 (1 Cycle = 28 days)

,,,,,,,,

Intervention	hour (Median)
	Cycle 1 Day 1	Cycle 1 Day 8
Combination Therapy: Alobresib 2 mg + Exemestane	0.5	0.5
Combination Therapy: Alobresib 2 mg + Fulvestrant	6.1	0.5
Combination Therapy: Alobresib 3 mg + Fulvestrant	1.1	0.5
Monotherapy: Alobresib 0.6 mg	2.1	1.3
Monotherapy: Alobresib 1.4 mg	4.0	0.6
Monotherapy: Alobresib 2 mg	0.5	0.5
Monotherapy: Alobresib 3 mg	2.0	1.0
Monotherapy: Alobresib 4 mg	0.5	0.9
Monotherapy: Alobresib 6 mg	4.1	0.8

PSA Doubling Time

Number of subjects with prolongation of PSA doubling time (NCT00476645)
Timeframe: 3 months

Intervention	participants (Number)
Fulvestrant 250 mg	3

PSA Reduction ≥ 50%

Number of subjects with serum PSA reduction ≥ 50% at 3 months (NCT00476645)
Timeframe: 3 months

Intervention	participants (Number)
Fulvestrant 250 mg	0

Stable Disease After One Year

Stable disease was defined as continuing treatment without disease progression, with disease progression defined as 3 consecutive rises in serum PSA or objective progression by RECIST criteria. (NCT00476645)
Timeframe: 12 months

Intervention	participants (Number)
Fulvestrant 250 mg	1

Clinical Benefit Rate (CBR)

CBR was defined as the percentage of participants who achieved a best response of CR, PR, or stable disease (SD) of any duration. CR was defined as disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. (NCT02756364)
Timeframe: Up to 40 months

Intervention	percentage of participants (Number)
Arm A: Fulvestrant 500 mg	60.9
Arm B: Fulvestrant 500 mg + Sapanisertib 4 mg QD	74.5
Arm C: Fulvestrant 500 mg + Sapanisertib 30 mg QW	66.0

Objective Response Rate (ORR)

ORR was defined as the percentage of participants who achieve a best response of complete response (CR) or partial response (PR) according to RECIST v1.1 criteria. CR was defined as disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions. (NCT02756364)
Timeframe: Up to 40 months

Intervention	percentage of participants (Number)
Arm A: Fulvestrant 500 mg	10.9
Arm B: Fulvestrant 500 mg + Sapanisertib 4 mg QD	21.3
Arm C: Fulvestrant 500 mg + Sapanisertib 30 mg QW	12.8

Overall Survival (OS)

OS was defined as the time from the date of randomization to the date of death. (NCT02756364)
Timeframe: Up to 164 weeks

Intervention	months (Median)
Arm A: Fulvestrant 500 mg	30.5
Arm B: Fulvestrant 500 mg + Sapanisertib 4 mg QD	NA
Arm C: Fulvestrant 500 mg + Sapanisertib 30 mg QW	34.2

Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE)

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. (NCT02756364)
Timeframe: Up to 164 weeks

Intervention	percentage of participants (Number)
Arm A: Fulvestrant 500 mg	89.1
Arm B: Fulvestrant 500 mg + Sapanisertib 4 mg QD	100.0
Arm C: Fulvestrant 500 mg + Sapanisertib 30 mg QW	100.0

Progression Free Survival (PFS)

PFS was defined as the time from the date of randomization to the date of first documentation of progressive disease (PD) or death due to any cause, whichever occurred first. Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. (NCT02756364)
Timeframe: Up to 40 months

Intervention	months (Median)
Arm A: Fulvestrant 500 mg	3.5
Arm B: Fulvestrant 500 mg + Sapanisertib 4 mg QD	7.2
Arm C: Fulvestrant 500 mg + Sapanisertib 30 mg QW	5.6

Time to Progression (TTP)

TTP was defined as the time from the date of randomization to the date of first documentation of progression. Per RECIST v1.1, PD was defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. (NCT02756364)
Timeframe: Up to 40 months

Intervention	months (Median)
Arm A: Fulvestrant 500 mg	3.5
Arm B: Fulvestrant 500 mg + Sapanisertib 4 mg QD	7.2
Arm C: Fulvestrant 500 mg + Sapanisertib 30 mg QW	5.6

Percentage Change From Baseline to Time of Surgery in Ki67 Labelling Index: Antitumour Effects of Fulvestrant, Anastrozole and a Combination of Both as Measured by the Ki67 Labelling Index.

For each sample, the Ki67 labelling index is calculated as the percentage of cells stained positive for Ki67. Range 0-100. The greater the change from baseline (randomization) in Ki67 labelling index, the greater the blockage of Ki67 expression and the greater the potential anti-tumour activity. Percentage change from baseline=[(SRG - BL)/BL]x100 (NCT00259090)
Timeframe: Surgery (SRG) was to be performed between days 15 and 22 after baseline (BL)

Intervention	Percentage change from baseline (Mean)
Fulvestrant	-62
Fulvestrant + Anastrozole	-68
Anastrozole	-75

Percentage Change From Baseline to Time of Surgery in Oestrogen Receptor (ER) H-score: Antitumour Effects of Fulvestrant, Anastrozole and a Combination of Both as Measured by the ER H-score.

For each sample, the ER H-score is calculated from the percentage of cells staining very weak (+/-); weak (+); moderate (++); or strong (+++) as follows: H-score = [(0.5 x percent +/-) + (1 x percent +) + (2 x percent ++) + (3 x percent +++)]. Range 0-300. The greater the change from baseline (randomization) in ER H-score, the greater the blockage of ER expression and the greater the potential anti-tumour activity. Percentage change from baseline=[(SRG - BL)/BL]x100 (NCT00259090)
Timeframe: Surgery (SRG) was to be performed between days 15 and 22 after baseline (BL)

Intervention	Percentage change from baseline (Mean)
Fulvestrant	-37
Fulvestrant + Anastrozole	-38
Anastrozole	-7

Percentage Change From Baseline to Time of Surgery in Progesterone Receptor (PgR) H-score: Antitumour Effects of Fulvestrant, Anastrozole and a Combination of Both as Measured by the PgR H-score.

For each sample, the PgR H-score is calculated from the percentage of cells staining very weak (+/-); weak (+); moderate (++); or strong (+++) as follows: H-score = [(0.5 x percent+/-) + (1 x percent+) + (2 x percent++) + (3 x percent+++)]. Range 0-300. The greater the change from baseline (randomization in PgR H-score, the greater the blockage of PgR expression and the greater the potential anti-tumour activity. Percentage change from baseline=[(SRG - BL)/BL]x100 (NCT00259090)
Timeframe: Surgery (SRG) was to be performed between days 15 and 22 after baseline (BL)

Intervention	Percentage change from baseline (Mean)
Fulvestrant	-31
Fulvestrant + Anastrozole	-38
Anastrozole	-38

Progression-free Survival (PFS) Per Investigator Assessment in the PIK3CA Mutant Cohort

PFS, defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS will be assessed via a local radiology assessment according to RECIST 1.1 (NCT02437318)
Timeframe: Once approximately 243 PFS events in this cohort had been observed, up to 32 months

Intervention	Months (Median)
Alpelisib qd + Fulvestrant	11.0
Placebo qd + Fulvestrant	5.7

Clinical Benefit Rate

Clinical Benefit Rate (CBR), for those with evaluable disease, defined as the percentage of patients who achieved complete response, partial response and stable disease. RECIST 1.1 was used as the standard way to measure response to treatment. The mean (SD) of specific metabolites were calculated at each time point and graphically assess these measures over time with clinical response and hematological toxicity. The mean change in these variables from baseline to each follow-up point was be calculated. Generalized linear model was utilized for the correlative analysis of clinical response and hematologic events. (NCT02692755)
Timeframe: 24 weeks

Intervention	Participants (Count of Participants)
Single ARM	23

Dose Delays in Palbociclib Attributed to Neutropenia

Number of patients who required dose delays in palbociclib attributed to neutropenia. (NCT02692755)
Timeframe: 12 months

Intervention	Participants (Count of Participants)
Single ARM	17

Dose Reductions in Palbociclib Therapy Attributed to Neutropenia

Number of patients who required dose reductions in palbociclib therapy (NCT02692755)
Timeframe: 12 months

Intervention	Participants (Count of Participants)
Single ARM	13

Number of Patients Who Complete Planned Oncologic Therapy Without the Development of a Hematological Event

"For study purpose febrile neutropenia will be defined according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0: ANC less than 1000/mm3 with a single temperature of >38.3 degrees Celsius (101 degrees Fahrenheit) or a sustained temperature of 38 degrees Celsius (100.4 degrees Fahrenheit) for more than one hour.~Planned oncology therapy is defined as completion of one year of therapy for advanced breast cancer in the absence of disease progression or cessation of study drug due to progressive disease or non-hematological toxicity." (NCT02692755)
Timeframe: 12 months

Intervention	Participants (Count of Participants)
Palbociclib + Letrozole or Fulvestrant	35

Clinical Benefit Rate (CBR) for Fulvestrant Treatment Versus Anastrozole Treatment

CBR was defined as the percentage of patients who had a clinical benefit (i.e. best objective response of CR, PR or stable disease), that was maintained for at least 24 weeks, prior to any evidence of progression. Note that a minimum duration of 22 weeks for CBR was applicable in the analysis (rather than 24 weeks) to allow for the protocolled window of +/-2 weeks. (NCT01602380)
Timeframe: Baseline RECIST 1.1 assessments and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months for the primary analysis data cut-off).

Intervention	Percentage of participants (Number)
Fulvestrant 500 mg	78.3
Anastrozole 1 mg	74.1

Comparison of Overall Survival (OS) in Patients Treated With Fulvestrant With Those Treated With Anastrozole; Percentage of Patients With Events

OS was defined as the time from randomisation until death by any cause. Two timepoints were planned for OS analysis: an interim OS analysis at the time of the data cut-off for PFS analysis and a final OS analysis when 75% of the deaths have occurred. The current OS data correspond to that of the interim analysis only and the outcome measure is reported as percentage of patients with events. (NCT01602380)
Timeframe: Baseline up to data cut-off for PFS analysis (up to approximately 38 months). Following disease progression, patients were to be contacted at 12 weekly intervals to to determine survival status.

Intervention	Percentage of participants (Number)
Fulvestrant 500 mg	29.1
Anastrozole 1 mg	32.3

Comparison of Progression Free Survival (PFS) in Patients Treated With Fulvestrant With Those Treated With Anastrozole

PFS was defined as the time from randomisation until objective disease progression according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1), surgery or radiotherapy to manage worsening of disease or death by any cause (in the absence of progression). Outcome measure is reported as median time from randomisation to PFS, calculated using the Kaplan-Meier technique. (NCT01602380)
Timeframe: Baseline RECIST 1.1 assessments and then every 12 weeks until the earliest of disease progression evident, patient dies or has surgery/radiotherapy for their disease (up to approximately 38 months for the primary analysis data cut-off).

Intervention	Months (Median)
Fulvestrant 500 mg	16.6
Anastrozole 1 mg	13.8

Duration of Clinical Benefit (DoCB) for Fulvestrant Treatment Versus Anastrozole Treatment

DoCB was defined only for patients who had clinical benefit, as the time in days from date of randomisation until the date of disease progression. (NCT01602380)
Timeframe: Baseline RECIST 1.1 assessments and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months for the primary analysis data cut-off).

Intervention	Months (Median)
Fulvestrant 500 mg	22.1
Anastrozole 1 mg	19.1

Duration of Response (DoR) for Fulvestrant Treatment Versus Anastrozole Treatment

DoR was defined only for patients who had an objective response, as the time in days from date of first documentation of response (CR/PR) until date of disease progression. (NCT01602380)
Timeframe: Baseline RECIST 1.1 assessments and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months for the primary analysis data cut-off)..

Intervention	Months (Median)
Fulvestrant 500 mg	20.0
Anastrozole 1 mg	13.2

Expected Duration of Clinical Benefit (EDoCB) for Fulvestrant Treatment Versus Anastrozole Treatment

EDoCB was estimated using the formula EDoCB = p Efp(x), where x = EDoCB, p = proportion of responders, and Efp(x) = mean duration of response for responders. The estimation was completed by using the maximum likelihood estimates of p and Efp(x), as described by Ellis (Ellis S et al. Analysis of duration of response in oncology trials, Contemp Clin Trials 2008; 29:456-65). (NCT01602380)
Timeframe: Baseline RECIST 1.1 assessments and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months for the primary analysis data cut-off).

Intervention	Days (Number)
Fulvestrant 500 mg	667.94
Anastrozole 1 mg	532.04

Expected Duration of Response (EDoR) for Fulvestrant Treatment Versus Anastrozole Treatment

EDoR was estimated using the formula EDoR = p Efp(x), where x = DoR, p = proportion of responders, and Efp(x) = mean duration of response for responders. The estimation was completed by using the maximum likelihood estimates of p and Efp(x), as described by Ellis (Ellis S et al. Analysis of duration of response in oncology trials, Contemp Clin Trials 2008; 29:456-65). (NCT01602380)
Timeframe: Baseline RECIST 1.1 assessments and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months for the primary analysis data cut-off).

Intervention	Days (Number)
Fulvestrant 500 mg	346.84
Anastrozole 1 mg	227.58

Objective Response Rate (ORR) for Fulvestrant Treatment Versus Anastrozole Treatment

ORR was defined as the percentage patients with an objective response (i.e. those recording a partial response [PR] or complete response [CR]) at some point during the study, prior to disease progression. ORR was assessed in patients with measurable disease at baseline only. The determination of measurable disease at baseline was done using baseline RECIST data. (NCT01602380)
Timeframe: Baseline RECIST 1.1 assessments and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months for the primary analysis data cut-off).

Intervention	Percentage of participants (Number)
Fulvestrant 500 mg	46.1
Anastrozole 1 mg	44.9

Comparison of the Effect of Fulvestrant Treatment Versus Anastrozole Treatment on Time to Deterioration of Health Related Quality of Life (HRQoL)

The Functional Assessment of Cancer Therapy - Breast (FACT-B) questionnaire was the instrument selected to assess HRQoL and comprises the following subscales: physical well-being (PWB), functional well-being (FWB), social well-being, emotional well-being, and breast cancer subscale (BCS). The main outcome measure from the FACT-B questionnaire was the Trial Outcome Index (TOI), which was a summary of the following subscales: PWB, FWB, and BCS. Outcome measure is reported as median time to deterioration, defined as the interval from the date of randomisation to the first assessment of worsened without an improvement in the next 12 weeks in FACT-B TOI, or the date of death (by any cause in the absence of symptom deterioration). Time to deterioration as measured by FACT-B total score was derived similarly and is also reported. (NCT01602380)
Timeframe: Quality of life questionnaires completed at baseline and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months for the primary analysis data cut-off).

Intervention	months (Median)
	Time to TOI deterioration	Time to FACT-B total score deterioration
Anastrozole 1 mg	11.1	11.1
Fulvestrant 500 mg	13.8	13.8

Overall Survival

Overall Survival (OS) is defined as the time from the date of randomization to the date of death from any cause. The study was terminated on 30 Nov 2018 . Data represents outcomes up to 150 days of treatment. (NCT03241810)
Timeframe: Randomization until death due to any cause up to 13 months (The study terminated prematurely)

Intervention	participants (Number)
Arm A (Experimental): Seribantumab and Fulvestrant	1
Arm B (Control): Placebo and Fulvestrant	1

Progression Free Survival

"Progression Free Survival is defined as the time from randomization to the first documented radiographical progression of disease using RECIST v1.1 or death from any cause, whichever comes first as assessed by the investigator.~The tumor assessment (i.e., scan dates) was used for progression/censor date not the date corresponding to the determination of overall response. Progression-free survival time distribution and median survival for each treatment group were analyzed using the Kaplan-Meier method." (NCT03241810)
Timeframe: Randomization until progression of disease or death due to any cause up to 13 months (The study terminated prematurely) . The primary analysis was planned to be initiated when 58 PFS events have occurred

Intervention	Participants (Number)
Arm A (Experimental): Seribantumab and Fulvestrant	1
Arm B (Control): Placebo and Fulvestrant	1

Time to Progression

Time to Progression (TTP) is defined as the time from the date of randomization to the date of objective tumor progression. (NCT03241810)
Timeframe: Randomization to date of objective tumor progression up to 13 months (The study terminated prematurely)

Intervention	days (Median)
Arm A (Experimental): Seribantumab and Fulvestrant	52
Arm B (Control): Placebo and Fulvestrant	48

Number of Participants With Treatment-emergent Adverse Events Reported With the Combinations of Seribantumab Plus Fulvestrant Versus Fulvestrant Alone

Treatment-emergent adverse events (TEAEs) are defined as any event that occurred after the first dose of study drug and was not present prior to study drug administration or worsened in severity after study drug administration. (NCT03241810)
Timeframe: TEAEs were collected through the study completion (30 Nov 2018), up to 13 months. Frequency and percent summaries were presented for TEAE defined as adverse events that occur or worsen in severity following the first dose of seribantumab, or fulvestrant

Intervention	participants (Number)
	Patients with any TEAE-Related	Patients with any TEAE-Serious Adverse event	NCI-CTCAE Grade 3 or Higher
Arm A (Experimental): Seribantumab and Fulvestrant	7	1	2
Arm B (Control): Placebo and Fulvestrant	4	0	1

Percentage of Treatment-emergent Adverse Events Reported With the Combinations of Seribantumab Plus Fulvestrant Versus Fulvestrant Alone

Intervention	percentage of adverse events (Number)
	TEAE-Related	TEAE-Serious Adverse event	NCI-CTCAE Grade 3 or Higher
Arm A (Experimental): Seribantumab and Fulvestrant	63.6	9.1	18.2
Arm B (Control): Placebo and Fulvestrant	36.4	0	9.1

Change From Baseline in Health Status Using the EuroQol 5-Dimension 5 Level (EQ-5D 5L)

European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a standardized measure of health status of the participant. The EQ-5D-5L is assessed using a visual analog scale (VAS) that ranged from 0 to 100mm, where 0 is the worst health you can imagine and 100 is the best health you can imagine. A higher score indicates better health state. LS Mean value was controlled for Treatment, visit, Treatment*Visit and baseline. (NCT02107703)
Timeframe: Baseline, End of Study (Up To 31 Months)

Intervention	mm (Least Squares Mean)
Abemaciclib + Fulvestrant	0.12
Placebo + Fulvestrant	1.16

Change From Baseline in Pain and Symptom Burden Assessment Using the Modified Brief Pain Inventory-Short Form (mBPI-sf)

A self-reported scale that measures the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). The overall change is based on the estimated main treatment effect. Least square (LS) Mean value was controlled for Treatment, visit, Treatment*Visit and baseline. (NCT02107703)
Timeframe: Baseline, End of Study (Up To 31 Months)

Intervention	score on a scale (Least Squares Mean)
Abemaciclib + Fulvestrant	-0.06
Placebo + Fulvestrant	0.00

Duration of Response (DOR)

DOR was the time from the date of first evidence of complete response or partial response to the date of objective progression or the date of death due to any cause, whichever is earlier. CR and PR were defined using the RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. If a responder was not known to have died or have objective progression as of the data inclusion cutoff date, duration of response was censored at the last adequate tumor assessment date. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. (NCT02107703)
Timeframe: From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up To 31 Months)

Intervention	Months (Median)
Abemaciclib + Fulvestrant	NA
Placebo + Fulvestrant	25.6

Overall Survival (OS)

OS defined as the time from the date of randomization to the date of death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive. The final analysis of the OS outcome was conducted after 440 OS events had been observed. (NCT02107703)
Timeframe: From Date of Randomization until Death Due to Any Cause (Up To 72 Months)

Intervention	Months (Median)
Abemaciclib + Fulvestrant	45.80
Placebo + Fulvestrant	37.25

Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])

ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. (NCT02107703)
Timeframe: From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 Months)

Intervention	Percentage of participants (Number)
Abemaciclib + Fulvestrant	35.2
Placebo + Fulvestrant	16.1

Percentage of Participants Achieving CR, PR or Stable Disease (SD) (Disease Control Rate [DCR])

Disease Control Rate (DCR) was the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. (NCT02107703)
Timeframe: From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 Months)

Intervention	Percentage of participants (Number)
Abemaciclib + Fulvestrant	83.0
Placebo + Fulvestrant	75.8

Percentage of Participants With CR, PR or SD With a Duration of At Least 6 Months (Clinical Benefit Rate [CBR])

Clinical benefit rate defined as percentage of participants with best overall response of CR, PR, or SD with a duration of at least 6 months.CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions.PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions.SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. Percentage of participants=(participants with CR+PR+SD with a duration of at least 6 months /number of participants enrolled) *100.PD was at least a 20% increase in sum of the diameters of target lesions,with reference being the smallest sum on study and an absolute increase of at least 5 mm or unequivocal progression of non-target lesions,or 1 or more new lesions. (NCT02107703)
Timeframe: From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 Months)

Intervention	Percentage of participants (Number)
Abemaciclib + Fulvestrant	72.2
Placebo + Fulvestrant	56.1

Progression-Free Survival (PFS)

PFS defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of randomization, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date. (NCT02107703)
Timeframe: From Date of Randomization until Disease Progression or Death Due to Any Cause (Up To 31 Months)

Intervention	Months (Median)
Abemaciclib + Fulvestrant	16.4
Placebo + Fulvestrant	9.3

Change From Baseline to Short Term Follow up in Quality of Life Using the EORTC QLQ-BR23 (Breast) Questionnaire

EORTC-QLQ-BR23 measured multi-item functional scales for body image, sexual functioning and future perspective and measured single item symptoms scales which assessed systemic therapy side effects, breast symptoms and arm symptoms. For functional scales, scores ranged from 0 to 100 where higher scores represented a better level of functioning. For symptoms scales, scores ranged from 0 to 100 where higher scores represented a greater degree of symptoms. LS Mean value of changing from baseline to short follow up was estimated from the mixed model that was controlled for Treatment, visit, Treatment*Visit and baseline. (NCT02107703)
Timeframe: Baseline, Short Term Follow Up (Up To 31 Months)

Intervention	Units on a scale (Least Squares Mean)
	Functional scale: Body image	Functional scale:Sexual functioning	Functional scale: Future perspective	Symptom scale: Systemic therapy side effects	Symptom scale: Breast symptoms	Symptom scale: Arm symptoms
Abemaciclib + Fulvestrant	-2.20	0.41	6.06	7.23	-2.10	-0.45
Placebo + Fulvestrant	-3.27	-1.60	10.05	6.98	-0.96	0.10

Change From Baseline to Short Term Follow up in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)

EORTC QLQ-C30 v3.0 was a self-administered questionnaire with multidimensional scales that measures 5 functional domains (physical, role, cognitive, emotional, and social), global health status, and symptom scales of fatigue, pain, nausea and vomiting, dyspnea, loss of appetite, insomnia, constipation and diarrhea, and financial difficulties. A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For functional domains and global health status, scores range from 0 to 110 with higher scores representing a better level of functioning. For symptoms scales, scores range from 0 to 100 with higher scores representing a greater degree of symptoms. LS Mean value of changing from baseline to short follow up was estimated from the mixed model that was controlled for Treatment, visit, Treatment*Visit and baseline. (NCT02107703)
Timeframe: Baseline, Short Term Follow Up (Up To 31 Months)

Intervention	units on a scale (Least Squares Mean)
	Global health status	Functional scale: Physical functioning	Functional scale: Role functioning	Functional scale: Emotional functioning	Functional scale: Cognitive functioning	Functional scale: Social functioning	Symptom scale: Fatigue	Symptom scale: Nausea and vomiting	Symptom scale: Pain	Symptom scale: Dyspnoea	Symptom scale: Insomnia	Symptom scale: Appetite loss	Symptom scale: Constipation	Symptom scale: Diarrhoea	Symptom scale: Financial difficulties
Abemaciclib + Fulvestrant	-4.57	-3.76	-4.87	2.38	-3.16	-4.62	5.01	2.81	-0.47	5.21	-0.04	2.06	-0.15	4.14	0.34
Placebo + Fulvestrant	-8.15	-7.59	-9.58	-2.44	-2.96	-4.78	7.83	6.49	4.38	5.39	3.76	6.40	3.79	2.67	2.85

Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) of Abemaciclib, Its Metabolites M2 and M20

Area Under the Plasma Concentration versus Time Curve from Time Zero to Infinity (AUC[0-∞]) was evaluated for Abemaciclib and Metabolites M2 and M20. (NCT02107703)
Timeframe: Cycle 1 Day 1 2-4 hours (h) post dose, Cycle 1 Day 15 4 and 7h post dose, Cycle 2 Day 1 pre dose and 3h post dose, Cycle 3 Day1 pre dose

Intervention	Nanogramshour/milliliters (ngh/mL) (Geometric Mean)
	Abemaciclib	M2	M20
Abemaciclib + Fulvestrant	2960	1640	2870

Clinical Benefit Rate (CBR)

CBR was defined as the percentage of patients achieving a Complete Response (CR), a Partial Response (PR) or a stabilization of the disease (SD) > 6 months: the response will be evaluated according to the RECIST criteria. In the patients without measurable disease at the baseline time, the clinical benefit will be defined as the absence of progression > 6 months. (NCT00545077)
Timeframe: Up to 2 years

Intervention	Participants (Count of Participants)
Arm A: Endocrine Therapy (ET)	124
Arm B: ET With Bevacizumab (ET-B)	146

Overall Response Rate (ORR)

ORR to treatment is reflected by a frequency table containing the data of the best overall response (Complete Response, Partial Response,Stable Disease or Progressive Disease) experienced for each patient during treatment (recorded from the start of the treatment until disease progression) per arm. (NCT00545077)
Timeframe: 2 years

Intervention	Participants (Count of Participants)
Arm A: Endocrine Therapy (ET)	32
Arm B: ET With Bevacizumab (ET-B)	58

Overall Survival (OS)

OS was defined as the time elapsed since randomization, until the time in which death occurs for any reason. The patients lost in the follow-up will be censured at the date of the last follow-up. (NCT00545077)
Timeframe: Up to 2 years

Intervention	Months (Median)
Arm A: Endocrine Therapy (ET)	51.8
Arm B: ET With Bevacizumab (ET-B)	52.1

Progression-free Survival (PFS)

PFS was defined as the time elapsed from randomization until the date in which the progression of the disease or the death for any reason (whichever occurs first) is documented. (NCT00545077)
Timeframe: Up to 2 years

Intervention	Months (Median)
Arm A: Endocrine Therapy (ET)	14.4
Arm B: ET With Bevacizumab (ET-B)	19.3

Response Duration (RD)

RD was defined as the time elapsed from when a partial or complete response is verified until the time in which progression or death occurs. (NCT00545077)
Timeframe: Up to 2 years

Intervention	Months (Median)
Arm A: Endocrine Therapy (ET)	13.32
Arm B: ET With Bevacizumab (ET-B)	17.59

Time to Treatment Failure (TTF)

TTF was defined as the time elapsed since randomization until the date the treatment is discontinued for any reason (progression disease, treatment toxicity or death). (NCT00545077)
Timeframe: Up to 2 years

Intervention	Months (Median)
Arm A: Endocrine Therapy (ET)	14.4
Arm B: ET With Bevacizumab (ET-B)	15.1

Progression-free Survival

Of the two treated patients on this trial, the records show that one patient who received Herceptin only completed 3 cycles of therapy, while the second patient who received Herceptin in combination with Faslodex completed 9 cycles of therapy. The last survival data collected from October to November 2008 showed that these two participants were alive at that time. (NCT00138125)
Timeframe: 5 years

Intervention	participants (Number)
Faslodex + Herceptin	2

Pathologic Complete Response (PCR) Rate

Pathologic complete response (PCR) rate with 4 months of neo-adjuvant combination endocrine therapy (Anastrazole and Fulvestrant). (NCT00921115)
Timeframe: 4 months

Intervention	participants (Number)
Arimidex + Faslodex	0

Percentage of Participants With Clinical Benefit (PR, CR, or Stable Disease, Lasting for At Least 24 Weeks) Assessed Using RECIST v1.1

(NCT02569801)
Timeframe: From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 25 months)

Intervention	percentage of participants (Number)
GDC-0810	16.7
Fulvestrant	31.4

Percentage of Participants With Objective Response (Partial Response [PR] Plus Complete Response [CR]) According to RECIST v1.1

Objective Response was defined as the percentage of participants who attained CR or PR. CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. (NCT02569801)
Timeframe: From Day 1 to PD or death from any cause, assessed up to end of study (up to approximately 25 months)

Intervention	percentage (Number)
GDC-0810	0
Fulvestrant	8.6

GDC-0810 Plasma Concentrations by Visit

Concentration of GDC-0810 measured in plasma after a single dose (Cycle 1 Day 1) and at steady state (Cycle 3 Day 1) (NCT02569801)
Timeframe: Predose (within 30 minutes of GDC-0810 administration) and 3 hours postdose on Day 1 of Cycles 1 and 3; Cycle length=28 days

Intervention	Nanograms per milliliter (ng/mL) (Geometric Mean)
	Cycle 1, Day 1 (3 hours post-dose)	Cycle 3, Day 1 (pre-dose)	Cycle 3, Day 1 (3 hours post-dose)
GDC-0810	6510	528	10100

Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs)

(NCT02569801)
Timeframe: From Day 1 to 28 days after last dose of study drug, assessed up to end of study (up to approximately 25 months)

Intervention	percentage of participants (Number)
	AEs	SAEs
Fulvestrant	91.4	14.3
GDC-0810	97.1	20.0

Phase 1: AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for Sapanisertib

AUC(0-24) is the area under the plasma concentration-time curve of the samples collected up to 8 hours and extrapolated up to 24 hours. (NCT02049957)
Timeframe: Cycle 1 Day 15 pre-dose and multiple timepoints (Up to 8 hours) post-dose, extrapolated to 24 hours post-dose

Intervention	h*ng/mL (Mean)
Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane	577.081
Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane	178.063
Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant	332.618
Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane	277.626

Phase 1: Terminal Elimination Half-life (T1/2) for Sapanisertib

(NCT02049957)
Timeframe: Cycle 1 Day 15 pre-dose and multiple timepoints (Up to 8 hours) post-dose

Intervention	hour (Mean)
Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane	6.639
Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane	3.161
Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant	7.777
Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane	5.370

Phase 2: Best Percent Change From Baseline in Tumor Size

(NCT02049957)
Timeframe: Baseline to Month 24

Intervention	percentage change in tumor size (Mean)
Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)	-0.46
Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)	0.96
Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Resistant)	1.76
Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)	-18.91

Phase 2: Clinical Benefit Rate at 16 Weeks (CBR-16)

CBR-16 was defined as the percentage of participants who achieved confirmed complete response (CR) or partial response (PR) of any duration or had confirmed stable disease (SD) as best response and the first 2 or more post baseline scans had PR/SD and the duration of SD was >112 days. Disease response was assessed for target lesions by computed tomography (CT) or magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. CR is disappearance of all target lesions. PR is >=30% decrease in the sum of the longest diameter of target lesions. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression (PD). (NCT02049957)
Timeframe: Week 16

Intervention	percentage of participants (Number)
Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)	44
Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)	50
Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Resistant)	23
Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)	25

Phase 2: Clinical Benefit Rate at 24 Weeks (CBR-24)

CBR-24 was defined as the percentage of participants who achieved confirmed CR or PR at any time or had confirmed SD as best response and the first 2 or more post baseline scans had PR/SD and the duration of stable disease was >168 days. Disease response was assessed for target lesions by CT or MRI according to RECIST version 1.1 guidelines. CR is disappearance of all target lesions. PR is >=30% decrease in the sum of the longest diameter of target lesions. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. (NCT02049957)
Timeframe: Week 24

Intervention	percentage of participants (Number)
Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)	28
Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)	38
Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Resistant)	23
Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)	25

Phase 2: Overall Response Rate (ORR)

ORR is defined as the percentage of participants with confirmed CR or PR as per RECIST version1.1 guidelines. CR is disappearance of all target lesions. PR is >=30% decrease in the sum of the longest diameter of target lesions. (NCT02049957)
Timeframe: Baseline then every 2 cycles from Cycles 2 through 6, and every 3 cycles thereafter in a 28-day cycle up to End of Treatment (EOT) (Up to 24 months)

Intervention	percentage of participants (Number)
Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)	7
Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)	13
Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Resistant)	0
Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)	13

Phase 2: Overall Survival (OS)

OS is the time in months from start of study treatment to date of death due to any cause. Data for the analysis of OS included the censored data at the timepoint that the participant was last known to be alive. (NCT02049957)
Timeframe: Up to 24 months

Intervention	months (Median)
Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)	15.9
Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)	20.7
Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Resistant)	14.0
Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)	13.0

Phase 2: Progression-Free Survival (PFS)

PFS is defined as the time in months from the date of first dose of study treatment to the date of the first documented disease progression or death. Disease progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; or the appearance of one or more new lesions. (NCT02049957)
Timeframe: Baseline then every 2 cycles from Cycles 2 through 6, and every 3 cycles thereafter in a 28-day cycle, then every 3 months after EOT until disease progression or death (Up to 24 months)

Intervention	months (Median)
Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)	4.1
Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)	5.5
Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Resistant)	3.3
Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)	5.4

Phase 1: AUC(0-last): Area Under the Plasma Concentration-time Curve From Time 0 to Last Extrapolated Concentration Over the Dosing Interval for Sapanisertib

AUC(0-last) is the area under the plasma concentration-time curve of the samples collected up to 8 hours and extrapolated up to last time point. (NCT02049957)
Timeframe: Cycle 1 Day 15 pre-dose and multiple timepoints (Up to 8 hours) post-dose, extrapolated to last timepoint

Intervention	h*ng/mL (Mean)
	Cycle 1 Day 2
Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant	109.496

Phase 1: AUC(0-last): Area Under the Plasma Concentration-time Curve From Time 0 to Last Extrapolated Concentration Over the Dosing Interval for Sapanisertib

,,,

Intervention	h*ng/mL (Mean)
	Cycle 1 Day 15	Cycle 1 Day 2
Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane	577.081	101.599
Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane	164.123	89.576
Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant	332.618	109.548
Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane	251.165	116.557

Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

"An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event, or a previous condition that has increased in severity or frequency since the administration of study drug.~A SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. Relationship of each AE to study drug will be determined by the Investigator." (NCT02049957)
Timeframe: First dose of study drug through 30 days after the last dose (Up to 52 months)

,,,,

Intervention	Participants (Count of Participants)
	Any AE	SAEs
Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane	6	1
Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant	6	2
Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane	3	0
Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant	3	0
Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane	6	2

Phase 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Sapanisertib

(NCT02049957)
Timeframe: Cycle 1 Day 15 and Cycle 2 Day 1 pre-dose and multiple timepoints (Up to 8 hours) post-dose

Intervention	hour (Median)
	Cycle 2 Day 1
Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant	3.500

Phase 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Sapanisertib

(NCT02049957)
Timeframe: Cycle 1 Day 15 and Cycle 2 Day 1 pre-dose and multiple timepoints (Up to 8 hours) post-dose

,,,

Intervention	hour (Median)
	Cycle 1 Day 15	Cycle 2 Day 1
Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane	3.005	2.280
Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane	0.600	0.980
Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant	1.035	1.000
Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane	2.000	2.000

Phase1: Cmax: Maximum Observed Plasma Concentration for Sapanisertib

(NCT02049957)
Timeframe: Cycle 1 Day 15 and Cycle 2 Day 1 pre-dose and multiple timepoints (Up to 8 hours) post-dose

Intervention	ng/mL (Mean)
	Cycle 2 Day 1
Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant	44.96

Phase1: Cmax: Maximum Observed Plasma Concentration for Sapanisertib

(NCT02049957)
Timeframe: Cycle 1 Day 15 and Cycle 2 Day 1 pre-dose and multiple timepoints (Up to 8 hours) post-dose

,,,

Intervention	ng/mL (Mean)
	Cycle 1 Day 15	Cycle 2 Day 1
Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane	57.72	38.68
Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane	47.40	43.47
Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant	50.90	45.30
Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane	45.37	44.68

Time to Progression (TTP) in Women With Hormone Responsive Advanced Breast Cancer Treated With Combination of Exemestane and Fulvestrant.

TTP is defined as the time from first treatment to objective evidence of progression on the basis of radiological evaluation and/or physical exam (if physical examination identifies a site of measurable disease). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions (NCT00201864)
Timeframe: Every 2 cycles up to 2 years

Intervention	months (Median)
Exemestane and Fulvestrant	6.9

Examine the Effect of Exemestane + Fulvestrant on Serum IGF-1 and IGFPB-3 Levels

(NCT00201864)
Timeframe: Prestudy, Day 7 and Day 120

Intervention	ng/mL (Mean)
	Baseline	Day 7	Day 120
IGF-1	119	141	161
IGFBP-3	4946	5273	5537

Maximum Plasma Concentration (Cmax) of Exemestane When Administered Alone and With Fulvestrant

5 mL of venous whole blood was obtained before dosing and then at 1, 2, 4, 6, 8, and 24 hours after exemestane ingestion on each of the 2 time points. (NCT00201864)
Timeframe: Day 7 and Day 120

Intervention	ng/ml (Mean)
	Exemestane Alone (Day 7)	Exemestane + Fulvestrant (Day 120)
Exemestane and Fulvestrant	20.1	21.2

Overall Clinical Benefit (Complete Response Rate, Partial Response and Stable Disease)

"Response and progression was evaluated after every 2 cycles by physical examination and imaging studies using the international RECIST criteria.~Complete Response (CR), Partial Response (PR), Overall Response Rate (ORR), Stable Disease (SD), Progressive Disease (PD). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progressive Disease (PD); PD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions; Overall Response Rate (ORR), CR+PR" (NCT00201864)
Timeframe: Every 2 cycles, up to 1 year

Intervention	patients (Number)
	CR	PR	ORR	SD ≥ 6 Mo	Overall Clinical Benefit	SD< 6 Mo	PD
Exemestane and Fulvestrant	0	3	3	17	20	8	12

Median Overall Survival (OS)

Defined as the time from date of first study treatment to date of death due to any cause. Patients who are alive will be censored at the date of last known date alive. (NCT02291913)
Timeframe: up to 3 years from first treatment

Intervention	months (Median)
Everolimus	26.7

Median Progression Free Survival (PFS)

PFS is defined as the time from Day 1 of study drug administration to disease progression as defined by RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1 criteria, or death on study. Participants who are alive and free from disease progression will be censored at the date of last radiologic tumor assessment. Participants who receive non-protocol therapy (subsequent therapy) prior to incurring an event will be censored at the date of last tumor assessment prior to the start of subsequent therapy. Participants who do not have a post-baseline tumor assessment will be censored at the date of first treatment (Day 1). (NCT02291913)
Timeframe: up to 3 years

Intervention	months (Median)
Everolimus	7.2

Median Time From First Occurrence of CR or PR to Disease Progression or Death Also Called Duration of Response (DOR)

Only those patients who achieved Complete Response or Partial Response will be included in the summaries of DOR. DOR is defined as time from first date of response of CR or PR to disease progression or death as defined by RECIST v1.1 criteria. Participants who are alive and free from disease progression will be censored at the date of last tumor assessment. Patients who receive non-protocol therapy (subsequent therapy) prior to incurring an event will be censored at the date of last tumor assessment prior to the start of subsequent therapy. A CR is the complete disappearance of all target lesions. A PR is a decrease of 30% or more of the diameter(s) of all target lesions from the baseline sum of diameters. (NCT02291913)
Timeframe: every 8 weeks until discontinuation, up to 20 months

Intervention	months (Median)
Everolimus	8.8

Number of Participants With CR, PR, or 6 Months of SD Also Called Clinical Benefit Rate (CBR)

The proportion of patients with Complete Response (CR) or Partial Response (PR) or 6 months or more of Stable Disease (SD). A CR is the complete disappearance of all target lesions. A PR is a decrease of 30% or more of the diameter(s) of all target lesions from the baseline sum of diameters. SD is not meeting the criteria for PR or a 20% increase in target lesions called Progressive Disease (PD). (NCT02291913)
Timeframe: Up to 20 months

Intervention	Participants (Count of Participants)
Everolimus	12

Number of Patients With Adverse Events (AEs) as a Measure of Safety and Tolerability

Assessments were made through analysis of the reported incidence of treatment-emergent AEs. All participants who received at least one dose of protocol treatment were followed for safety. Adverse events were collected from day of first dose to 30 days after last protocol treatment and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. (NCT02291913)
Timeframe: Up to 20 months

Intervention	Participants (Count of Participants)
Everolimus	48

Number of Patients With an Objective Response (CR or PR) Also Called the Overall Response Rate (ORR).

Defined as the number of patients with objective evidence of complete or partial response (CR or PR) using RECIST version 1.1. A CR is the complete disappearance of all target lesions. A PR is a decrease of 30% or more of the diameter(s) of all target lesions from the baseline sum of diameters. (NCT02291913)
Timeframe: every 8 weeks until discontinuation, up to 20 months

Intervention	Participants (Count of Participants)
Everolimus	2

Duration of Objective Response, as Assessed by Investigator Using RECIST v1.1 at Final Analysis

Duration of objective response: the time from the first tumor assessment that supported the participant's objective response (CR or PR, whichever was first recorded) to first documented disease progression or death due to any cause, whichever occurred first. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Disease progression: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression. (NCT02340221)
Timeframe: Time from the first occurrence of a documented objective response to the time of the first documented disease progression or death from any cause, whichever occurs earlier (up to approximately 6.2 years)

Intervention	months (Median)
Placebo+Fulvestrant	7.39
Taselisib+Fulvestrant	8.97

Duration of Objective Response, as Assessed by Investigator Using RECIST v1.1 at Primary Analysis

Intervention	months (Median)
Placebo+Fulvestrant	7.23
Taselisib+Fulvestrant	8.74

OS at Final Analysis

OS was defined as the time from the date of randomization to the date of death due to any cause. (NCT02340221)
Timeframe: From randomization up to death from any cause (up to approximately 6.2 years)

Intervention	months (Median)
Placebo+Fulvestrant	27.93
Taselisib+Fulvestrant	27.79

Overall Survival (OS) at Primary Analysis

OS was defined as the time from the date of randomization to the date of death due to any cause. (NCT02340221)
Timeframe: From randomization up to death from any cause (up to the 15 Oct 2017 data cutoff, approximately 2.5 years)

Intervention	months (Median)
Placebo+Fulvestrant	23.56
Taselisib+Fulvestrant	26.81

Percentage of Participants With Adverse Events at Final Analysis

An adverse event was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. (NCT02340221)
Timeframe: From randomization up to approximately 6.2 years

Intervention	percentage of participants (Number)
Placebo+Fulvestrant	91.1
Taselisib+Fulvestrant	97.1

Percentage of Participants With Adverse Events at Primary Analysis

Intervention	percentage of participants (Number)
Placebo+Fulvestrant	89.7
Taselisib+Fulvestrant	95.4

Percentage of Participants With Clinical Benefit, as Assessed According to RECIST v1.1 at Final Analysis

Clinical benefit was defined as objective response (PR+CR), or no disease progression lasting for more than or equal to (>/=) 24 weeks since randomization. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions). Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression. (NCT02340221)
Timeframe: From randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to approximately 6.2 years)

Intervention	percentage of participants (Number)
Placebo+Fulvestrant	45.5
Taselisib+Fulvestrant	59.5

Percentage of Participants With Clinical Benefit, as Assessed According to RECIST v1.1 at Primary Analysis

Intervention	percentage of participants (Number)
Placebo+Fulvestrant	37.3
Taselisib+Fulvestrant	51.5

Percentage of Participants With Objective Response (Partial Response [PR] Plus Complete Response [CR]), as Assessed Using RECIST v.1.1 at Primary Analysis

PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions). (NCT02340221)
Timeframe: From randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to the 15 Oct 2017 data cutoff, approximately 2.5 years)

Intervention	percentage of participants (Number)
Placebo+Fulvestrant	11.9
Taselisib+Fulvestrant	28.0

Percentage of Participants With Objective Response (PR Plus CR), as Assessed Using RECIST v.1.1 at Final Analysis

Intervention	percentage of participants (Number)
Placebo+Fulvestrant	13.4
Taselisib+Fulvestrant	31.1

PFS as Assessed by BICR Using RECIST v1.1 at Final Analysis

PFS was defined as the time from randomization to disease progression as determined by BICR with the use of RECIST v1.1 or death due to any cause, whichever occurred earlier. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression. (NCT02340221)
Timeframe: From randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to approximately 6.2 years)

Intervention	months (Median)
Placebo+Fulvestrant	5.55
Taselisib+Fulvestrant	9.20

PFS as Assessed by Blinded Independent Central Review (BICR) Using RECIST v1.1 at Primary Analysis

Intervention	months (Median)
Placebo+Fulvestrant	5.39
Taselisib+Fulvestrant	8.97

PFS as Assessed by Investigator Using RECIST v1.1 at Final Analysis

PFS was defined as the time from randomization to disease progression as determined by the investigator with the use of RECIST v1.1 or death due to any cause, whichever occurred earlier. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression. (NCT02340221)
Timeframe: From randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to approximately 6.2 years)

Intervention	months (Median)
Placebo+Fulvestrant	5.55
Taselisib+Fulvestrant	8.05

Progression-Free Survival (PFS) as Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) at Primary Analysis

PFS was defined as the time from randomization to disease progression as determined by the investigator with the use of RECIST v1.1 or death due to any cause, whichever occurred earlier. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression. (NCT02340221)
Timeframe: From randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier (up to the 15 Oct 2017 data cutoff, approximately 2.5 years)

Intervention	months (Median)
Placebo+Fulvestrant	5.39
Taselisib+Fulvestrant	7.43

Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Score

"The EORTC QLQ-C30 consists of 30 questions that comprise aspects of participant's functioning assessment (physical, emotional, role, cognitive, and social); symptom scales (fatigue; nausea, vomiting, and pain; the global health/quality of life [QoL]); and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhoea, and financial difficulties), within a recall period of the past week. Most questions used a 4-point scale (1=Not at all to 4=Very much; two questions used a 7-point scale (1=Very poor to 7=Excellent). Scores were averaged and transformed to a 0-100 scale; a higher score for Global Qol/functional scales=better level of functioning; a higher score for symptom scale=greater degree of symptoms." (NCT02340221)
Timeframe: Baseline, C2D1 up to C7D1 (each cycle=28 days)

Intervention	score on a scale (Mean)
	Appetite Loss: Baseline	Appetite Loss: Change at C2D1	Appetite Loss: Change at C3D1	Appetite Loss: Change at C4D1	Appetite Loss: Change at C5D1	Appetite Loss: Change at C6D1	Appetite Loss: Change at C7D1	Cognitive Functioning: Baseline	Cognitive Functioning: Change at C2D1	Cognitive Functioning: Change at C3D1	Cognitive Functioning: Change at C4D1	Cognitive Functioning: Change at C5D1	Cognitive Functioning: Change at C6D1	Cognitive Functioning: Change at C7D1	Constipation: Baseline	Constipation: Change at C2D1	Constipation: Change at C3D1	Constipation: Change at C4D1	Constipation: Change at C5D1	Constipation: Change at C6D1	Constipation: Change at C7D1	Diarrhoea: Baseline	Diarrhoea: Change at C2D1	Diarrhoea: Change at C3D1	Diarrhoea: Change at C4D1	Diarrhoea: Change at C5D1	Diarrhoea: Change at C6D1	Diarrhoea: Change at C7D1	Dyspnoea: Baseline	Dyspnoea: Change at C2D1	Dyspnoea: Change at C3D1	Dyspnoea: Change at C4D1	Dyspnoea: Change at C5D1	Dyspnoea: Change at C6D1	Dyspnoea: Change at C7D1	Emotional Functioning: Baseline	Emotional Functioning: Change at C2D1	Emotional Functioning: Change at C3D1	Emotional Functioning: Change at C4D1	Emotional Functioning: Change at C5D1	Emotional Functioning: Change at C6D1	Emotional Functioning: Change at C7D1	Fatigue: Baseline	Fatigue: Change at C2D1	Fatigue: Change at C3D1	Fatigue: Change at C4D1	Fatigue: Change at C5D1	Fatigue: Change at C6D1	Fatigue: Change at C7D1	Financial Difficulties: Baseline	Financial Difficulties: Change at C2D1	Financial Difficulties: Change at C3D1	Financial Difficulties: Change at C4D1	Financial Difficulties: Change at C5D1	Financial Difficulties: Change at C6D1	Financial Difficulties: Change at C7D1	Global Health Status/ QoL: Baseline	Global Health Status/ QoL: Change at C2D1	Global Health Status/ QoL: Change at C3D1	Global Health Status/ QoL: Change at C4D1	Global Health Status/ QoL: Change at C5D1	Global Health Status/ QoL: Change at C6D1	Global Health Status/ QoL: Change at C7D1	Insomnia: Baseline	Insomnia: Change at C2D1	Insomnia: Change at C3D1	Insomnia: Change at C4D1	Insomnia: Change at C5D1	Insomnia: Change at C6D1	Insomnia: Change at C7D1	Nausea/Vomiting: Baseline	Nausea/Vomiting: Change at C2D1	Nausea/Vomiting: Change at C3D1	Nausea/Vomiting: Change at C4D1	Nausea/Vomiting: Change at C5D1	Nausea/Vomiting: Change at C6D1	Nausea/Vomiting: Change at C7D1	Pain: Baseline	Pain: Change at C2D1	Pain: Change at C3D1	Pain: Change at C4D1	Pain: Change at C5D1	Pain: Change at C6D1	Pain: Change at C7D1	Physical Functioning: Baseline	Physical Functioning: Change at C2D1	Physical Functioning: Change at C3D1	Physical Functioning: Change at C4D1	Physical Functioning: Change at C5D1	Physical Functioning: Change at C6D1	Physical Functioning: Change at C7D1	Role Functioning: Baseline	Role Functioning: Change at C2D1	Role Functioning: Change at C3D1	Role Functioning: Change at C4D1	Role Functioning: Change at C5D1	Role Functioning: Change at C6D1	Role Functioning: Change at C7D1	Social Functioning: Baseline	Social Functioning: Change at C2D1	Social Functioning: Change at C3D1	Social Functioning: Change at C4D1	Social Functioning: Change at C5D1	Social Functioning: Change at C6D1	Social Functioning: Change at C7D1
Placebo+Fulvestrant	15.9	-0.2	-4.3	-1.7	-0.4	-0.5	-5.7	85.3	0.7	0.9	1.8	-1.5	-0.5	-2.3	15.8	0.0	-2.3	-2.7	-1.3	-3.0	-4.6	6.3	-0.5	-0.9	-2.7	-2.6	-2.0	1.1	15.0	4.1	2.8	0.7	2.6	3.0	1.7	73.1	4.0	4.5	4.5	5.2	2.1	5.3	30.8	2.0	-1.5	-0.2	-0.1	3.3	1.0	18.5	-1.1	-0.9	0.7	-0.4	5.6	-0.6	65.2	-0.1	-1.0	-1.5	0.3	-1.6	-1.1	26.0	-0.9	-3.4	-4.0	-0.4	-2.0	-4.1	5.9	0.1	0.7	0.3	-1.1	1.5	2.6	28.0	-0.2	-3.7	-3.2	-3.3	-1.0	0.3	76.7	-1.1	2.0	1.5	2.0	0.9	1.6	79.1	-2.0	-0.4	0.3	1.8	-1.3	-0.3	83.2	-0.8	1.3	1.8	0.9	-0.8	0.6
Taselisib+Fulvestrant	15.3	6.2	8.7	8.4	6.0	6.6	4.6	85.9	-1.1	-2.9	-1.7	-3.2	-2.8	-0.8	14.5	-6.0	-4.9	-5.5	-4.0	-3.5	-6.9	5.0	10.2	13.7	13.1	11.1	14.0	15.6	15.4	-2.1	0.0	0.0	1.6	0.2	-2.1	71.9	5.1	2.3	2.6	-0.4	2.4	2.8	30.8	-0.5	1.8	2.4	2.8	2.4	1.8	19.2	-2.8	-1.6	-0.3	0.3	0.4	2.1	67.4	1.0	-1.5	-1.6	-2.8	-3.4	-1.0	26.5	-3.8	-4.1	-1.0	-3.9	-2.4	-1.8	6.7	1.6	2.2	2.3	0.5	-0.6	2.2	27.1	-5.0	-3.5	-1.7	-4.3	-2.2	-4.4	78.4	1.6	0.8	0.3	1.0	1.1	0.6	78.7	1.7	-1.0	0.4	-1.6	-1.6	0.0	81.2	2.7	-0.8	-0.5	-1.0	-1.6	0.1

Change From Baseline in Modified EORTC Quality of Life Questionnaire Breast Cancer Module 23 (QLQ-BR23) Score

EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of functional scales (body image, sexual enjoyment, sexual functioning, future perspective [FP]) and symptom scales (systemic side effects [SE], upset by hair loss, arm symptoms, breast symptoms). Questions used a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores were averaged and transformed to a 0-100 scale. Higher scores for the functional scales indicated a higher/better level of functioning/healthy functioning. Higher scores for the symptom scales indicated worse symptoms. (NCT02340221)
Timeframe: Baseline, C2D1 up to C7D1 (each cycle=28 days)

Intervention	score on a scale (Mean)
	Arm Symptoms: Baseline	Arm Symptoms: Change at C2D1	Arm Symptoms: Change at C3D1	Arm Symptoms: Change at C4D1	Arm Symptoms: Change at C5D1	Arm Symptoms: Change at C6D1	Arm Symptoms: Change at C7D1	Body Image: Baseline	Body Image: Change at C2D1	Body Image: Change at C3D1	Body Image: Change at C4D1	Body Image: Change at C5D1	Body Image: Change at C6D1	Body Image: Change at C7D1	Breast Symptoms: Baseline	Breast Symptoms: Change at C2D1	Breast Symptoms: Change at C3D1	Breast Symptoms: Change at C4D1	Breast Symptoms: Change at C5D1	Breast Symptoms: Change at C6D1	Breast Symptoms: Change at C7D1	Future Perspective: Baseline	Future Perspective: Change at C2D1	Future Perspective: Change at C3D1	Future Perspective: Change at C4D1	Future Perspective: Change at C5D1	Future Perspective: Change at C6D1	Future Perspective: Change at C7D1	Sexual Enjoyment: Baseline	Sexual Enjoyment: Change at C2D1	Sexual Enjoyment: Change at C3D1	Sexual Enjoyment: Change at C4D1	Sexual Enjoyment: Change at C5D1	Sexual Enjoyment: Change at C6D1	Sexual Enjoyment: Change at C7D1	Sexual Functioning: Baseline	Sexual Functioning: Change at C2D1	Sexual Functioning: Change at C3D1	Sexual Functioning: Change at C4D1	Sexual Functioning: Change at C5D1	Sexual Functioning: Change at C6D1	Sexual Functioning: Change at C7D1	Systematic Therapy SEs: Baseline	Systematic Therapy SEs: Change at C2D1	Systematic Therapy SEs: Change at C3D1	Systematic Therapy SEs: Change at C4D1	Systematic Therapy SEs: Change at C5D1	Systematic Therapy SEs: Change at C6D1	Systematic Therapy SEs: Change at C7D1	Upset by Hair Loss: Baseline	Upset by Hair Loss: Change at C2D1	Upset by Hair Loss: Change at C3D1	Upset by Hair Loss: Change at C4D1	Upset by Hair Loss: Change at C5D1	Upset by Hair Loss: Change at C6D1	Upset by Hair Loss: Change at C7D1
Placebo+Fulvestrant	15.5	0.1	-0.7	-1.4	0.8	1.1	-1.2	82.0	1.8	1.6	1.1	0.2	1.1	5.6	8.7	0.0	-0.8	0.1	-0.9	1.7	0.3	47.4	3.4	5.1	6.0	6.0	6.9	12.9	51.9	5.9	4.8	-8.3	-4.8	-6.7	-13.3	89.6	1.6	1.4	1.9	-0.8	2.4	2.7	15.7	0.2	1.2	1.5	2.4	2.9	3.5	23.2	-11.9	-7.7	2.6	0.0	11.1	4.2
Taselisib+Fulvestrant	19.3	-5.4	-6.1	-5.8	-6.6	-5.0	-6.0	80.8	1.5	1.1	1.8	0.0	0.4	-0.3	11.0	-3.0	-3.5	-3.0	-2.0	-2.0	-3.2	47.3	6.8	4.3	7.0	5.0	9.0	7.0	62.8	0.0	1.3	4.2	2.6	-5.9	9.5	89.9	1.5	1.8	1.6	2.6	2.7	2.3	14.7	2.5	4.0	4.0	5.5	5.7	4.8	27.0	-4.3	0.0	0.0	10.7	16.7	14.1

Maximum Observed Plasma Concentration (Cmax) of Taselisib

(NCT02340221)
Timeframe: 1 to 4 hours (hrs) post-dose on Cycle (C) 1, Day (D) 1; 0 to 3 hrs pre-dose and 2 to 6 hrs post dose on Cycle 2, Day 1 (each cycle=28 days)

Intervention	ng/mL (Mean)
	C1D1	C2D1
Taselisib+Fulvestrant	18.2	66.6

Minimum Observed Plasma Concentration (Cmin) of Taselisib

(NCT02340221)
Timeframe: 1 to 4 hrs post-dose on Cycle 1, Day 1; 0 to 3 hrs pre-dose and 2 to 6 hrs post dose on Cycle 2, Day 1; 0 to 3 hrs pre-dose on Cycle 6, Day 1 (each cycle=28 days)

Intervention	ng/mL (Mean)
	C2D1	C6D1
Taselisib+Fulvestrant	42.8	35.3

Kaplan Meier Estimate of Duration of Response (DoR)

Duration of response was defined as the time from the first tumor assessment when the confirmed CR/PR criterion was first met to the date of disease progression, based on investigator's assessment following RECIST Version 1.1 criteria. (NCT02374099)
Timeframe: From the date of randomization of study drug to the data cut-off of 13 December 2016; follow up for duration of response was 21 months

Intervention	months (Median)
CC-486 and Fulvestrant	NA
Fulvestrant	NA

Kaplan Meier Estimate of Overall Survival

Overall survival was defined as the time from the date of randomization to the date of death (from any cause). All participants who were lost to follow up prior to the end of the study or who were withdrawn from the study were censored at the time of last contact. (NCT02374099)
Timeframe: From the date of randomization of study drug to the data cut off date of 13 December 2016; participants were followed for overall survival for 21 months

Intervention	months (Median)
CC-486 and Fulvestrant	NA
Fulvestrant	NA

Kaplan-Meier Estimate of Progression Free Survival (PFS)

Progression-free survival was defined as the duration from the date of randomization to the date of disease progression (DP) based on investigator's assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 or death (from any cause), whichever occurred first. Per RECIST 1.1, progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions from nadir or appearance of a new lesion. (NCT02374099)
Timeframe: From the date of randomization of study drug to the date of the cut off date of 13 December 2016; follow-up for PFS was 21 months

Intervention	months (Median)
CC-486 and Fulvestrant	5.49
Fulvestrant	5.46

Percentage of Participants Who Achieved a Confirmed Complete Response (CR) or Partial Response (PR) to Treatment (Objective Response Rate) Based On the Investigator Assessment

Overall response rate was defined as the percentage of participants who achieved a confirmed complete response or partial response based on RECIST Version 1.1 criteria. RECIST criteria v 1.1 defined a CR as the disappearance of all target lesions and a PR with at least a 30% decrease in the sum of diameters of target lesions from baseline. The two-sided 95% exact binomial CI for each arm was estimated by the Clopper-Pearson method. (NCT02374099)
Timeframe: Disease response was assessed every 8 weeks, for the first 24 weeks, then every 12 weeks until DP; from date of randomization of study drug to data cut-off date of 13 December 2016; follow-up for overall response was 21 months

Intervention	Percentage of Participants (Number)
CC-486 and Fulvestrant	8.3
Fulvestrant	2.0

Percentage of Participants Who Achieved a Confirmed CR, PR or Stable Disease (SD) for ≥ 24 Weeks (Clinical Benefit Rate) by Investigator Assessment

Percentage of participants with CR or PR or SD was defined per RECIST criteria v 1.1 as a CR that includes a disappearance of all target lesions, a PR was defined as having at least a 30% decrease in the sum of diameters of target lesions from baseline and SD as neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for progressive disease. The two-sided 95% exact binomial CI each arm was estimated by the Clopper-Pearson method. (NCT02374099)
Timeframe: Disease response was assessed every 8 weeks, for the first 24 weeks, then every 12 weeks until DP; from date of randomization of study drug to the data cut-off date of 13 December 2016; follow-up for clinical benefit response was 21 months

Intervention	Percentage of Participants (Number)
CC-486 and Fulvestrant	31.3
Fulvestrant	30.6

Number of Participants With Treatment Emergent Adverse Events (TEAEs)

Treatment-emergent adverse events (TEAEs) were defined as any AEs that begin or worsen with an onset date on or after the date of the first dose of IP through 28 days after the last dose. A serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs were graded based on the participant's symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); AEs were evaluated for severity as follows: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death. (NCT02374099)
Timeframe: Randomization to 28 days after the last dose of IP; those AEs known at any time thereafter being related to IP; up to the last subject last visit of 21 November 2017; TEAE follow-up occurred up to 155 weeks and 2 days

Intervention	Participants (Count of Participants)
	TEAE	Grade 3 or 4 TEAE	Grade 5 TEAE (Death)	Serious TEAE	TEAE Leading to Stopping of Any IP	TEAE Leading to Dose Reduction of any IP	TEAE Leading to Dose Interruption of any IP	Treatment Related TEAE	Treatment Related TEAE Grade 3 or 4 TEAE	Treatment Related TEAE Grade 5 Death	Treatment Related Serious TEAE
CC-486 and Fulvestrant	46	32	2	10	14	19	22	46	29	0	4
Fulvestrant	45	15	1	7	1	0	3	31	2	0	0

Objective Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR)

ORR is defined as the number of participants who achieve a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the total number of participants randomized to the corresponding treatment arm [intent-to-treat (ITT) population], based on investigator-assessed tumor responses.CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking in reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. Confirmations of CR and PR are not required. (NCT04031885)
Timeframe: Randomization to Measured Progressive Disease (Up to 12 Months)

Intervention	percentage of participants (Number)
Abemaciclib + Fulvestrant	0
Standard Chemotherapy	0

Number of Participants With Dose Limiting Toxicities (DLT) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)

Number of participants with DLT in the first cycle for the determination of the MTD. (NCT03238196)
Timeframe: From the time of randomization up to 4 weeks of treatment (cycle 1), for each patient

Intervention	participants (Number)
Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 5mg (Escalation)	0
Fulvestrant 500mg/Palbociclib 125mg/Erdafitinib 6mg (Escalation)	0
Fulvestrant 500mg, Palbociclib 125mg and Erdafitinib 8mg (Escalation)	2

Change From Baseline of Plasma Estradiol Levels

"Plasma estradiol levels are obtained and measured from blood samples collected from each participant.~Difference in change from baseline to 9 weeks in plasma estradiol levels" (NCT02911844)
Timeframe: Baseline to 9 weeks

Intervention	pg/ml (Median)
Fulvestrant	-1.26

Change From Baseline of Plasma NT-proBNP Level

"Plasma NT-proBNP levels are obtained and measured from blood samples collected from each participant.~Difference in change from baseline to 9 weeks in plasma NT-proBNP levels" (NCT02911844)
Timeframe: Baseline to 9 weeks

Intervention	pg/ml (Median)
Fulvestrant	42.1

Change From Baseline of Six Minute Walk Distance

Measure obtained from six minute walk test completed by participants Difference in change from baseline to 9 weeks in the six minute walk test distance (NCT02911844)
Timeframe: Baseline to 9 weeks

Intervention	meters (Median)
Fulvestrant	31

Change From Baseline of Tricuspid Annular Plane Systolic Excursion (TAPSE)

Measure obtained from echocardiogram completed on participants Difference in change from baseline to 9 weeks in TAPSE (NCT02911844)
Timeframe: Baseline to 9 weeks

Intervention	millimeter (Median)
Fulvestrant	2

Clinical Benefit Rate

Clinical benefit rate was defined as the percentage of participants experiencing stable disease (SD) of at least 24 weeks plus complete response (CR) and partial response (PR). Response was evaluated via changes from baseline in radiological tumor measurements performed after every two treatment cycles and at the end of treatment or time of progression. Response was evaluated using RECIST version 1.0 guidelines, where CR is the disappearance of all target lesions; PR is >=30% decrease in the sum of the longest diameter(LD) of target lesions; SD is neither sufficient shrinkage in sum of longest diameter of target lesions to be PR nor increase of >=20%. (NCT00534417)
Timeframe: Response to treatment was assessed after every 8 weeks of treatment

Intervention	percentage of participants (Number)
Capecitabine and Fulvestrant	58.5

Overall Response Rate

Overall response rate was defined as the percentage of participants experiencing complete response (CR) and partial response (PR). Response was evaluated via changes from baseline in radiological tumor measurements performed after every two treatment cycles and at the end of treatment or time of progression. Response was evaluated using RECIST version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter (LD) of target lesions; Stable Disease (SD) is neither sufficient shrinkage in sum of LD of target lesions to be PR nor increase of >=20%; Progressive Disease (PD) is the increase in existing lesions or new lesions. (NCT00534417)
Timeframe: Response to treatment was assessed after every 8 weeks of treatment

Intervention	percentage of participants (Number)
Capecitabine and Fulvestrant	24.4

Overall Survival (OS)

Overall survival is defined as the time from treatment start until death from any cause. The median overall survival time is used to measure OS. (NCT00534417)
Timeframe: OS was measured from day 1 of treatment until time of death from any cause, up to 32.5 months.

Intervention	Months (Median)
Capecitabine and Fulvestrant	28.65

Progression-free Survival (PFS)

Disease progression was determined through radiology imaging measurements and by clinical or symptomatic progression during or after treatment. Progression is defined per RECIST v1.0 guidelines as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions. (NCT00534417)
Timeframe: PFS was measured from day 1 of treatment until time of progression (assessed every 8 weeks) or death, whichever came first, up to 32.5 months.

Intervention	Months (Median)
Capecitabine and Fulvestrant	14.98

Time to Progression (TTP)

Time to progression is defined as the time from treatment start until objective tumor progression. Progression is defined per Response Evaluation Criteria in Solid Tumors (RECIST)v1.0 guidelines as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions. The median time to progression is the parameter used to describe TTP. (NCT00534417)
Timeframe: TTP was measured from day 1 of treatment until time of progression (assessed every 8 weeks), up to 29 months.

Intervention	Months (Median)
Capecitabine and Fulvestrant	26.94

Best Overall Response

Best overall response is defined as the best response across all time points. Response was evaluated via changes from baseline in radiological tumor measurements performed after every two treatment cycles and at the end of treatment or time of progression. Response was evaluated using RECIST version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter (LD) of target lesions; Stable Disease (SD) is neither sufficient shrinkage in sum of LD of target lesions to be PR nor increase of >=20%; Progressive Disease (PD) is the increase in existing lesions or new lesions. (NCT00534417)
Timeframe: Response to treatment was assessed after every 8 weeks of treatment

Intervention	participants (Number)
	Complete response (CR)	Partial response (PR)	Stable disease (SD)	Progressive disease (PD)
Capecitabine and Fulvestrant	2	8	28	3

Patients Experiencing Severe Symptom Burden (Physical Functioning)

The subject rates each question about physical functioning on a scale of 0 through 10, where 0 is not bad and 10 is as bad as possible. Severe symptoms are indicated by a response > or = to 7 on an item. (NCT00534417)
Timeframe: The questionnaire was administered on day 1 of every cycle (approximately every 4 weeks) during study treatment.

Intervention	percentage of participants (Number)
	Attend paid job (N=27)	Attend social activity	Bathe or dress self	Cook for self	Driving (N=27)	Function normally	Hard work or activity (N=27)	Household work	Light work or activity	Run (N=27)	Run errands	Sit up	Stay out of bed	Walk
Capecitabine and Fulvestrant	37.0	7.1	10.7	10.7	25.9	14.3	33.3	21.4	10.7	33.3	17.9	10.7	7.1	17.9

Patients Experiencing Severe Symptom Burden (Physical Symptoms)

The subject rates each question about physical symptoms on a scale of 0 through 10, where 0 is not bad and 10 is as bad as possible. Severe symptoms are indicated by a response > or = to 7 on an item. (NCT00534417)
Timeframe: The questionnaire was administered on day 1 of every cycle (approximately every 4 weeks) during study treatment.

Intervention	percentage of participants (Number)
	Hives/Welts	Sinus problems	Swelling	Fatigue	Weight loss	Change in taste	Difficulty hearing	Reduced sexual enjoyment, interest, or performance	Dry eyes	Tearing	Trouble seeing	Constipation	Decrease in appetite	Diarrhea	Heartburn	Increase in appetite	Problem with urination	Vaginal dryness	Bruising	New lump/mass	Breast tenderness	Dry skin	Hair loss	Itching	Nails change	Joint pain	Muscle aches	Weakness of body parts	Burning sensation in hands or feet	Daytime sleepiness	Dizziness/lightheadedness	Memory loss	Numbness/tingling	Trouble thinking	Headache	Pain	Coughing	Shortness of breath	Wheezing
Capecitabine and Fulvestrant	3.3	3.3	10.0	26.7	10.0	6.7	3.3	10.0	10.0	10.0	16.7	20.0	6.7	3.3	6.7	3.3	3.3	3.3	3.3	6.7	3.3	13.3	3.3	13.3	10.0	26.7	26.7	10.0	10.0	10.0	3.3	6.7	13.3	10.0	6.7	26.7	13.3	6.7	6.7

Patients Experiencing Severe Symptom Burden (Psychiatric Symptoms)

The subject rates each question about psychiatric symptoms on a scale of 0 through 10, where 0 is not bad and 10 is as bad as possible. Severe symptoms are indicated by a response > or = to 7 on an item. (NCT00534417)
Timeframe: The questionnaire was administered on day 1 of every cycle (approximately every 4 weeks) during study treatment.

Intervention	percentage of participants (Number)
	Crying/feeling like crying	Feeling helpless	Feeling hopeless	Feeling I would be better off dead	Lost interest in people	Lost interest in pleasurable activities	Nervous, tense, anxious	Sad/depressed	Worry
Capecitabine and Fulvestrant	10.3	6.9	10.3	3.4	3.4	10.3	13.8	10.3	10.3

Part I Only: Clinical Benefit Rate (CR+PR+SD≥6months) of Patients Who Received Neratinib Alone

"Imaging for clinical benefit rate occurred at baseline (for an initial comparison scan) and every 2 cycles (28 day length) thereafter.~Complete response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level.~Partial response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.~Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. Must have had stable disease for at least 6 months." (NCT01670877)
Timeframe: Through completion of treatment (median treatment time of 90 days, full range 54-716 days)

Intervention	Participants (Count of Participants)
Part I: Neratinib Only	5

Part II ER-cohort Only: Clinical Benefit Rate (CR+PR+SD≥6months) of Neratinib in Patients With Metastatic HER2-, ER- Breast Cancer That Carry HER2 Mutation

Intervention	Participants (Count of Participants)
Part II: Neratinib Only (ER-)	1

Part II ER-cohort Only: Progression-free Survival (PFS)

"Progression-free survival is defined as the number of weeks from start of treatment until disease progression or death.~Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase." (NCT01670877)
Timeframe: Through completion of treatment (median treatment time of 62 days, full range 56-413 days)

Intervention	weeks (Median)
Part II: Neratinib Only (ER-)	8.5

Part II Fulvestrant-naive ER+ Cohort Only: Clinical Benefit (CR+PR+SD≥6 Months) of Neratinib + Fulvestrant in Patients With Metastatic HER2- ER+ Fulvestrant-naive Breast Cancer That Carry HER2 Mutation

Intervention	Participants (Count of Participants)
Part II: Neratinib + Fulvestrant (ER+, Fulvestrant-naive)	3

Part II Fulvestrant-naive ER+ Cohort Only: Progression-free Survival (PFS)

Intervention	weeks (Median)
Part II: Neratinib + Fulvestrant (ER+, Fulvestrant-naive)	20

Part II Fulvestrant-naive ER+ Cohort Only: Response Rate (RR)

"RR is defined as number of participants with complete response or partial response as best response.~Complete response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level.~Partial response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters." (NCT01670877)
Timeframe: Through completion of treatment (median treatment time of 140.5 days, full range 48-770 days)

Intervention	Participants (Count of Participants)
Part II: Neratinib + Fulvestrant (ER+, Fulvestrant-naive)	3

Part II Fulvestrant-treated ER+ Cohort Only: Clinical Benefit Rate (CR+PR+SD≥6months) of Neratinib + Fulvestrant in Patients With Metastatic HER2- ER+ Fulvestrant-treated Breast Cancer That Carry HER2 Mutation

Intervention	Participants (Count of Participants)
Part II: Neratinib + Fulvestrant (ER+. Prior Fulvestrant-tx)	8

Part II Fulvestrant-treated ER+ Cohort Only: Progression-free Survival (PFS)

Intervention	weeks (Median)
Part II: Neratinib + Fulvestrant (ER+. Prior Fulvestrant-tx)	24

Part II Fulvestrant-treated ER+ Cohort Only: Response Rate (RR)

Intervention	Participants (Count of Participants)
Part II: Neratinib + Fulvestrant (ER+. Prior Fulvestrant-tx)	5

Correlate the Presence of HER2 Mutation Subtype With Progression-free Survival

"Progression-free survival is defined as the number of weeks from start of treatment until disease progression or death.~Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase." (NCT01670877)
Timeframe: Through completion of follow-up; follow-up was through 30 days following completion of treatment (median follow-up of 142 days, full range 54-800 days)

,,,

Intervention	weeks (Median)
	ECD mutation	Exon 20 ins mutation	KD mutation
Part I: Neratinib Only	11.0000	26.0000	9.0000
Part II: Neratinib + Fulvestrant (ER+, Fulvestrant-naive)	48.5000	26.000	8.0000
Part II: Neratinib + Fulvestrant (ER+. Prior Fulvestrant-tx)	3.0000	36.5000	16.0000
Part II: Neratinib Only (ER-)	8.0000	17.0000	6.5000

Correlate the Presence of HER2 Mutation Subtype With Tumor Staging at Initial Diagnosis

"Staging occurred at initial diagnosis after physical exam, mammogram, and other diagnostic imaging tests. The staging also takes into account pathology reports from the breast biopsy or surgery.~Stage I has a better outcome than Stage IV." (NCT01670877)
Timeframe: At time of enrollment

,,,

Intervention	Participants (Count of Participants)
	ECD mutation : Stage I	ECD mutation : Stage II	ECD mutation : Stage III	ECD mutation : Stage IV	ECD mutation : Unknown	Exon 20 ins mutation : Stage I	Exon 20 ins mutation : Stage II	Exon 20 ins mutation : Stage III	Exon 20 ins mutation : Stage IV	Exon 20 ins mutation : Unknown	KD mutation : Stage I	KD mutation : Stage II	KD mutation : Stage III	KD mutation : Stage IV	KD mutation : Unknown
Part I: Neratinib Only	0	3	0	0	0	0	3	1	0	0	2	2	3	1	1
Part II: Neratinib + Fulvestrant (ER+, Fulvestrant-naive)	0	1	0	0	1	0	1	0	0	0	2	2	0	2	2
Part II: Neratinib + Fulvestrant (ER+. Prior Fulvestrant-tx)	1	2	0	0	0	0	1	2	0	1	3	6	6	1	1
Part II: Neratinib Only (ER-)	0	1	0	1	0	0	0	1	0	0	1	1	0	0	0

Number of Participants With HER2 Mutation Subtype and Histology Subtype

(NCT01670877)
Timeframe: At the time of enrollment

,,,

Intervention	Participants (Count of Participants)
	ECD mutation : Ductal histology	ECD mutation : Other histology	Exon 20 ins mutation : Ductal histology	Exon 20 ins mutation : Other histology	KD mutation : Ductal histology	KD mutation : Other histology
Part I: Neratinib Only	3	0	2	2	5	4
Part II: Neratinib + Fulvestrant (ER+, Fulvestrant-naive)	1	1	1	0	5	3
Part II: Neratinib + Fulvestrant (ER+. Prior Fulvestrant-tx)	1	2	2	2	7	10
Part II: Neratinib Only (ER-)	1	1	0	1	1	1

Number of Participants With HER2 Mutation Subtype and Tumor Grade

"-Cancer cells are graded when they are removed from the breast. The grade is based on how much the cancer cells look like normal cells.~A low grade number (grade 1) usually means the cancer is slower-growing and less likely to spread.~An intermediate grade number (grade 2) means the cancer is growing faster than a grade 1 cancer but slower than a grade 3 cancer.~A high grade number (grade 3) means a faster-growing cancer that's more likely to spread." (NCT01670877)
Timeframe: A time of enrollment

,,,

Intervention	Participants (Count of Participants)
	ECD mutation : Tumor grade I/II	ECD mutation : Tumor grade III	ECD mutation : Unknown	Exon 20 ins mutation : Tumor grade I/II	Exon 20 ins mutation : Tumor grade III	Exon 20 ins mutation : Unknown	KD mutation : Tumor grade I/II	KD mutation : Tumor grade III	KD mutation : Unknown
Part I: Neratinib Only	2	1	0	1	3	0	6	3	0
Part II: Neratinib + Fulvestrant (ER+, Fulvestrant-naive)	1	0	1	0	1	0	4	1	3
Part II: Neratinib + Fulvestrant (ER+. Prior Fulvestrant-tx)	2	0	1	2	0	2	11	3	3
Part II: Neratinib Only (ER-)	0	3	0	1	0	0	0	2	0

Progression-free Survival (PFS) of Patients Treated With Neratinib Alone in Patients With Metastatic HER2- But HER2 Mutated Breast Cancer by ER Status and by HER2 Mutations (Activating Versus Unknown Significance)

"Participants were followed for progressive disease from start of treatment until completion of follow-up.~Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase." (NCT01670877)
Timeframe: Through completion of follow-up; follow-up was through 30 days following completion of treatment (median follow-up of 92 days, full range 86 days-443 days)

Intervention	weeks (Number)
	Activating mutation - L7L755S	Activating mutation - S310F	Activating mutation - A775_G776insYVMA
Part II: Neratinib Only (ER-)	9	8	17

Safety and Tolerability of Neratinib in Combination With Fulvestrant in Patients With HER2- ER+ HER2 Mutated Breast Cancer as Measured by Number of Participants With Related Adverse Events

-CTCAE v 4.0 will be used to record adverse events. Related includes those possibly, probably, or definitely related to the treatment regimen. (NCT01670877)
Timeframe: Through completion of follow-up; follow-up was through 28 days following completion of treatment (median follow-up of 140 days, full range 52-798 days)

,,,,,

Intervention	Participants (Count of Participants)
	Anemia	LVEF Decrease	Heart failure with preserved ejection fraction	Tinnitus	Dry eye	Abdominal cramping	Abdominal pain	Bloating	Constipation	Diarrhea	Dry mouth	Dyspepsia	Flatulence	Mucositis oral	Nausea	Stomach pain	Stomatitis	Vomiting	Fatigue	Fever	Generalized weakness	Pain	Rhinitis infective	Upper respiratory infection	Urinary tract infection	Alaline aminotransferase increased	Alkaline phosphatase increased	Alkaline phosphatase decreased	Aspartate aminotransferase increased	CD4 lymphocytes decreased	Creatinine increased	Ejection fraction decreased	INR increased	Lymphocyte count decreased	Neutrophil count decreased	Platelet count decreased	Weight loss	White blood cell decreased	Anorexia	Dehydration	Hypercalcemia	Hyperglycemia	Hyperkalemia	Hypoalbuminemia	Hypocalcemia	Hypokalemia	Hyponatremia	Hypophosphatemia	Arthralgia	Back pain	Bone pain	Flank pain	Generalized muscle weakness	Joint range of motion decreased	Leg cramp	Muscle weakness left sided	Muscle weakness lower limb	Myalgia	Pain at injection site	Pain in extremity	Dizziness	Dysgeusia	Headache	Peripheral sensory neuropathy	Syncope	Depression	Insomnia	Acute kidney injury	Urinary tract obstruction	Urine discoloration	Urine odor	Cough	Dyspnea	Epistaxis	Hoarseness	Postnasal drip	Rhinorrhea	Alopecia	Dry hair	Dry skin	Nail changes	Pruritus	Rash acneiform	Rash maculopapular	Skin hyperpigmentation	Sterile abscess at subcutaneous injection site	Hot flashes	Hypotension
Crossover: Neratinib + Fulvestrant + Trastuzumab	1	0	1	0	0	0	0	0	0	1	0	0	0	0	1	0	0	2	1	0	0	0	0	0	0	1	0	0	1	0	1	0	0	0	1	1	1	0	2	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Crossover: Neratinib + Trastuzumab	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Part I: Neratinib Only	2	0	0	1	1	1	0	0	5	15	0	2	0	3	9	1	0	6	6	0	1	0	0	0	1	3	1	0	2	1	3	0	0	0	0	0	3	0	7	3	0	1	0	2	1	1	0	2	1	2	1	1	0	0	1	0	0	0	0	0	1	0	1	0	1	0	0	0	0	0	0	1	0	0	0	0	0	1	1	0	1	1	0	1	1	0	1	1
Part II: Neratinib + Fulvestrant (ER+, Fulvestrant-naive)	1	0	0	0	0	0	2	0	1	8	0	1	0	0	4	0	0	0	5	0	0	0	0	0	2	2	1	0	3	0	0	0	1	2	0	0	0	0	7	1	0	0	0	0	0	1	1	0	0	0	0	0	0	1	0	0	0	0	1	1	2	1	2	0	1	1	1	1	1	1	1	0	0	1	0	1	0	0	0	0	0	0	2	1	0	1	1	1
Part II: Neratinib + Fulvestrant (ER+. Prior Fulvestrant-tx)	4	0	0	0	1	0	3	2	2	20	4	6	1	2	11	0	1	6	12	1	0	1	1	1	1	4	3	1	7	0	1	0	0	2	2	0	4	4	9	6	2	2	1	1	2	1	1	1	2	0	0	0	2	0	0	1	1	1	0	0	4	3	0	1	0	0	0	0	0	1	0	1	1	0	1	0	1	0	0	2	1	1	4	1	1	0	1	1
Part II: Neratinib Only (ER-)	0	0	0	0	0	0	0	1	0	5	0	0	0	0	3	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0

Apparent Total Body Clearance (CL/F) of AZD2014

The mean CL/F of AZD2014 in plasma following administration of [14C]-AZD2014 on Day 1 is presented. (NCT02640755)
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.

Intervention	L/h (Geometric Mean)
[14C]-AZD2014 (Period 1 [Day 1 - 8])	7.282

Apparent Volume of Distribution at Steady State (Vss/F) for AZD2014 in Plasma

The mean Vss/F of AZD2014 in plasma following administration of [14C]-AZD2014 on Day 1 is presented. (NCT02640755)
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.

Intervention	L (Geometric Mean)
[14C]-AZD2014 (Period 1 [Day 1 - 8])	37.86

Area Under the Plasma Concentration-time Curve (AUC) for AZD2014

Mean AUC for AZD2014 following administration of [14C]-AZD2014 on Day 1 is presented. (NCT02640755)
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.

Intervention	h*ng/mL (Geometric Mean)
[14C]-AZD2014 (Period 1 [Day 1 - 8])	17170

Best Percentage Change in Tumour Size From Baseline

Assessment of anti-tumour activity through measurement of tumour lesions. Tumour size was defined as the sum of the lengths of the longest diameters of the RECIST 1.1 target lesions. (NCT02640755)
Timeframe: RECIST 1.1 assessments were performed pre-dose at screening and then once every 8 weeks relative to the start of treatment in the Multiple Dose Period.

Intervention	Percentage change in tumour size (Median)
[14C]-AZD2014 Then AZD2014 Monotherapy	-8.75
[14C]-AZD2014 Then AZD2014 + Fulvestrant	3.1

Cumulative Percentage of [14C]-AZD2014 Recovered by Day 8

"The mean cumulative percentage of [14C]-AZD2014 dose recovered as total radioactivity by the end of the Single Dose Period (Day 1 - 8) is presented. The total [14C] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose.~Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection." (NCT02640755)
Timeframe: From pre-dose Day 1 to Day 8 of the Single Dose Period.

Intervention	Percentage of dose administered (Mean)
[14C]-AZD2014 (Period 1 [Day 1 - 8])	92.02

Half-life Associated With Terminal Slope (lambda_z) of a Semi-logarithmic Concentration-time Curve (t1/2[lambda_z]) for AZD2014 in Plasma

The mean t1/2(lambda_z) for AZD2014 in plasma following administration of [14C]-AZD2014 on Day 1 is presented. (NCT02640755)
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h ost [14C]-AZD2014 dose in the Single Dose Period.

Intervention	h (Geometric Mean)
[14C]-AZD2014 (Period 1 [Day 1 - 8])	3.571

Mean Residence Time (MRT) of AZD2014

The MRT of AZD2014 in plasma following administration of [14C]-AZD2014 on Day 1 is presented. (NCT02640755)
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.

Intervention	h (Geometric Mean)
[14C]-AZD2014 (Period 1 [Day 1 - 8])	5.200

Renal Clearance (CL[R]) of AZD2014 From Plasma.

CL(R) of AZD2014 from plasma up to 168 h post-dose. (NCT02640755)
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.

Intervention	L/h (Geometric Mean)
[14C]-AZD2014 (Period 1 [Day 1 - 8])	0.1596

Terminal Elimination Rate Constant (lambda_z) for AZD2014 in Plasma

The mean lambda_z of AZD2014 in plasma following administration of [14C]-AZD2014 on Day 1 is presented. (NCT02640755)
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.

Intervention	1/h (Geometric Mean)
[14C]-AZD2014 (Period 1 [Day 1 - 8])	0.1941

Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t]) for AZD2014 in Plasma and Saliva

Mean AUC(0-t) values in plasma and saliva for AZD2014 following administration of [14C]-AZD2014 on Day 1 are presented. (NCT02640755)
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.

Intervention	h*ng/mL (Geometric Mean)
	AUC(0-t) in plasma	AUC(0-t) in saliva
[14C]-AZD2014 (Period 1 [Day 1 - 8])	16510	6025

AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014

The mean concentrations of AZD2014 in plasma collected from each patient who received a single oral dose of 125 mg [14C]-AZD2014 are presented for time points of plasma sampling up to 24 hours post-dose. Geometric mean concentrations were not quantifiable after 24 hours. (NCT02640755)
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.

Intervention	ng/mL (Geometric Mean)
	0.5 h (n = 3)	1 h (n = 4)	1.5 h (n = 4)	2 h (n = 4)	3 h (n = 4)	4 h (n = 4)	6 h (n = 4)	8 h (n = 4)	12 h (n = 4)	24 h (n = 2)
[14C]-AZD2014 (Period 1 [Day 1 - 8])	3704	3090	2758	2409	1768	1439	917.7	619.4	314.6	35.11

AZD2014 Concentrations in Saliva Following Administration of [14C]-AZD2014

The mean concentrations of AZD2014 in saliva collected from each patient who received a single oral dose of 125 mg [14C]-AZD2014 are presented for time points of plasma sampling up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours. (NCT02640755)
Timeframe: Saliva was collected at 1, 2, 4, 6, 8, 10 and 12 h post [14C]-AZD2014 dose in the Single Dose Period.

Intervention	ng/mL (Geometric Mean)
	1 h (n = 3)	2 h (n = 4)	4 h (n = 4)	6 h (n = 4)	8 h (n = 4)	10 h (n = 3)	12 h (n = 2)
[14C]-AZD2014 (Period 1 [Day 1 - 8])	4159	416.3	169.1	75.08	73.27	32.59	33.96

Best Overall Response (BOR) Assessment

"Anti-tumour activity through assessment of BOR. BOR was defined for each patient as follows according to the RECIST 1.1 criteria:~Complete Response (CR): Disappearance of all target lesions since baseline. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions.~Stable Disease (SD): Any cases that do not qualify for either PR or progressive disease (PD).~PD: At least a 20% increase in the sum of the diameters of target lesions. BOR for each patient was determined as the best response recorded from the day study treatment started until progression or until the last evaluable RECIST tumour assessment in the absence of progression." (NCT02640755)
Timeframe: RECIST 1.1 assessments were performed pre-dose at screening and then once every 8 weeks relative to the start of treatment in the Multiple Dose Period.

Intervention	Participants (Number)
	Response: CR	Response: PR	Non-response: SD	Non-response: Progression	Non-response: Not evaluable
[14C]-AZD2014 Then AZD2014 + Fulvestrant	0	0	0	1	0
[14C]-AZD2014 Then AZD2014 Monotherapy	0	0	3	0	0

Cmax for Total [14C] Radioactivity in Whole Blood and Saliva

Mean [14C] radioactivity Cmax values in whole blood and saliva following administration of [14C]-AZD2014 on Day 1 are presented. (NCT02640755)
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.

Intervention	ngEq/mL (Geometric Mean)
	Cmax in whole blood	Cmax in saliva
[14C]-AZD2014 (Period 1 [Day 1 - 8])	3004	6966

Cumulative Percentage of Total [14C] Radioactivity Excreted in Stool as a Percentage of the Dose (fe Cum%[f])

"fe cum%(f) by the end of each collection period is presented following administration of [14C]-AZD2014.~Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection." (NCT02640755)
Timeframe: Stool was collected during the following periods: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 h post [14C]-AZD2014 dose in the Single Dose Period.

Intervention	Cumulative % of total [14C]-AZD2014 dose (Mean)
	0 - 24 h	0 - 48 h	0 - 72 h	0 - 96 h	0 - 120 h	0 - 144 h	0 - 168 h
[14C]-AZD2014 (Period 1 [Day 1 - 8])	18.23	52.85	77.04	78.59	79.25	79.70	79.94

Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R])

"fe cum%(R) by the end of each collection period is presented following administration of [14C]-AZD2014.~Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection." (NCT02640755)
Timeframe: Urine was collected during the following periods: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 h post [14C]-AZD2014 dose in the Single Dose Period.

Intervention	Cumulative % of total [14C]-AZD2014 dose (Mean)
	0 - 6 h	0 - 12 h	0 - 24 h	0 - 48 h	0 - 72 h	0 - 96 h	0 - 120 h	0 - 144 h	0 - 168 h
[14C]-AZD2014 (Period 1 [Day 1 - 8])	5.514	8.990	11.06	11.81	11.96	12.03	12.07	12.07	12.08

Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R])

Mean fe%(R) values per urine collection period are presented as a percentage of the total [14C]-AZD2014 dose administered on Day 1. (NCT02640755)
Timeframe: Urine was collected during the following periods: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 h post [14C]-AZD2014 dose in the Single Dose Period.

Intervention	% of total [14C]-AZD2014 dose (Mean)
	0 - 6 h	6 - 12 h	12 - 24 h	24 - 48 h	48 - 72 h	72 - 96 h	96 - 120 h	120 - 144 h	144 - 168 h
[14C]-AZD2014 (Period 1 [Day 1 - 8])	1.575	0.7471	0.3472	0.0460	0	0	0	NA	0

Maximum Observed Concentration (Cmax) of AZD2014 in Plasma and Saliva

Mean AZD2014 Cmax values in plasma and saliva following administration of [14C]-AZD2014 on Day 1 are presented. (NCT02640755)
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.

Intervention	ng/mL (Geometric Mean)
	Cmax in plasma	Cmax in saliva
[14C]-AZD2014 (Period 1 [Day 1 - 8])	4254	5410

Number of AEs Experienced by Patients.

AEs (including serious AEs [SAEs]) were collected from the time of informed consent (Visit 1) and throughout the study, including the 30-day follow-up. The numbers of patients experiencing any AEs and SAEs, causally related AEs and SAEs, and SAEs which were fatal are presented. (NCT02640755)
Timeframe: From Day 1 of the Single Dose Period to 30 days after the last dose of AZD2014 administered in the Multiple Dose Period.

Intervention	Participants (Number)
	Patients who experienced any AE	Patients who experienced any causally related AE	Patients who experienced any SAE	Patients who experienced any causally related SAE	Patients who experienced fatal SAE
[14C]-AZD2014 Then AZD2014 + Fulvestrant	1	1	1	0	0
[14C]-AZD2014 Then AZD2014 Monotherapy	3	3	1	0	0

Ratio of AZD2014 Concentration to Total Radioactivity Concentration in Saliva

The mean ratios of saliva AZD2014 to saliva radioactivity concentrations are presented for the timepoints of saliva collection up to 10 hours post-dose. Geometric mean ratios were not calculated after 10 hours. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection. (NCT02640755)
Timeframe: Saliva was collected at 1, 2, 4, 6, 8 and 10 h post [14C]-AZD2014 dose in the Single Dose Period.

Intervention	ng/mL:ngEq/mL (Geometric Mean)
	1 h	2 h	4 h	6 h	8 h	10 h
[14C]-AZD2014 (Period 1 [Day 1 - 8])	1.011	0.8217	0.7001	0.4993	0.4671	0.3648

Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity

The mean ratios of whole blood total radioactivity to plasma total radioactivity are presented for the timepoints of sample collection up to 12 hours post-dose. Geometric mean ratios were not calculated after 12 hours. (NCT02640755)
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h post [14C]-AZD2014 dose.

Intervention	ngEq/mL:ngEq/mL (Geometric Mean)
	0.5 h	1 h	1.5 h	2 h	3 h	4 h	6 h	8 h	12 h
[14C]-AZD2014 (Period 1 [Day 1 - 8])	0.6861	0.6713	0.6825	0.6623	0.6750	0.6904	0.6797	0.6917	0.7211

T(Last) for [14C] Radioactivity in Whole Blood and Saliva

Mean [14C] radioactivity t(last) values in whole blood and saliva following administration of [14C]-AZD2014 on Day 1 are presented. (NCT02640755)
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.

Intervention	h (Geometric Mean)
	t(last) in whole blood	t(last) in saliva
[14C]-AZD2014 (Period 1 [Day 1 - 8])	18.26	15.33

Time to Last Measurable Concentration (t[Last]) for AZD2014 in Plasma and Saliva

AZD2014 t(last) values in plasma and saliva following administration of [14C]-AZD2014 on Day 1 are presented. (NCT02640755)
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.

Intervention	h (Geometric Mean)
	t(last) in plasma	t(last) in saliva
[14C]-AZD2014 (Period 1 [Day 1 - 8])	17.04	10.57

Time to Maximum Observed Concentration (Tmax) for AZD2014 in Plasma and Saliva

AZD2014 Tmax values for plasma and saliva following administration of [14C]-AZD2014 on Day 1 are presented. (NCT02640755)
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.

Intervention	h (Median)
	Tmax in plasma	Tmax in saliva
[14C]-AZD2014 (Period 1 [Day 1 - 8])	0.53	1.00

Tmax for [14C] Radioactivity in Whole Blood and Saliva

[14C] radioactivity tmax in whole blood and saliva following administration of [14C]-AZD2014 on Day 1 is presented . (NCT02640755)
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.

Intervention	h (Median)
	tmax in whole blood	tmax in saliva
[14C]-AZD2014 (Period 1 [Day 1 - 8])	0.53	1.00

Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014

The mean concentrations of total radioactivity in blood collected from each patient who received a single oral dose of 125 mg [14C]-AZD2014 are presented for time points of blood sampling up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours. The total [14C] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose. (NCT02640755)
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h post [14C]-AZD2014 dose in the Single Dose Period.

Intervention	ngEq/mL (Geometric Mean)
	0.5 h (n = 3)	1 h (n = 4)	1.5 h (n = 4)	2 h (n = 4)	3 h (n = 4)	4 h (n = 4)	6 h (n = 4)	8 h (n = 4)	12 h (n = 4)
[14C]-AZD2014 (Period 1 [Day 1 - 8])	2725	2293	1980	1783	1421	1255	964.9	632.1	345.0

Total Radioactivity Concentrations in Saliva Following Administration of [14C]-AZD2014

The mean concentrations of total radioactivity in saliva collected from each patient who received a single oral dose of 125 mg [14C]-AZD2014 are presented for time points of saliva collection up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours. The total [14C] radioactivity in saliva was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose. (NCT02640755)
Timeframe: Saliva was collected at 1, 2, 4, 6, 8, 10 and 12 h post [14C]-AZD2014 dose in the Single Dose Period.

Intervention	ngEq/mL (Geometric Mean)
	1 h (n = 2)	2 h (n = 3)	4 h (n = 3)	6 h (n = 3)	8 h (n = 3)	10 h (n = 3)	12 h (n = 3)
[14C]-AZD2014 (Period 1 [Day 1 - 8])	5495	650.2	264.3	135.4	158.5	105.2	104.0

Total Radioactivity in Plasma Following Administration of [14C]-AZD2014

The mean concentrations of total radioactivity in plasma collected from each patient who received a single oral dose of 125 mg [14C]-AZD2014 are presented for time points of plasma sampling up to 48 hours post-dose. Geometric mean concentrations were not quantifiable after 48 hours. The total [14C] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose. (NCT02640755)
Timeframe: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32 and 48 hours (h) post [14C]-AZD2014 dose in the Single Dose Period.

Intervention	nanogram equivalent/millilitre (ngEq/mL) (Geometric Mean)
	0.5 h (n = 3)	1 h (n = 4)	1.5 h (n = 4)	2 h (n = 4)	3 h (n = 4)	4 h (n = 4)	6 h (n = 4)	8 h (n = 4)	12 h (n = 4)	24 h (n = 4)	32 h (n = 4)	48 h (n = 3)
[14C]-AZD2014 (Period 1 [Day 1 - 8])	4013	3415	2901	2693	2105	1818	1419	914.1	478.6	97.16	45.68	27.21

Safety(Percentage of Participants With Adverse Events and/or Adverse Drug Reactions)

Percentage of patients with AEs. (NCT02447328)
Timeframe: Adverse events were collected from treatment initiation to end of the study about 6 months for each patient.

Intervention	Percentage of participants (Number)
	Adverse Events(AE)	ADR; based on current South Korea label.	Serious AE	Serious ADR	Unexpected AE	Unexpected ADR
Single Arm	81.5	38.3	11.1	0	71.6	24.7

Duration of Response

DOR was defined for responders as the time from the onset of first response to disease progression and for non-responders as zero (NCT00082810)
Timeframe: Up to 4 years

Intervention	months (Median)
Fulvestrant 250 mg + Tipifarnib 300 mg	16

Median Overall Survival

The 95% confidence intervals will be used. (NCT00082810)
Timeframe: From randomization until death or censored at the date of last follow-up, assessed up to 4 years

Intervention	months (Median)
Fulvestrant 250 mg + Tipifarnib 300 mg	19.4

Time to Progression (TTP)

TTP was estimated using the Kaplan-Meier method. (NCT00082810)
Timeframe: From randomization until progression of the disease, assessed up to 4 years

Intervention	months (Median)
Fulvestrant 250 mg + Tipifarnib 300 mg	7.2

Toxicity as Assessed by NCI CTCAE Version 3.0

Number of Participants with serious (grade 3) or life-threatening (grade 4) adverse events (NCT00082810)
Timeframe: Up to 4 years

Intervention	Participants (Count of Participants)
Treatment (Tipifarnib, Fulvestrant)	33

Clinical Benefit Rate (CBR) (CR Rate, PR Rate, and SD)

Number of participants met the definition of Clinical Benefit Rate.Tumor response was assessed every three cycles by CT using RECIST (Response Evaluation Criteria In Solid Tumors) criteria. Per Response Evaluation Criteria in Solid Tumors (RECIST 1.0) for target lesions: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. (NCT00082810)
Timeframe: Up to 24 weeks

Intervention	participants (Number)
	Partial response	Stable disease	Complete response
Fulvestrant 250 mg + Tipifarnib 300 mg	11	5	0

Median Number of Days to Treatment Termination

Time is determined from first dose to termination due to all causes. (NCT00617188)
Timeframe: Up to 373 Days

Intervention	Days (Median)
Fulvestrant Treatment	62

Mean Scores - Quality of Life Assessment

Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O)Version 1/23/07 - This is a relative quality of life assessment; 100 = Best, 0 = Worst. It was developed and validated with cancer patients and includes physical well being, social well being, emotional well being and relationship with doctor subscales and can be summed into one total quality of life score. It is a standardized scale which collects data (scores 1-4) from 47 questions. Answers are transformed into a number between 0-100. Mean was calculated by adding up the values of the scores and dividing by the number of scores. (NCT00617188)
Timeframe: Baseline, 3 Months Post Treatment, 6 Months Post Treatment

Intervention	Scores on a Scale (Mean)
	Baseline (rounded to nearest whole number)	3 Months (rounded to nearest whole number)	6 Months (rounded to nearest whole number)
Fulvestrant Treatment	87	84	81

Patients' Overall 90-Day Clinical Response as Measured by Modified Response Evaluation Criteria in Solid Tumors (Rustin)

Defined by the sum of Complete Responses (CR), Partial Responses (PR) and Stable Disease (SD) in patients treated with fulvestrant. CR=normalization of serum CA-125 level from 2 initially elevated samples, PR=>or=50% decrease in serum CA-125 level from 2 initially elevated samples, Progressive Disease (PD)=CA-125 two times the upper limit of normal on 2 occasions (if previously normalized) OR CA-125 two times nadir (lowest value) on 2 occasions if elevated at initiation of treatment, SD=not CR, PR or PD. (NCT00617188)
Timeframe: Day 90

Intervention	Participants (Number)
	Stable Disease	Progressive Disease (>= 20% increase/new lesions)
Fulvestrant Treatment	13	13

Patients' Overall 90-Day Clinical Response as Measured by Response Evaluation Criteria in Solid Tumors (RECIST)

Best response recorded from the start of treatment until Day 90. Defined by the sum of the Complete Responses (CR), Partial Responses (PR) and Stable Disease (SD) in patients treated with fulvestrant. CR=disappearance of all lesions, PR=>or =30% decrease in sum of all target lesions, Progressive Disease (PD) =>or=20% increase in sum of all target or any new lesions, SD=not CR, PR or PD. (NCT00617188)
Timeframe: Day 90

Intervention	Participants (Number)
	Stable Disease	Progressive Disease (>=20% increase/new lesions)
Fulvestrant Treatment	8	18

Serum Skeletal-Specific Alkaline Phosphatase Concentration

Median Bone mineral results - assessed by serum skeletal-specific alkaline phosphatase laboratory results collected from patients in study. (NCT00617188)
Timeframe: Baseline, 1 Month, 3 Months, 6 Months

Intervention	Units/Liter (Median)
	Alkaline Phosphatase levels - Baseline	Alkaline Phosphatase levels - 1 Month	Alkaline Phosphase levels - 3 Months	Alkaline Phosphase levels - 6 Months
Fulvestrant Treatment	14.0	16.1	18.5	16.2

Urine N-telopeptide Concentration

Median bone mineral results - assessed by serial urine N-telopeptide laboratory results collected from patients. (NCT00617188)
Timeframe: Baseline, 1 Month, 3 Months, 6 Months

Intervention	Units of Bone Collagen Equivalents/mmol (Median)
	Urinary N-telopeptide level - Baseline	Urinary N-telopeptide level - 1 Month	Urinary N-telopeptide level - 3 Months	Urinary N-telopeptide level - 6 Months
Fulvestrant Treatment	50	49	43	46

Number of Participants With Treatment Related Adverse Events as Assessed by CTCAE v4.0

the safety and tolerability of Trastuzumab and Pertuzumab alone and in combination with hormonal therapy or single agent chemotherapy. in HER2+ MBC patients (NCT02000596)
Timeframe: Participants were followed during the study and for 30 days after completion of the study treatment, up to 12 months

Intervention	participants (Number)
	participant 1	participant 2
Cohort 1: T+P	5	5
Cohort 2 - Arm B	2	8

Overall Response Rate (ORR) in Patients

Defined as the total of complete response (CR) defined as a disappearance of all target lesions, partial response (PR) defined as >= 30% decrease in the sum of the longest diameter of target lesions, and stable disease (SD) >= 27 weeks among the total number of participants as defined by the Response Evaluation in Solid Tumors (RECIST) 1.1 response criteria. (NCT02000596)
Timeframe: Participants were staged every two cycles for the duration of the study participation ( CR+PR+SD=ORR), up to 11 months

Intervention	Participants (Count of Participants)
	Complete Response (CR)	Partial Response (PR)	Stable Disease (SD)
Cohort 1: T+P	0	1	1
Cohort 2 - Arm B	0	0	2

Overall Survival (OS)

Overall survival (OS) in treatment cohorts 1 and 2 as well as arms A and B from the time on study until death (NCT02000596)
Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed through study completion, an average of 2 years.

Intervention	Months (Number)
	Subject 1	Subject 2
Cohort 2 - Arm B	25	14

Progression-free Survival (PFS)

Progression Free Survival in treatment cohorts 1 and 2 as well as arms A and B from the time on study until progression of disease or death (NCT02000596)
Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 11 months

Intervention	weeks (Number)
	Subject 1	Subject 2
Cohort 1: T+P	6	24
Cohort 2 - Arm B	12	24

Dose Escalation Phase: Apparent Oral Clearance (CL/F) of Enzalutamide After Single Dosing

Apparent oral clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. (NCT01597193)
Timeframe: pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1

Intervention	liter per hour (Mean)
Dose Escalation: Enzalutamide 80 mg	0.426
Dose Escalation: Enzalutamide 160 mg	0.382

Dose Escalation Phase: Apparent Volume of Distribution (Vz/F) of Enzalutamide After Single Dosing

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. (NCT01597193)
Timeframe: pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1

Intervention	liter (Mean)
Dose Escalation: Enzalutamide 80 mg	151
Dose Escalation: Enzalutamide 160 mg	94.5

Dose-Escalation Phase: Apparent Oral Clearance (CL/F) of Enzalutamide After Multiple Dosing

Intervention	liter per hour (Mean)
Dose Escalation: Enzalutamide 80 mg	0.390
Dose Escalation: Enzalutamide 160 mg	0.507

Dose-Escalation Phase: Area Under the Plasma Concentration-time Curve From Time Zero to 72 Hours (AUC72h) of Enzalutamide After Single Dosing

(NCT01597193)
Timeframe: pre-dose, 0.5, 1, 2, 4, 6, 24, 48 and 72 hours post dose on Day 1

Intervention	micrograms*hour per milliliter (Mean)
Dose Escalation: Enzalutamide 80 mg	43.0
Dose Escalation: Enzalutamide 160 mg	107

Dose-Escalation Phase: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Enzalutamide After Single Dosing

AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). (NCT01597193)
Timeframe: pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1

Intervention	micrograms*hour per milliliter (Mean)
Dose Escalation: Enzalutamide 80 mg	208
Dose Escalation: Enzalutamide 160 mg	478

Dose-Escalation Phase: Percentage of Participants With Dose-limiting Toxicity (DLTs)

DLTs were defined as any of following events related to the study drug: Any adverse event (AE) consistent with a seizure of any grade; Grade greater than equal to (>=) 3 fatigue, diarrhea, nausea, or vomiting that did not improve to Grade 1 within 14 days of initiating standard of care therapy; any Grade >=3 hematologic toxicity with the following modifications: 1) Grade >=3 platelet count associated with bleeding, 2) Grade >=3 absolute neutrophil count that persists for 7 or more days or that was associated with fevers (febrile neutropenia); Grade >=3 any other non-hematological toxicity that was determined to be related to study drug. (NCT01597193)
Timeframe: Baseline up to Day 35

Intervention	percentage of participants (Number)
Dose Escalation: Enzalutamide 80 mg	16.7
Dose Escalation: Enzalutamide 160 mg	0.0

Dose-Escalation Phase: Terminal Elimination Half-Life (t1/2) of Enzalutamide After Single Dosing

Terminal elimination half-life is the time measured for the plasma concentration of Enzalutamide to decrease by one-half of its initial concentration. (NCT01597193)
Timeframe: pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1

Intervention	hours (Mean)
Dose Escalation: Enzalutamide 80 mg	280
Dose Escalation: Enzalutamide 160 mg	198

Dose-Expansion Phase: Trough Plasma Concentration for Enzalutamide

(NCT01597193)
Timeframe: pre-dose on Day 57

Intervention	micrograms per milliliter (Mean)
Dose Expansion: Enzalutamide 160 mg	13.40
Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg	14.33
Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg	13.52
Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg	12.41
Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg	11.62

Percentage of Participants Who Discontinued the Study Drug Due to Adverse Events or Serious Adverse Events

An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. (NCT01597193)
Timeframe: Day 1 up to 30 days after the last dose of study drug or before initiation of a new systemic antitumor treatment, whichever occurred first (up to 3.5 years)

Intervention	percentage of participants (Number)
Dose Escalation: Enzalutamide 80 mg	0.0
Dose Escalation: Enzalutamide 160 mg	0.0
Dose Expansion: Enzalutamide 160 mg	7.1
Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg	5.0
Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg	12.5
Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg	13.0
Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg	0.0

Percentage of Participants Who Require Dose Reductions Due to Adverse Events

Intervention	percentage of participants (Number)
Dose Escalation: Enzalutamide 80 mg	0.0
Dose Escalation: Enzalutamide 160 mg	0.0
Dose Expansion: Enzalutamide 160 mg	0.0
Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg	20.0
Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg	12.5
Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg	8.7
Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg	18.2

Percentage of Participants With Adverse Events of Grade 3 or Higher Severity by National Cancer Institute Common Toxicity Criteria For Adverse Events (NCI CTCAE) (Version 4.03)

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to severity grading based on NCI CTCAE Version 4.03 and defined as Grade 3 AEs = severe or medically significant events but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self-care activities of daily living; Grade 4 AEs = life-threatening, urgent intervention indicated; Grade 5 AEs = death related to adverse event. (NCT01597193)
Timeframe: Day 1 up to 30 days after the last dose of study drug or before initiation of a new systemic antitumor treatment, whichever occurred first (up to 3.5 years)

Intervention	percentage of participants (Number)
Dose Escalation: Enzalutamide 80 mg	57.1
Dose Escalation: Enzalutamide 160 mg	12.5
Dose Expansion: Enzalutamide 160 mg	21.4
Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg	30.0
Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg	37.5
Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg	39.1
Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg	36.4

Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)

An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose of study drug that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious adverse events. (NCT01597193)
Timeframe: Day 1 up to 30 days after the last dose of study drug or before initiation of a new systemic antitumor treatment, whichever occurred first (up to 3.5 years)

Intervention	percentage of participants (Number)
Dose Escalation: Enzalutamide 80 mg	28.6
Dose Escalation: Enzalutamide 160 mg	12.5
Dose Expansion: Enzalutamide 160 mg	14.3
Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg	5.0
Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg	31.3
Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg	13.0
Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg	18.2

Dose-Escalation Phase: Accumulation Ratio of AUC24 of Enzalutamide and Its Metabolites After Multiple Dosing

Accumulation Ratio was defined as the ratio of AUC24 of Day 50 to AUC24 of Day 1, where AUC24 was area under the plasma concentration-time curve from time zero to 24 hours post-dose. Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide. (NCT01597193)
Timeframe: pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 1 and 50

Intervention	ratio (Mean)
	Enzalutamide	M1	M2
Dose Escalation: Enzalutamide 160 mg	9.39	68.0	77.8
Dose Escalation: Enzalutamide 80 mg	17.9	47.6	157

Dose-Escalation Phase: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Enzalutamide and Its Metabolites After Multiple Dosing

Area under the plasma concentration versus time-curve from time zero to end of dosing interval (AUCtau), where dosing interval was 24 hours. Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide. (NCT01597193)
Timeframe: pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50

Intervention	milligram*hour per milliliter (Mean)
	Enzalutamide	M1	M2
Dose Escalation: Enzalutamide 160 mg	325	120	317
Dose Escalation: Enzalutamide 80 mg	207	33.0	140

Dose-Escalation Phase: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC24h) of Enzalutamide and Its Metabolites After Single Dose

Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide. (NCT01597193)
Timeframe: pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post dose on Day 1

Intervention	micrograms*hour per milliliter (Mean)
	Enzalutamide	M1	M2
Dose Escalation: Enzalutamide 160 mg	41.6	1.20	2.76
Dose Escalation: Enzalutamide 80 mg	17.3	0.632	1.13

Dose-Escalation Phase: Maximum Plasma Concentration (Cmax) of Enzalutamide and Its Metabolites After Multiple Dosing

Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide. (NCT01597193)
Timeframe: pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50

Intervention	micrograms per milliliter (Mean)
	Enzalutamide	M1	M2
Dose Escalation: Enzalutamide 160 mg	15.3	6.24	14.1
Dose Escalation: Enzalutamide 80 mg	11.6	1.77	6.42

Dose-Escalation Phase: Maximum Plasma Concentration (Cmax) of Enzalutamide and Its Metabolites After Single Dose

Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide. (NCT01597193)
Timeframe: pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1

Intervention	micrograms per milliliter (Mean)
	Enzalutamide	M1	M2
Dose Escalation: Enzalutamide 160 mg	4.01	0.0707	0.184
Dose Escalation: Enzalutamide 80 mg	1.90	0.0375	0.0879

Dose-Escalation Phase: Peak-to-Trough Ratio of Enzalutamide and Its Metabolites After Multiple Dosing

Peak-to-trough ratio was calculated by dividing Cmax with Cmin of Enzalutamide and its Metabolites. Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide. Cmax was maximum plasma concentration during the dosing interval and Cmin was minimum observed plasma concentration during the dosing interval. (NCT01597193)
Timeframe: pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50

Intervention	ratio (Mean)
	Enzalutamide	M1	M2
Dose Escalation: Enzalutamide 160 mg	1.14	1.42	1.00
Dose Escalation: Enzalutamide 80 mg	1.39	1.32	0.999

Dose-Escalation Phase: Time to Reach Maximum Plasma Concentration (Tmax) of Enzalutamide and Its Metabolites After Multiple Dosing

Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide. (NCT01597193)
Timeframe: pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Day 50

Intervention	hours (Median)
	Enzalutamide	M1	M2
Dose Escalation: Enzalutamide 160 mg	1.00	2.29	0.58
Dose Escalation: Enzalutamide 80 mg	0.500	5.70	24.0

Dose-Escalation Phase: Time to Reach Maximum Plasma Concentration (Tmax) of Enzalutamide and Its Metabolites After Single Dosing

Carboxylic Acid (M1) and N-desmethyl (M2) are two metabolites of Enzalutamide. (NCT01597193)
Timeframe: pre-dose, 0.5, 1, 2, 4, 6, 24, 48, 72 and 96 hours post dose on Day 1

Intervention	hours (Median)
	Enzalutamide	M1	M2
Dose Escalation: Enzalutamide 160 mg	1.00	23.1	23.7
Dose Escalation: Enzalutamide 80 mg	0.500	24.1	23.9

Percentage of Participants With Potentially Clinically Significant Change From Baseline in Vital Signs

Absolute systolic blood pressure (SBP) greater than (>) 180 millimeter of mercury (mm Hg) and an increase of >40 mm Hg from baseline; absolute SBP less than (<) 90 mm Hg and an decrease of >30 mm Hg from baseline. Absolute diastolic blood pressure (DBP) >105 mm Hg and an increase of >30 mm Hg from baseline; absolute DBP <50 mm Hg and an increase of >20 mm Hg from baseline. Absolute heart rate >120 beats per minute (bpm) and an increase of >30 bpm from baseline; absolute heart rate <50 bpm and decrease of >20 bpm from baseline. Participants with any of these abnormalities were reported for this outcome in each arm. (NCT01597193)
Timeframe: Day 1 up to 30 days after the last dose of study drug or before initiation of a new systemic antitumor treatment, whichever occurred first (up to 3.5 years)

,,,,,,

Intervention	percentage of participants (Number)
	Blood pressure	Heart rate
Dose Escalation: Enzalutamide 160 mg	0	2
Dose Escalation: Enzalutamide 80 mg	1	0
Dose Expansion: Enzalutamide 160 mg	1	1
Dose Expansion: Enzalutamide 160 mg + Anastrozole 1 mg	0	0
Dose Expansion: Enzalutamide 160 mg + Exemestane 25 mg	1	0
Dose Expansion: Enzalutamide 160 mg + Exemestane 50 mg	2	0
Dose Expansion: Enzalutamide 160 mg + Fulvestrant 500 mg	1	0

Objective Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment

The Percentage of Patients Who Experience an Objective Benefit From Treatment (CR+PR). The response categories were assigned using RECIST criteria. Complete Response (CR) = Disappearance of all target lesions ; Partial Response (PR) = >=30% decrease in the sum of the longest diameter of target lesions. (NCT00405938)
Timeframe: 18 months

Intervention	Participants (Count of Participants)
Bevacizumab/Anastrozole	18
Bevacizumab/Fulvestrant	11

Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease

Progression Free Survival (PFS) is defined as the interval, in months, from the date of first treatment to the date of disease progression or death, whichever occurred first. (NCT00405938)
Timeframe: 18 months

Intervention	months (Median)
Bevacizumab/Anastrozole	21
Bevacizumab/Fulvestrant	9

Clinical Benefit Rate

Response to treatment with fulvestrant in terms of Clinical Benefit Rate. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or TC: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; PD (progressive disease)> = 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion or the appearance of new lesions; Clinical Benefit = CR + PR+ Stable Disease (not progression of the disease for 24 or more weeks). (NCT01509625)
Timeframe: 22 months

Intervention	percentage of patients (Number)
One Arm of Metastatic Breast Cancer Patients	56.5

Duration of Clinical Benefit

"Response to treatment with fulvestrant in terms of Duration of the Clinical Benefit.~Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or TC: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; PD (progressive disease)> = 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion or the appearance of new lesions; Clinical Benefit = CR + PR+ Stable Disease (not progression of the disease for 24 or more weeks)." (NCT01509625)
Timeframe: 22 months

Intervention	month (Median)
Patients With Clinical Benefit	18.4

Overall Survival

Response to treatment with fulvestrant in terms of Overall Survival (NCT01509625)
Timeframe: 22 months

Intervention	month (Median)
One Arm of Metastatic Breast Cancer Patients	43.2

Progression Free Survival

"Response to treatment with fulvestrant (Faslodex®) in terms of Progression Free Survival.~Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% or more increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions." (NCT01509625)
Timeframe: 22 months

Intervention	month (Median)
One Arm of Metastatic Breast Cancer Patients	10.6

Response to Treatment With Fulvestrant in Terms of PFS in a Subgroup of Patients After a First-line Hormonal Therapy Prior and in Subgroup of Patients After Two or More Prior Lines of Hormonal Therapy

To assess the response to treatment with fulvestrant (Faslodex®) at the 500 mg/month and LD-500 dose in terms of PFS in a subgroup of patients after a first-line hormonal therapy prior and in subgroup of patients after two or more prior lines of hormonal therapy (NCT01509625)
Timeframe: 22 months

Intervention	month (Median)
Previous Treatment Wiht One Line of Hormonal Treatment	11.2
Previous Treatment With Two or More Hormonal Treatment Lines	9.2

Response to Treatment With Fulvestrant in Terms of PFS in a Subgroup of Patients With Elevated Ki-67 and With Low Ki-67

To assess the response to treatment with fulvestrant (Faslodex®) at the 500 mg/month and LD-500 dose in terms of PFS in a subgroup of patients with elevated ki-67 (greater than or equal to 20%) and with low ki-67 and to compare both groups (NCT01509625)
Timeframe: 22 months

Intervention	month (Median)
Patients With Tumors ki67 Positive	9.6
Patients With Tumors ki67 Negative	10.0

Response to Treatment With Fulvestrant in Terms of PFS in a Subgroup of Patients With Visceral Metastases and Without Visceral Metastases

"Response to treatment with fulvestrant at the 500 mg/month and LD 500 dose in terms of PFS in a subgroup of patients with visceral metastases and without visceral metastases.~Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or TC: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; PD (progressive disease)> = 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion or the appearance of new lesions; Clinical Benefit = CR + PR+ Stable Disease (not progression of the disease for 24 or more weeks)." (NCT01509625)
Timeframe: 22 months

Intervention	month (Median)
Patients Without Visceral Metastasis	10.6
Patients With Visceral Metastasis	10

Response to Treatment With Fulvestrant in Terms of PFS in Subgroups of Patients With Her-2 Overexpression and Those Who do Not Over-express Her-2

"To assess the response to treatment with fulvestrant at the 500 mg/month and LD 500 dose in terms of PFS in subgroups of patients with her-2 overexpression (+++ by immunohistochemistry or FISH positive) and those who do not over-express her-2 and to compare both groups.~Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or TC: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; PD (progressive disease)> = 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion or the appearance of new lesions; Clinical Benefit = CR + PR+ Stable Disease (not progression of the disease for 24 or more weeks)." (NCT01509625)
Timeframe: 22 months

Intervention	month (Median)
Patients With Tumors HER2 Positive	10.2
Patients With Tumors HER2 Negative	10.3

Number of Participants With Adverse Events

(NCT01509625)
Timeframe: 22 months

Intervention	percentage of patients (Number)
	any toxicity	local pain injection	Muscle-bone pain	Gastrointestinals disorders	Hot flashes	Urinary infection	Weight gain	Vaginitis	Joint pain
One Arm of Metastatic Breast Cancer Patients	35.4	9.9	7.2	6.8	6.1	0.8	0.8	0.4	16

Number of Participants With Progression-free Survival at 4 Months

Progression-free survival rate is defined as the proportion of subjects who are progression free (CR, PR and SD) at 4 months after initiating treatment with sorafenib plus fulvestrant. Complete Response (CR):Disappearance of all target (both measurable and evaluable)lesions. Partial Response (PR):At least a 30% decrease in the sum of the longest diameter (LD) of both measurable and evaluable target lesions. Stable Disease (SD):Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease(PD). (NCT00722072)
Timeframe: 4 months after initiating treatment with sorafenib plus fulvestrant.

Intervention	Participants (Number)
Sorafenib and Fulvestrant	6

Clinical Benefit Rate

Clinical benefit rate is defined as number of patients with objective response (complete response or partial response) or stable disease for at least 24 weeks divided by number of patients randomized in each arm. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR) is defined as >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease; Complete Response (CR) is defined as disappearance of all target lesions. (NCT01797120)
Timeframe: Every 3 months until progression or up to 3 years

Intervention	proportion of patients (Number)
Fulvestrant & Everolimus	0.636
Fulvestrant & Placebo	0.415

Objective Response Rate

Objective response rate is defined as number of patients with complete or partial response (by Physical Exam, CT or MRI) divided by number of patients randomized in each arm (NCT01797120)
Timeframe: Every 3 months until progression or up to 3 years

Intervention	proportion of patients (Number)
Fulvestrant & Everolimus	0.182
Fulvestrant & Placebo	0.123

Overall Survival

Overall survival will be characterized using Kaplan-Meier plots and other descriptive metrics. (NCT01797120)
Timeframe: Every 3 months until progression or up to 3 years

Intervention	months (Median)
Fulvestrant & Everolimus	28.3
Fulvestrant & Placebo	31.4

Progression-free Survival

Progression-free survival documented by Physical Exam, CT Scan or MRI in post-menopausal patients with hormone-receptor positive metastatic breast cancer that is resistant to aromatase inhibitor therapy treated with fulvestrant and everolimus compared to fulvestrant alone from randomization to documented disease progression or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT01797120)
Timeframe: Every 3 months until progression or up to 3 years

Intervention	months (Median)
Fulvestrant & Everolimus	10.3
Fulvestrant & Placebo	5.1

Number of Participants With Progressive Disease at Day +90

Progressive Disease is defined as failure to achieve a statistically significant decrease in PSA rise after the day +90 PSA value (NCT00217464)
Timeframe: 90, 60, and 30 days pre-treatment, the day of start therapy (day 0) and 30, 60 and 90 days post-treatment

Intervention	participants (Number)
Fulvestrant	15

Proportion of Patients Who Respond to Treatment.

Response is defined to be the clear slowing of the rate of increase of PSA levels with time (NCT00217464)
Timeframe: 90, 60, and 30 days pre-treatment, the day of start therapy (day 0) and 30, 60 and 90 days post-treatment

Intervention	percentage of participants (Number)
Fulvestrant	0

Overall Survival (OS) - Full Analysis Set (FAS)

Overall Survival (OS) is defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last known date patient alive. Patients were followed up approximately every 6 weeks after randomization and every 3 months during survival follow-up. (NCT01633060)
Timeframe: Every 6 weeks after randomization up to a maximum of 5 years

Intervention	Months (Median)
BKM120 100mg + Fulvestrant	21.2
Placebo + Fulvestrant	22.1

Progression Free Survival (PFS) Based on Local Investigator Assessment - Full Analysis Set (FAS)

Progression Free Survival (PFS) is defined as the time from date of randomization to the date of first radiologically documented progression or death due to any cause. If a patient did not progress or die at the time of the analysis data cut-off or start of new antineoplastic therapy, PFS was censored at the date of the last adequate tumor assessment before the earliest of the cut-off date or the start date of additional anti-neoplastic therapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria RECIST v1.1, as 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline and/or unequivocal progression of the non-target lesions and/or appearance of a new lesion. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm. Patients were followed up for approximately every 6 weeks after randomization. (NCT01633060)
Timeframe: Every 6 weeks after randomization up to a maximum of 4 years

Intervention	Months (Median)
BKM120 100mg + Fulvestrant	3.9
Placebo + Fulvestrant	1.8

Time to Definitive Deterioration of ECOG Performance Status From Baseline - Full Analysis Set (FAS)

The Eastern Cooperative Oncology Group (ECOG) Performance Status is a scale used to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis. The ECOG Performance Scores has 5 grades: 0 = fully active, able to carry on all pre-disease performance without restriction, 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work, 2 = ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours, 3 = capable of only limited self-care, confined to bed or chair more than 50% of waking hours, 4 = completely disabled, cannot carry on any self-care, totally confined to bed or chair and 5 = dead. Definitive deterioration is defined as no improvement in the ECOG status following observation of the deterioration. (NCT01633060)
Timeframe: Screening, Baseline (Cycle 1 Day 1) and then at day 1 of each cycle and at the EOT visit

Intervention	Months (Median)
BKM120 100mg + Fulvestrant	18.3
Placebo + Fulvestrant	12.0

Clinical Benefit Rate (CBR) by PIK3CA Mutational Status

Clinical Benefit Rate (CBR) is defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) or Non-CR/non-PD lasting more than 14 or 24 weeks based on local investigator's assessment according to RECIST 1.1. CBR was analyzed in the full population and by PIK3CA mutational status based on ctDNA. Patients were followed up for the duration of the study and approximately every 6 weeks after randomization. (NCT01633060)
Timeframe: Week 14, Week 24

Intervention	Percentage of Participants (Number)
	CBR>=14wks(FAS)	CBR>=24wks(FAS)	CBR>=14wks(FAS ctDNA PIK3CA mutant)	CBR>=24wks(FAS ctDNA PIK3CA mutant)	CBR>=14wks(FAS ctDNA PIK3CA non-mutant)	CBR>= 24wks(FAS ctDNA PIK3CA non-mutant)
BKM120 100mg + Fulvestrant	33.2	24.6	38.0	30.0	36.4	25.8
Placebo + Fulvestrant	20.3	15.4	14.3	11.4	21.0	14.8

Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30 - Full Analysis Set (FAS)

The global health status/QoL scale score of the QLQ-C30 is identified as the primary PRO variable of interest. Physical Functioning (PF), Emotional Functioning (EF) and Social Functioning (SF) scale scores of the QLQ-C30. The time to definitive 10% deterioration is defined as the time from the randomization date to the date of an event, which is defined as a worsening (decrease) in score by at least 10% compared to baseline, with no later increase above this threshold observed during the course of the study or death due to any cause. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high /healthy level of functioning, a high score for the global health status / QoL represents a high QoL. (NCT01633060)
Timeframe: Baseline, Week 6 (C2D15), Week 12 (C4D1), then every 8 weeks until discontinuation (a cycle [C] = 4 weeks) up to 5 years.

Intervention	Months (Median)
	EORTC QLQ-30 - Global QoL score	EORTC QLQ-30 - PF scale score	EORTC QLQ-30 - EF scale score	EORTC QLQ-30 - SF scale score
BKM120 100mg + Fulvestrant	5.3	11.8	10.0	10.0
Placebo + Fulvestrant	6.3	10.1	10.0	11.5

Long-term Safety and Tolerability in the Two Treatment Arms - Safety Set (SS)

Analysis of frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths. (NCT01633060)
Timeframe: From first dose of study treatment to 30 days after last dose of study treatment, up to 5 years

Intervention	Percentage of Participants (Number)
	AEs	SAEs	Deaths
BKM120 100mg + Fulvestrant	97.9	25.7	42.7
Placebo + Fulvestrant	92.9	18.6	48.6

Overall Response Rate (ORR) by PIK3CA Mutational Status

Overall Response Rate (ORR) is defined as the proportion of participants with best overall response of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST 1.1. ORR was analyzed in the full population and by PIK3CA mutational status based on ctDNA. Response Evaluation Criteria in Solid Tumors (RECIST v1.1) for target/non target lesions: Complete Response (CR), disappearance of all target/non target lesions (all lymph nodes assigned as non-target lesions must be non-pathological in size (< 10 mm short axis)); Partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions ; Overall Response (OR)= CR+PR. Patients were followed up for the duration of the study and for approximately every 6 weeks after randomization. (NCT01633060)
Timeframe: Every 6 weeks after randomization up to a maximum of 5 years

Intervention	Percentage of Participants (Number)
	Full Analysis Set (FAS)	FAS ctDNA PIK3CA mutant	FAS ctDNA PIK3CA non-mutant
BKM120 100mg + Fulvestrant	7.6	10.0	7.6
Placebo + Fulvestrant	2.1	0	3.7

Overall Survival (OS) by PIK3CA Mutational Status

Overall Survival (OS) by PIK3CA mutational status based on ctDNA is defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last known date patient alive. Patients were followed up approximately every 6 weeks after randomization and every 3 months during survival follow-up. (NCT01633060)
Timeframe: Every 6 weeks after randomization up to a maximum of 5 years

Intervention	Months (Median)
	FAS ctDNA PIK3CA mutant	FAS ctDNA PIK3CA non-mutant
BKM120 100mg + Fulvestrant	21.8	21.4
Placebo + Fulvestrant	NA	21.4

Plasma Concentration-time Profiles of BKM120 in Combination With Fulvestrant at Cycle 1 Day 1 - Pharmacokinetic Analysis Set (PAS)

Plasma samples were collected from the first 100 BKM120-treated patients on Cycle 1 Day 1 (at 1h, 2h, and 6h post-dose and a recommended 9h post-dose sample). (NCT01633060)
Timeframe: C1D1 1 hour post dose, C1D1 2 hour post dose, C1D1 6 hour post dose and C1D1 9 hour post dose

Intervention	nanogram per milliliter (ng/mL) (Geometric Mean)
	C1D1 - 1 hour post dose	C1D1 - 2 hour post dose	C1D1 - 6 hour post dose	C1D1 - 9 hour post dose
BKM120 100mg + Fulvestrant	425.178	615.441	314.094	302.899

Predose Trough Concentration-time Profile of BKM120 in Combination With Fulvestrant Over Time - Pharmacokinetic Analysis Set (PAS)

Pre-dose samples were collected for trough concentrations at Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1 and Cycle 4 Day 1. (NCT01633060)
Timeframe: C1D15, C2D1, C3D1 and C4D1

Intervention	nanogram per milliliter (ng/mL) (Geometric Mean)
	C1D15	C2D1	C3D1	C4D1
BKM120 100mg + Fulvestrant	939.978	880.074	777.026	1088.074

Progression Free Survival (PFS) by PIK3CA Mutational Status

Intervention	Months (Median)
	FAS ctDNA PIK3CA mutant	FAS ctDNA PIK3CA non-mutant
BKM120 100mg + Fulvestrant	4.2	3.9
Placebo + Fulvestrant	1.6	2.7

Cohort A: Median Progression-Free Survival (PFS)

Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. (NCT02657343)
Timeframe: Disease was evaluated radiologically every cycles on treatment and in long-term follow-up every 12 weeks. Median follow-up in this study cohort was 12.4 months.

Intervention	Months (Median)
Cohort A: Ribociclib + T-DM1	10.4

Cohort A: Objective Response Rate (ORR)

"Objective response rate(ORR) was defined as the portion of patients with complete response or partial response by RECIST 1.1 criteria.~Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters." (NCT02657343)
Timeframe: Disease was evaluated radiologically at baseline and each cycle on treatment; Treatment continued until disease progression or unacceptable toxicity. Median treatment duration was 10.9 months with range 2.5 - 19.3 months.

Intervention	percentage of participants (Number)
Cohort A: Ribociclib + T-DM1	16.7

Cohort A: Recommended Phase2 Dose (RP2D)

Standard 3+3 phase-I design will be utilized in this trial. Briefly, a minimum of 3 evaluable patients will be entered at first dose level (=300 mg ribociclib) and T-DM1 (3.6 mg/kg IV). If 1 out of the first 3 patients enrolled experiences a dose-limiting toxicity (DLT), 3 additional patients will be enrolled to that dose level. If no more than 1 patient in 6 experiences a DLT, dose escalation of ribociclib will continue to next dose-level. If 2 or more patients at any given dose level experience a DLT, dose escalation will stop and the Recommended Phase2 Dose (RP2D) will be defined. Maximum dose-escalation of Ribociclib (LEE011) will be up to 600 mg. (NCT02657343)
Timeframe: Disease was evaluated at baseline and each cycle on treatment and the end of treatment. Toxicity was evaluated each cycle on treatment, end of treatment and 30 days follow-up. Median treatment duration was 10.9 months with range 2.5 - 19.3 months.

Intervention	mg (Number)
Cohort A: Ribociclib + T-DM1	400

Cohort B: Median Progression-Free Survival (PFS)

Intervention	Months (Median)
Cohort B: Ribociclib + Trastuzumab	1.33

Cohort B: Objective Response Rate (ORR)

Intervention	rate (Number)
Cohort B: Ribociclib + Trastuzumab	0

Cohort B: Overall Survival (OS)

OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive. (NCT02657343)
Timeframe: Participants were followed long-term for survival every 12 weeks from the end of treatment until death or lost to follow-up. Median follow-up in this study cohort was 5 months.

Intervention	Months (Number)
Cohort B: Ribociclib + Trastuzumab	7.9

Cohort A: Incidence of Grade 3 Treatment-Related Toxicity

All grade 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 4 AE of any type during the time of observation. (NCT02657343)
Timeframe: Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. median follow-up is 12.4 months

Intervention	number of incidences (Number)
	neutropenia	leukopenia	anemia	lymphopenia	thrombocytopenia	febrile neutropenia
Cohort A: Ribociclib + T-DM1	4	4	3	2	2	1

Cohort B: Incidence of Grade 3 Treatment-Related Toxicity

Intervention	number of incidences (Number)
	neutropenia	fatigue	pain
Cohort B: Ribociclib + Trastuzumab	2	1	1

Progression-Free Survival (PFS), as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)

PFS was defined as the time from randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first). Disease progression was defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions. (NCT04576455)
Timeframe: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to a clinical cutoff of 15 months)

Intervention	months (Median)
Giredestrant	5.55
Physician's Choice of Endocrine Monotherapy	5.36

Investigator-Assessed PFS, in Subgroups Categorized by Estrogen Receptor 1 (ESR1) Mutation Status

PFS was defined as the time from randomization to the first occurrence of disease progression determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first). Disease progression was defined as ≥20% increase in in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions. Investigator-assessed PFS was analyzed in subgroups categorized by baseline ESR1 mutation status (i.e., with or without ESR1 mutation at baseline) from plasma circulating tumor deoxyribonucleic acid (ctDNA). (NCT04576455)
Timeframe: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to a clinical cutoff of 15 months)

Intervention	months (Median)
	PFS by ESR1 Mutation Detected at Baseline	PFS by ESR1 Mutation Not Detected at Baseline
Giredestrant	5.32	7.20
Physician's Choice of Endocrine Monotherapy	3.48	6.60

Clinical Benefit Rate

Proportion of participants who have confirmed and unconfirmed partial response, complete response or stable disease. (NCT02137837)
Timeframe: assessed every 12 weeks, up to 5 years

Intervention	percentage of participants (Number)
Arm 1: Fulvestrant + Everolimus Placebo + Anastrozole Placebo	69
Arm 2: Fulvestrant + Everolimus + Anastrozole Placebo	83
Arm 3: Fulvestrant + Everolimus + Anastrozole	67

Molecular Determinants of Response in Circulating Tumor Cells: CTC-ETI

CTC-Endocrine Therapy Index (CTC-ETI) on the CellSearch® platform. Based on enumeration of CTC/7.5 mL of whole blood, with >= 5 being elevated. (Due to limited samples collected, full analysis was not able to be performed as planned, so outcome measure reported here is number with elevated Day 1 CTC.) (NCT02137837)
Timeframe: Day 1, Day 29, time of progression (Day 29 to be collected only if Day 1 CTC was elevated.)

Intervention	Participants (Count of Participants)
Arm 1: Fulvestrant + Everolimus Placebo + Anastrozole Placebo	1
Arm 2: Fulvestrant + Everolimus + Anastrozole Placebo	1
Arm 3: Fulvestrant + Everolimus + Anastrozole	0

Overall Survival

From date of registration to date of death due to any cause. Participants last known to be alive without report of progression are censored at date of last contact. (NCT02137837)
Timeframe: up to 5 years

Intervention	months (Median)
Arm 1: Fulvestrant + Everolimus Placebo + Anastrozole Placebo	46.8
Arm 2: Fulvestrant + Everolimus + Anastrozole Placebo	56.6
Arm 3: Fulvestrant + Everolimus + Anastrozole	33.6

Progression Free Survival (Fulvestrant + Everolimus vs Fulvestrant + Everolimus + Anastrozole)

From date of registration to date of first documentation of progression or death due to any cause. Participants last known to be alive without report of progression are censored at date of last contact. (NCT02137837)
Timeframe: up to 5 years

Intervention	months (Median)
Arm 2: Fulvestrant + Everolimus + Anastrozole Placebo	11.3
Arm 3: Fulvestrant + Everolimus + Anastrozole	9.90

Progression-free Survival (Fulvestrant Versus Fulvestrant + Everolimus + Anastrozole)

Intervention	months (Median)
Arm 1: Fulvestrant + Everolimus Placebo + Anastrozole Placebo	14.0
Arm 3: Fulvestrant + Everolimus + Anastrozole	9.9

Progression-Free Survival (Fulvestrant vs Fulvestrant + Everolimus )

From date of registration to date of first documentation of progression or death due to any cause. Participants last known to be alive are censored at date of last contact. (NCT02137837)
Timeframe: up to 5 years

Intervention	months (Median)
Arm 1: Fulvestrant + Everolimus Placebo + Anastrozole Placebo	14.0
Arm 2: Fulvestrant + Everolimus + Anastrozole Placebo	11.3

Response Rate

Proportion of participants who have confirmed or unconfirmed partial or complete response to therapy (NCT02137837)
Timeframe: assessed every 12 weeks, up to 5 years

Intervention	percentage of participants (Number)
Arm 1: Fulvestrant + Everolimus Placebo + Anastrozole Placebo	22
Arm 2: Fulvestrant + Everolimus + Anastrozole Placebo	60
Arm 3: Fulvestrant + Everolimus + Anastrozole	44

Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs

Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported. (NCT02137837)
Timeframe: Duration of treatment and follow up until death or 5 years post registration

Intervention	Participants (Number)
	Abdominal pain	Anorexia	Aspartate aminotransferase increased	Dehydration	Diarrhea	Fatigue	Flu like symptoms	Generalized muscle weakness	Hyperglycemia	Hypertension	Hypocalcemia	Hypokalemia	Hyponatremia	Hypophosphatemia	Hypotension	Localized edema	Lymphocyte count decreased	Mucositis oral	Neutrophil count decreased	Rash maculo-papular	Resp, thoracic and mediastinal disorders - Other	Sore throat	Thromboembolic event	Vomiting	White blood cell decreased
Arm 1: Fulvestrant + Everolimus Placebo + Anastrozole Placebo	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Arm 2: Fulvestrant + Everolimus + Anastrozole Placebo	1	1	1	2	1	2	1	1	1	2	1	2	1	1	0	1	1	0	2	0	1	0	0	1	1
Arm 3: Fulvestrant + Everolimus + Anastrozole	0	1	0	1	0	0	0	0	0	2	0	1	0	0	1	0	0	1	0	1	0	1	1	0	0

Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30

The global health status/QoL scale score of the QLQ-C30 is identified as the primary PRO variable of interest. Physical Functioning (PF), Emotional Functioning (EF) and Social Functioning (SF) scale scores of the QLQ-C30. The time to definitive 10% deterioration is defined as the time from the randomization date to the date of an event, which is defined as a worsening (decrease) in score by at least 10% compared to baseline, with no later increase above this threshold observed during the course of the study or death due to any cause. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high /healthy level of functioning, a high score for the global health status / QoL represents a high QoL. Patients were assessed up to approx. 8.3 months. Only descriptive analysis performed. (NCT01610284)
Timeframe: Cycle 1 day 1, cycle 1 day 15, 6 weeks after randomisation and then every 8 weeks until end of treatment

Intervention	Months (Median)
BKM120 100mg + Fulvestrant	7.10
Placebo + Fulvestrant	11.50

Median Time to Definitive Deterioration of the ECOG Performance Status - Full Analysis Set (FAS)

Time to definitive deterioration of the ECOG PS was defined as the time between the date of randomization and the date of the assessment at which definitive deterioration was seen. Only descriptive analysis performed. (NCT01610284)
Timeframe: Up to approx 27 months

Intervention	Months (Median)
BKM120 100mg + Fulvestrant	24.0
Placebo + Fulvestrant	26.4

Clinical Benefit Rate (CBR) - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort

Clinical Benefit Rate (CBR) is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) or Non-CR/non-PD lasting more than 24 weeks based on local investigator's assessment according to RECIST 1.1. CBR was analyzed in the full population. Only descriptive analysis performed. (NCT01610284)
Timeframe: From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 5 years

Intervention	Percentage of Participants (Number)
	FAS-Full population	FAS-Main cohort	FAS-PI3K pathway activated	FAS-PI3K pathway non-activated	FAS-PI3K pathway unknown
BKM120 100mg + Fulvestrant	43.8	41.7	40.4	42.7	49.7
Placebo + Fulvestrant	42.0	39.6	40.8	38.8	49.0

Number of Participants With On-Treatments Adverse Events, Serious Adverse Events and Deaths

Analysis of frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths. Only descriptive analysis performed. (NCT01610284)
Timeframe: From first dose of study treatment to 30 days after last dose of study treatment, assessed for approximately 5 years

Intervention	Participants (Count of Participants)
	On-treatment Adverse Event (AEs)	On-treatment Serious Adverse Event (SAEs)	On-treatment Deaths	Primary cause of Death = Study Indication	Primary cause of Death = Unknown reason	Primary cause of Death = Disease Progression	Primary cause of Death = Pneumonia	Primary cause of Death = Septic Shock	Primary cause of Death = Cerebral Haemorrhage	Primary cause of Death = Cerebral Accident	Primary cause of Death = Sudden Death	Primary cause of Death = Urosepsis
BKM120 100mg + Fulvestrant	569	144	12	6	2	2	1	1	0	0	0	0
Placebo + Fulvestrant	532	101	13	7	0	2	0	0	1	1	1	1

Overall Response Rate (ORR) - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort

Overall Response Rate (ORR) is defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST 1.1. ORR was analyzed in the full population. Response Evaluation Criteria in Solid Tumors (RECIST v1.1) for target/non target lesions: Complete Response (CR), disappearance of all target/non target lesions (all lymph nodes assigned as non-target lesions must be non-pathological in size (< 10 mm short axis)); Partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions ; Overall Response (OR)= CR+PR. Only descriptive analysis performed. (NCT01610284)
Timeframe: From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 5 years

Intervention	Percentage of Participants (Number)
	FAS-Full population	FAS-Main cohort	FAS-PI3K pathway activated	FAS-PI3K pathway non-activated	FAS-PI3K pathway unknown
BKM120 100mg + Fulvestrant	11.8	11.0	10.6	11.3	14.1
Placebo + Fulvestrant	7.7	7.8	8.2	7.5	7.5

Overall Survival (OS) - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort

Overall Survival (OS) is defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last known date patient alive. Patients were followed up for the duration of the study and for an expected average of every 3 months after end of treatment. (NCT01610284)
Timeframe: Every 3 months following end of treatment visit, assessed for approximately 5 years

Intervention	Months (Median)
	FAS-Full population	FAS-Main cohort	FAS-PI3K pathway activated	FAS-PI3K pathway non-activated	FAS-PI3K pathway unknown
BKM120 100mg + Fulvestrant	33.2	30.9	33.6	28.8	42.3
Placebo + Fulvestrant	30.4	28.9	27.5	30.0	36.0

Plasma Concentration-time Profiles of BKM120 in Combination With Fulvestrant at Cycle 2 Day 1

Plasma samples were collected from the first 200 BKM120-treated patients on Cycle 2 Day 1 (at pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h and 24h [before Cycle 2 Day 2 dose] post-dose). Each cycle is 28 days. Only descriptive analysis performed. (NCT01610284)
Timeframe: Cycle2 Day1 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours post-dose). Each cycle is 28 days.

Intervention	nanogram per milliliter (ng/mL) (Geometric Mean)
	C2D1 0hr (predose)	C2D1 0.5hr	C2D1 1hr	C2D1 1.5hr	C2D1 2hr	C2D1 3hr	C2D1 4hr	C2D1 6hr	C2D1 8hr	C2D1 24hr
BKM120 100mg + Fulvestrant	768.306	750.767	988.341	1082.086	1099.517	1081.123	935.485	795.555	808.886	712.336

Predose Trough Concentration-time Profile of BKM120 in Combination With Fulvestrant Over Time - Pharmacokinetic Analysis Set (PAS)

Pre-dose samples were collected for trough concentrations at Cycle 2 Day 1, Cycle 2 Day 15 and Cycle 3 Day 1. Each cycle is 28 days. Only descriptive analysis performed. (NCT01610284)
Timeframe: Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1. Each cycle is 28 days.

Intervention	nanogram per milliliter (ng/mL) (Geometric Mean)
	Cycle 2 Day 1	Cycle 2 Day 15	Cycle 3 Day 1
BKM120 100mg + Fulvestrant	733.278	735.172	716.414

Progression Free Survival (PFS) Based on Local Investigator Assessment - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort

Progression Free Survival (PFS) is defined as the time from date of randomization to the date of first radiologically documented progression or death due to any cause. If a patient did not progress or die at the time of the analysis data cut-off or start of new antineoplastic therapy, PFS was censored at the date of the last adequate tumor assessment before the earliest of the cut-off date or the start date of additional anti-neoplastic therapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria RECIST v1.1, as 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline and/or unequivocal progression of the non-target lesions and/or appearance of a new lesion. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm. (NCT01610284)
Timeframe: Date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to approximately 4 years

Intervention	Months (Median)
	FAS-Full population	FAS-Main cohort	FAS-PI3K pathway activated	FAS-PI3K pathway non-activated	FAS-PI3K pathway unknown
BKM120 100mg + Fulvestrant	6.9	6.8	6.8	6.9	8.7
Placebo + Fulvestrant	5.0	4.5	4.0	4.6	6.8

Number of Participants With Adverse Events of Grades 3 and 4 Severity

Participants with grades 3 and 4 severity adverse events were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03, unless otherwise specified. AEs are provided by System Organ Class (SOC). A patient with multiple adverse events within a primary system organ class was counted only once in the total row. (NCT02116803)
Timeframe: Until the last patient discontinued dovitinib up to 30 months

Intervention	Participants (Count of Participants)
	Any Primary system organ class	Blood and lymphatic system disorders	Cardiac disorders	Ear and Labyrinth disorders	Endocrine disorders	Eye disorders	Gastrointestinal disorders	General disorders & administration site conditions	Infections and Infestations	Injury, poisoning and procedural complications	Investigations	Metabolism and nutrition Disorders	Musculoskeletal and connective tissue disorders	Neoplasms benign, malignant & Unspecified	Nervous system Disorders	Psychiatric disorders	Respiratory, thoracic and mediastinal disorders	Skin and subcutaneous tissue disorders	Vascular disorders
Dovitinib	6	1	2	0	0	0	1	1	1	0	2	1	1	0	0	0	1	0	0
Dovitinib + Fulvestrant	2	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0

Article	Year
Comparative efficacy and safety of different combinations of three CDK4/6 inhibitors with endocrine therapies in HR+/HER-2 - metastatic or advanced breast cancer patients: a network meta-analysis. BMC cancer, Aug-31, Volume: 23, Issue: 1	2023
Palbociclib with Fulvestrant or Letrozole in Endocrine-Sensitive Patients with HR-Positive/HER2-Negative Advanced Breast Cancer: A Detailed Safety Analysis of the Randomized PARSIFAL Trial. The oncologist, 01-18, Volume: 28, Issue: 1	2023
VERONICA: Randomized Phase II Study of Fulvestrant and Venetoclax in ER-Positive Metastatic Breast Cancer Post-CDK4/6 Inhibitors - Efficacy, Safety, and Biomarker Results. Clinical cancer research : an official journal of the American Association for Cancer Research, 08-02, Volume: 28, Issue: 15	2022
The efficacy and safety of alpelisib in breast cancer: A real-world analysis. Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners, Volume: 28, Issue: 5	2022
[Patients treated with palbociclib and endocrine therapy for metastatic breast cancer: Can we predict the occurrence of severe early hematological toxicity?] Bulletin du cancer, Volume: 108, Issue: 5	2021
Real-world safety of palbociclib in breast cancer patients in the United States: a new user cohort study. BMC cancer, Jan-25, Volume: 21, Issue: 1	2021
Safety and efficacy of abemaciclib plus endocrine therapy in older patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: an age-specific subgroup analysis of MONARCH 2 and 3 trials. Breast cancer research and treatment, Volume: 186, Issue: 2	2021
Management of Abemaciclib-Associated Adverse Events in Patients with Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Safety Analysis of MONARCH 2 and MONARCH 3. The oncologist, Volume: 26, Issue: 1	2021
Abemaciclib: safety and effectiveness of a unique cyclin-dependent kinase inhibitor. Expert opinion on drug safety, Volume: 19, Issue: 8	2020
Time course and management of key adverse events during the randomized phase III SOLAR-1 study of PI3K inhibitor alpelisib plus fulvestrant in patients with HR-positive advanced breast cancer. Annals of oncology : official journal of the European Society for Medical Oncology, Volume: 31, Issue: 8	2020
Safety and efficacy of sirolimus combined with endocrine therapy in patients with advanced hormone receptor-positive breast cancer and the exploration of biomarkers. Breast (Edinburgh, Scotland), Volume: 52	2020
Efficacy and safety of palbociclib plus endocrine therapy in North American women with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. The breast journal, Volume: 26, Issue: 3	2020
Triggered Release Enhances the Cytotoxicity of Stable Colloidal Drug Aggregates. ACS chemical biology, 07-19, Volume: 14, Issue: 7	2019
Real-world clinical outcomes and toxicity in metastatic breast cancer patients treated with palbociclib and endocrine therapy. Breast cancer research and treatment, Volume: 176, Issue: 2	2019
The efficacy and safety of targeted therapy plus fulvestrant in postmenopausal women with hormone-receptor positive advanced breast cancer: A meta-analysis of randomized-control trials. PloS one, Volume: 13, Issue: 9	2018
Long-term Pooled Safety Analysis of Palbociclib in Combination With Endocrine Therapy for HR+/HER2- Advanced Breast Cancer. Journal of the National Cancer Institute, 04-01, Volume: 111, Issue: 4	2019
Efficacy and safety of fulvestrant in postmenopausal patients with hormone receptor-positive advanced breast cancer: a systematic literature review and meta-analysis. Breast cancer research and treatment, Volume: 171, Issue: 3	2018
Efficacy and safety in older patient subsets in studies of endocrine monotherapy versus combination therapy in patients with HR+/HER2- advanced breast cancer: a review. Breast cancer research and treatment, Volume: 167, Issue: 3	2018
Efficacy and safety of endocrine monotherapy as first-line treatment for hormone-sensitive advanced breast cancer: A network meta-analysis. Medicine, Volume: 96, Issue: 33	2017
Palbociclib in Combination With Fulvestrant in Women With Hormone Receptor-Positive/HER2-Negative Advanced Metastatic Breast Cancer: Detailed Safety Analysis From a Multicenter, Randomized, Placebo-Controlled, Phase III Study (PALOMA-3). The oncologist, Volume: 21, Issue: 10	2016
Targeting Estrogen Receptor Signaling with Fulvestrant Enhances Immune and Chemotherapy-Mediated Cytotoxicity of Human Lung Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research, Dec-15, Volume: 22, Issue: 24	2016
[Efficacy and Safety of the Selective Estrogen Receptor Down-Regulator "Fulvestrant" in Japanese Patients with Advanced, Recurrent, ER-Positive Postmenopausal Breast Cancer]. Gan to kagaku ryoho. Cancer & chemotherapy, Volume: 42, Issue: 7	2015
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps). PLoS computational biology, Volume: 7, Issue: 12	2011
Estrogen receptors and type 1 metabotropic glutamate receptors are interdependent in protecting cortical neurons against β-amyloid toxicity. Molecular pharmacology, Volume: 81, Issue: 1	2012
Effect of pollen from Typha angustata on hydrogen peroxide induced toxicity in osteoblastic MC3T3-E1 cells. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology, Volume: 41, Issue: 2	2012
Fulvestrant revisited: efficacy and safety of the 500-mg dose. Clinical breast cancer, Volume: 11, Issue: 4	2011
Emerging data on the efficacy and safety of fulvestrant, a unique antiestrogen therapy for advanced breast cancer. Expert opinion on drug safety, Volume: 10, Issue: 5	2011
Aroclor1254 interferes with estrogen receptor-mediated neuroprotection against beta-amyloid toxicity in cholinergic SN56 cells. Neurochemistry international, Volume: 59, Issue: 5	2011
Enhanced expression of ERalpha in astrocytes modifies the response of cortical neurons to beta-amyloid toxicity. Neurobiology of disease, Volume: 33, Issue: 3	2009
Neuroprotective effect of 17beta-estradiol against N-methyl-D-aspartate-induced retinal neurotoxicity via p-ERK induction. Journal of neuroscience research, Feb-01, Volume: 85, Issue: 2	2007
Neuroprotective effects of 17beta-estradiol and nonfeminizing estrogens against H2O2 toxicity in human neuroblastoma SK-N-SH cells. Molecular pharmacology, Volume: 70, Issue: 1	2006
Gonadal steroids differentially modulate neurotoxicity of HIV and cocaine: testosterone and ICI 182,780 sensitive mechanism. BMC neuroscience, Jun-08, Volume: 6	2005
Advances in endocrine therapy for breast cancer: considering efficacy, safety, and quality of life. Clinical journal of oncology nursing, Volume: 8, Issue: 6	2004
Deregulation of cell proliferation by polycyclic aromatic hydrocarbons in human breast carcinoma MCF-7 cells reflects both genotoxic and nongenotoxic events. Toxicological sciences : an official journal of the Society of Toxicology, Volume: 83, Issue: 2	2005
Synergistic effects of ICI 182,780 on the cytotoxicity of cisplatin in cervical carcinoma cell lines. Cancer chemotherapy and pharmacology, Volume: 53, Issue: 6	2004
17beta-estradiol protects oligodendrocytes from cytotoxicity induced cell death. Journal of neurochemistry, Volume: 89, Issue: 3	2004
An ICI 182,780-sensitive, membrane-related estrogen receptor contributes to estrogenic neuroprotective actions against amyloid-beta toxicity. Annals of the New York Academy of Sciences, Volume: 1007	2003
An oestrogen membrane receptor participates in estradiol actions for the prevention of amyloid-beta peptide1-40-induced toxicity in septal-derived cholinergic SN56 cells. Journal of neurochemistry, Volume: 85, Issue: 5	2003
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Article	Year
Novel class of 7-Oxabicyclo[2.2.1]heptene sulfonamides with long alkyl chains displaying improved estrogen receptor α degradation activity. European journal of medicinal chemistry, Nov-15, Volume: 182	2019
[Chronic administration of estrogen receptors antagonist reduces degree of hypoxia-induced pulmonary hypertension caused by chronic injections of estrogen in ovariectomised female Wistar rats]. Eksperimental'naia i klinicheskaia farmakologiia, Volume: 76, Issue: 7	2013
The effects of fulvestrant, an estrogen receptor antagonist, on the proliferation, differentiation and mineralization of osteoprecursor cells. Molecular medicine reports, Volume: 7, Issue: 2	2013
Prevention and treatment of cervical cancer in mice using estrogen receptor antagonists. Proceedings of the National Academy of Sciences of the United States of America, Nov-17, Volume: 106, Issue: 46	2009
Estradiol, tamoxifen and ICI 182,780 alter alpha3 and beta1 integrin expression and laminin-1 adhesion in oral squamous cell carcinoma cell cultures. Oral oncology, Volume: 44, Issue: 1	2008
Endocrine therapy--current benefits and limitations. Breast cancer research and treatment, Volume: 93 Suppl 1	2005
The estrogen receptor-alpha agonist 16alpha-LE2 inhibits cardiac hypertrophy and improves hemodynamic function in estrogen-deficient spontaneously hypertensive rats. Cardiovascular research, Sep-01, Volume: 67, Issue: 4	2005
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Article	Year
A Randomized, Open-label, Presurgical, Window-of-Opportunity Study Comparing the Pharmacodynamic Effects of the Novel Oral SERD AZD9496 with Fulvestrant in Patients with Newly Diagnosed ER Clinical cancer research : an official journal of the American Association for Cancer Research, 08-15, Volume: 26, Issue: 16	2020
Pharmacokinetic and pharmacodynamic analysis of fulvestrant in preclinical models of breast cancer to assess the importance of its estrogen receptor-α degrader activity in antitumor efficacy. Breast cancer research and treatment, Volume: 179, Issue: 1	2020
Fluoroestradiol positron emission tomography reveals differences in pharmacodynamics of aromatase inhibitors, tamoxifen, and fulvestrant in patients with metastatic breast cancer. Clinical cancer research : an official journal of the American Association for Cancer Research, Jul-15, Volume: 17, Issue: 14	2011
In silico prediction of volume of distribution in human using linear and nonlinear models on a 669 compound data set. Journal of medicinal chemistry, Jul-23, Volume: 52, Issue: 14	2009
Pharmacokinetic profile of the fulvestrant loading dose regimen in postmenopausal women with hormone receptor-positive advanced breast cancer. Clinical breast cancer, Volume: 8, Issue: 4	2008
Prenatal estrogen and progesterone deprivation impairs alveolar formation and fluid clearance in newborn piglets. Pediatric research, Volume: 60, Issue: 1	2006
Pharmacokinetic profile of intramuscular fulvestrant in advanced breast cancer. Clinical pharmacokinetics, Volume: 43, Issue: 8	2004
Fulvestrant: pharmacokinetics and pharmacology. British journal of cancer, Volume: 90 Suppl 1	2004
Equivalent single-dose pharmacokinetics of two different dosing methods of prolonged-release fulvestrant ('Faslodex') in postmenopausal women with advanced breast cancer. Cancer chemotherapy and pharmacology, Volume: 52, Issue: 4	2003
Pharmacokinetics of a single dose of fulvestrant prolonged-release intramuscular injection in postmenopausal women awaiting surgery for primary breast cancer. Clinical therapeutics, Volume: 25, Issue: 5	2003
Inhibition of volume-regulated anion channels in cultured endothelial cells by the anti-oestrogens clomiphene and nafoxidine. British journal of pharmacology, Volume: 132, Issue: 1	2001
Pharmacokinetics, pharmacological and anti-tumour effects of the specific anti-oestrogen ICI 182780 in women with advanced breast cancer. British journal of cancer, Volume: 74, Issue: 2	1996
The estrogen antagonist ICI 182,780 reduces cancellous bone volume in female rats. Endocrinology, Volume: 133, Issue: 6	1993
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Article	Year
SCR-6852, an oral and highly brain-penetrating estrogen receptor degrader (SERD), effectively shrinks tumors both in intracranial and subcutaneous ER + breast cancer models. Breast cancer research : BCR, 08-14, Volume: 25, Issue: 1	2023
Nanoparticle-Based Combination Therapy Enhances Fulvestrant Efficacy and Overcomes Tumor Resistance in ER-Positive Breast Cancer. Cancer research, 09-01, Volume: 83, Issue: 17	2023
Clinical Translation: Targeting the Estrogen Receptor. Advances in experimental medicine and biology, Volume: 1390	2022
Identification of estrogen receptor down-regulators for endocrine resistant breast cancer. The Journal of steroid biochemistry and molecular biology, Volume: 224	2022
Lapatinib- and fulvestrant-PAMAM dendrimer conjugates promote apoptosis in chemotherapy-induced senescent breast cancer cells with different receptor status. Biomaterials advances, Volume: 140	2022
Lasofoxifene as a potential treatment for therapy-resistant ER-positive metastatic breast cancer. Breast cancer research : BCR, 05-12, Volume: 23, Issue: 1	2021
Discovery of AZD9833, a Potent and Orally Bioavailable Selective Estrogen Receptor Degrader and Antagonist. Journal of medicinal chemistry, 12-10, Volume: 63, Issue: 23	2020
Discovery of GNE-149 as a Full Antagonist and Efficient Degrader of Estrogen Receptor alpha for ER+ Breast Cancer. ACS medicinal chemistry letters, Jun-11, Volume: 11, Issue: 6	2020
Design and Synthesis of Basic Selective Estrogen Receptor Degraders for Endocrine Therapy Resistant Breast Cancer. Journal of medicinal chemistry, 12-26, Volume: 62, Issue: 24	2019
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. Molecular pharmacology, Volume: 96, Issue: 5	2019
Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens. The Journal of biological chemistry, 11-15, Volume: 294, Issue: 46	2019
Antiestrogens in combination with immune checkpoint inhibitors in breast cancer immunotherapy. The Journal of steroid biochemistry and molecular biology, Volume: 193	2019
The oral selective oestrogen receptor degrader (SERD) AZD9496 is comparable to fulvestrant in antagonising ER and circumventing endocrine resistance. British journal of cancer, Volume: 120, Issue: 3	2019
Identification of an Orally Bioavailable Chromene-Based Selective Estrogen Receptor Degrader (SERD) That Demonstrates Robust Activity in a Model of Tamoxifen-Resistant Breast Cancer. Journal of medicinal chemistry, 09-13, Volume: 61, Issue: 17	2018
Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen Receptor Positive Breast Cancer. Journal of medicinal chemistry, 04-12, Volume: 61, Issue: 7	2018
Local delivery of hormonal therapy with silastic tubing for prevention and treatment of breast cancer. Scientific reports, 01-08, Volume: 8, Issue: 1	2018
Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ERα+ Breast Cancer. Journal of medicinal chemistry, 04-13, Volume: 60, Issue: 7	2017
Novel Selective Estrogen Receptor Downregulators (SERDs) Developed against Treatment-Resistant Breast Cancer. Journal of medicinal chemistry, 02-23, Volume: 60, Issue: 4	2017
The role of fulvestrant in endometrial cancer. Expert opinion on drug metabolism & toxicology, Volume: 13, Issue: 5	2017
Fulvestrant-3 Boronic Acid (ZB716): An Orally Bioavailable Selective Estrogen Receptor Downregulator (SERD). Journal of medicinal chemistry, 09-08, Volume: 59, Issue: 17	2016
Optimization of a Novel Binding Motif to (E)-3-(3,5-Difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic Acid (AZD9496), a Potent and Orally Bioavailable Selective Estrogen Receptor Downregu Journal of medicinal chemistry, Oct-22, Volume: 58, Issue: 20	2015
Identification of GDC-0810 (ARN-810), an Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts. Journal of medicinal chemistry, Jun-25, Volume: 58, Issue: 12	2015
Presence and bioavailability of bisphenol A in the uterus of rats and mice following single and repeated dietary administration at low doses. Reproductive toxicology (Elmsford, N.Y.), Volume: 49	2014
Role of fulvestrant in the management of postmenopausal breast cancer. Expert review of anticancer therapy, Volume: 11, Issue: 11	2011
The turnover of estrogen receptor α by the selective estrogen receptor degrader (SERD) fulvestrant is a saturable process that is not required for antagonist efficacy. Biochemical pharmacology, Jul-15, Volume: 82, Issue: 2	2011
HE3286: a novel synthetic steroid as an oral treatment for autoimmune disease. Annals of the New York Academy of Sciences, Volume: 1173	2009
Pharmacokinetics of a single dose of fulvestrant prolonged-release intramuscular injection in postmenopausal women awaiting surgery for primary breast cancer. Clinical therapeutics, Volume: 25, Issue: 5	2003
Insulin-like growth factor binding protein-3 induces apoptosis in MCF7 breast cancer cells. Biochemical and biophysical research communications, Aug-28, Volume: 237, Issue: 3	1997
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Article	Year
Mathematical Modeling Identifies Optimum Palbociclib-fulvestrant Dose Administration Schedules for the Treatment of Patients with Estrogen Receptor-positive Breast Cancer. Cancer research communications, Nov-16, Volume: 3, Issue: 11	2023
Phase 1b study of pan-AKT inhibitor vevorisertib alone or with paclitaxel or fulvestrant in PIK3CA/AKT/PTEN-mutated advanced solid tumors. Cancer, 06-15, Volume: 129, Issue: 12	2023
"The emerging role of capivasertib in breast cancer". Breast (Edinburgh, Scotland), Volume: 63	2022
The Impact of Real-World Alternative Dosing Strategies of Palbociclib on Progression-Free Survival in Patients with Metastatic Breast Cancer. Current oncology (Toronto, Ont.), 03-07, Volume: 29, Issue: 3	2022
Sapanisertib plus Fulvestrant in Postmenopausal Women with Estrogen Receptor-Positive/HER2-Negative Advanced Breast Cancer after Progression on Aromatase Inhibitor. Clinical cancer research : an official journal of the American Association for Cancer Research, 03-15, Volume: 28, Issue: 6	2022
The agonistic bioanalytical equivalent concentration: A novel tool for assessing the endocrine activity of environmental mixtures. Environmental toxicology and pharmacology, Volume: 89	2022
Latest generation estrogen receptor degraders for the treatment of hormone receptor-positive breast cancer. Expert opinion on investigational drugs, Volume: 31, Issue: 6	2022
ZEB2 regulates endocrine therapy sensitivity and metastasis in luminal a breast cancer cells through a non-canonical mechanism. Breast cancer research and treatment, Volume: 189, Issue: 1	2021
Phase Ib Study of Ribociclib plus Fulvestrant and Ribociclib plus Fulvestrant plus PI3K Inhibitor (Alpelisib or Buparlisib) for HR Clinical cancer research : an official journal of the American Association for Cancer Research, 01-15, Volume: 27, Issue: 2	2021
Fulvestrant for hormone-sensitive metastatic breast cancer. The Cochrane database of systematic reviews, 01-03, Volume: 1	2017
Patient database analysis of fulvestrant 500 mg in the treatment of metastatic breast cancer: A European perspective. Breast (Edinburgh, Scotland), Volume: 32	2017
Role of fulvestrant in the treatment of postmenopausal metastatic breast cancer patients. Expert review of clinical pharmacology, Volume: 9, Issue: 9	2016
Effective combination therapies in preclinical endocrine resistant breast cancer models harboring ER mutations. Oncotarget, Aug-23, Volume: 7, Issue: 34	2016
Heterogeneous estrogen receptor expression in circulating tumor cells suggests diverse mechanisms of fulvestrant resistance. Molecular oncology, Volume: 10, Issue: 7	2016
Pictilisib for oestrogen receptor-positive, aromatase inhibitor-resistant, advanced or metastatic breast cancer (FERGI): a randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet. Oncology, Volume: 17, Issue: 6	2016
A Phase I Trial of BKM120 (Buparlisib) in Combination with Fulvestrant in Postmenopausal Women with Estrogen Receptor-Positive Metastatic Breast Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research, Apr-01, Volume: 22, Issue: 7	2016
AZD2014, an Inhibitor of mTORC1 and mTORC2, Is Highly Effective in ER+ Breast Cancer When Administered Using Intermittent or Continuous Schedules. Molecular cancer therapeutics, Volume: 14, Issue: 11	2015
Aurora kinase B is important for antiestrogen resistant cell growth and a potential biomarker for tamoxifen resistant breast cancer. BMC cancer, Apr-08, Volume: 15	2015
Pharmacodynamic imaging guides dosing of a selective estrogen receptor degrader. Clinical cancer research : an official journal of the American Association for Cancer Research, Mar-15, Volume: 21, Issue: 6	2015
A good drug made better: the fulvestrant dose-response story. Clinical breast cancer, Volume: 14, Issue: 6	2014
Differences in the transcriptional response to fulvestrant and estrogen deprivation in ER-positive breast cancer. Clinical cancer research : an official journal of the American Association for Cancer Research, Aug-01, Volume: 20, Issue: 15	2014
Synthesis and biological evaluation of salpichrolide analogs as antiestrogenic agents. European journal of medicinal chemistry, Jul-23, Volume: 82	2014
Optimization of a validated stability-indicating RP-LC method for the determination of fulvestrant from polymeric based nanoparticle systems, drugs and biological samples. Biomedical chromatography : BMC, Volume: 28, Issue: 10	2014
The therapeutic role of fulvestrant in the management of patients with hormone receptor-positive breast cancer. Breast (Edinburgh, Scotland), Volume: 23, Issue: 3	2014
Estrogen improves the hyperdynamic circulation and hyporeactivity of mesenteric arteries by alleviating oxidative stress in partial portal vein ligated rats. World journal of gastroenterology, Oct-28, Volume: 19, Issue: 40	2013
Fulvestrant for advanced breast cancer: a meta-analysis. Cancer treatment reviews, Volume: 39, Issue: 7	2013
Role of fulvestrant in the management of postmenopausal breast cancer. Expert review of anticancer therapy, Volume: 11, Issue: 11	2011
[Effect of estrogen on mismatch repair gene expression in colon cancer cells]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology, Volume: 27, Issue: 7	2011
Emerging data on the efficacy and safety of fulvestrant, a unique antiestrogen therapy for advanced breast cancer. Expert opinion on drug safety, Volume: 10, Issue: 5	2011
17β-estradiol aggravates temporomandibular joint inflammation through the NF-κB pathway in ovariectomized rats. Arthritis and rheumatism, Volume: 63, Issue: 7	2011
Fulvestrant: a review of its use in the management of hormone receptor-positive metastatic breast cancer in postmenopausal women. Drugs, Feb-12, Volume: 71, Issue: 3	2011
Results of a phase II study comparing three dosing regimens of fulvestrant in postmenopausal women with advanced breast cancer (FINDER2). Breast cancer research and treatment, Volume: 123, Issue: 2	2010
Activation of G protein-coupled receptor 30 modulates hormone secretion and counteracts cytokine-induced apoptosis in pancreatic islets of female mice. Molecular and cellular endocrinology, May-14, Volume: 320, Issue: 1-2	2010
Pharmacokinetic profile of the fulvestrant loading dose regimen in postmenopausal women with hormone receptor-positive advanced breast cancer. Clinical breast cancer, Volume: 8, Issue: 4	2008
ICI 182,780 penetrates brain and hypothalamic tissue and has functional effects in the brain after systemic dosing. Endocrinology, Volume: 149, Issue: 10	2008
Effects of a phytoestrogen-containing soy extract on the growth-inhibitory activity of ICI 182 780 in an experimental model of estrogen-dependent breast cancer. Endocrine-related cancer, Volume: 14, Issue: 2	2007
Estrogenic agonist activity of ICI 182,780 (Faslodex) in hippocampal neurons: implications for basic science understanding of estrogen signaling and development of estrogen modulators with a dual therapeutic profile. The Journal of pharmacology and experimental therapeutics, Volume: 319, Issue: 3	2006
Newly discovered orally active pure antiestrogens. Bioorganic & medicinal chemistry letters, Sep-15, Volume: 16, Issue: 18	2006
Discovery of thiochroman derivatives bearing a carboxy-containing side chain as orally active pure antiestrogens. Bioorganic & medicinal chemistry letters, Aug-01, Volume: 16, Issue: 15	2006
Hemodynamic effects of acute and repeated exposure to raloxifene in ovariectomized sheep. American journal of physiology. Heart and circulatory physiology, Volume: 291, Issue: 3	2006
Investigation of central versus peripheral effects of estradiol in ovariectomized mice. The Journal of endocrinology, Volume: 187, Issue: 2	2005
Diffusion-time distribution analysis reveals characteristic ligand-dependent interaction patterns of nuclear receptors in living cells. Biochemistry, Sep-06, Volume: 44, Issue: 35	2005
Current and future perspectives on fulvestrant. Clinical breast cancer, Volume: 6 Suppl 1	2005
TAS-108, a novel oral steroidal antiestrogenic agent, is a pure antagonist on estrogen receptor alpha and a partial agonist on estrogen receptor beta with low uterotrophic effect. Clinical cancer research : an official journal of the American Association for Cancer Research, Jan-01, Volume: 11, Issue: 1	2005
Pharmacokinetic profile of intramuscular fulvestrant in advanced breast cancer. Clinical pharmacokinetics, Volume: 43, Issue: 8	2004
Equivalent single-dose pharmacokinetics of two different dosing methods of prolonged-release fulvestrant ('Faslodex') in postmenopausal women with advanced breast cancer. Cancer chemotherapy and pharmacology, Volume: 52, Issue: 4	2003
Pharmacokinetics of a single dose of fulvestrant prolonged-release intramuscular injection in postmenopausal women awaiting surgery for primary breast cancer. Clinical therapeutics, Volume: 25, Issue: 5	2003
A novel mechanism for endocrine-disrupting effects of polychlorinated biphenyls: direct effects on gonadotropin-releasing hormone neurones. Journal of neuroendocrinology, Volume: 14, Issue: 10	2002
Organochlorine pesticides directly regulate gonadotropin-releasing hormone gene expression and biosynthesis in the GT1-7 hypothalamic cell line. Molecular and cellular endocrinology, Jun-28, Volume: 192, Issue: 1-2	2002
[Developments of hormonal agents for breast cancer]. Gan to kagaku ryoho. Cancer & chemotherapy, Volume: 28, Issue: 7	2001
Is ICI 182,780 an antiprogestin in addition to being an antiestrogen? Breast cancer research and treatment, Volume: 60, Issue: 1	2000
Induction of the angiogenic factor VEGF in the uterus by the antiprogestin onapristone. Cancer letters, Aug-01, Volume: 156, Issue: 1	2000
Dehydroepiandrosterone stimulates the estrogen response element. The Journal of steroid biochemistry and molecular biology, Volume: 62, Issue: 5-6	1997
Discovery and synthesis of [6-hydroxy-3-[4-[2-(1-piperidinyl)ethoxy]phenoxy]-2-(4-hydroxyphenyl)]b enzo[b]thiophene: a novel, highly potent, selective estrogen receptor modulator. Journal of medicinal chemistry, May-09, Volume: 40, Issue: 10	1997
The estrogenic and antiestrogenic activities of phytochemicals with the human estrogen receptor expressed in yeast. Steroids, Volume: 62, Issue: 4	1997
Effects of short-term antiestrogen treatment of primary breast cancer on estrogen receptor mRNA and protein expression and on estrogen-regulated genes. Breast cancer research and treatment, Volume: 41, Issue: 1	1996
Pharmacokinetics, pharmacological and anti-tumour effects of the specific anti-oestrogen ICI 182780 in women with advanced breast cancer. British journal of cancer, Volume: 74, Issue: 2	1996
Differential effects of estrogen, tamoxifen and the pure antiestrogen ICI 182,780 in human drug-resistant leukemia cell lines. Cancer chemotherapy and pharmacology, Volume: 33, Issue: 2	1993
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Article	Year
ERβ1 Sensitizes and ERβ2 Desensitizes ERα-Positive Breast Cancer Cells to the Inhibitory Effects of Tamoxifen, Fulvestrant and Their Combination with All-Trans Retinoic Acid. International journal of molecular sciences, Feb-13, Volume: 24, Issue: 4	2023
Randomised, open-label, multicentric phase III trial to evaluate the safety and efficacy of palbociclib in combination with endocrine therapy, guided by ESR1 mutation monitoring in oestrogen receptor-positive, HER2-negative metastatic breast cancer patien BMJ open, Mar-03, Volume: 12, Issue: 3	2022
Lactic acidosis, a potential toxicity from drug-drug interaction related to concomitant ribociclib and metformin in preexisting renal insufficiency: A case report. Cancer reports (Hoboken, N.J.), Volume: 5, Issue: 8	2022
Cost Effectiveness of Ribociclib in Combination with Fulvestrant for the Treatment of Postmenopausal Women with HR+/HER2- Advanced Breast Cancer Who Have Received No or Only One Prior Line of Endocrine Therapy: A Canadian Healthcare Perspective. PharmacoEconomics, Volume: 39, Issue: 9	2021
Abemaciclib in combination with endocrine therapy for East Asian patients with HR+, HER2- advanced breast cancer: MONARCH 2 & 3 trials. Cancer science, Volume: 112, Issue: 6	2021
MDM2 inhibition in combination with endocrine therapy and CDK4/6 inhibition for the treatment of ER-positive breast cancer. Breast cancer research : BCR, 08-12, Volume: 22, Issue: 1	2020
A phase II feasibility study of palbociclib in combination with adjuvant endocrine therapy for hormone receptor-positive invasive breast carcinoma. Annals of oncology : official journal of the European Society for Medical Oncology, 09-01, Volume: 30, Issue: 9	2019
Antiestrogens in combination with immune checkpoint inhibitors in breast cancer immunotherapy. The Journal of steroid biochemistry and molecular biology, Volume: 193	2019
Effect of High-dose Vitamin C Combined With Anti-cancer Treatment on Breast Cancer Cells. Anticancer research, Volume: 39, Issue: 2	2019
Treatment patterns and clinical outcomes among patients receiving palbociclib in combination with an aromatase inhibitor or fulvestrant for HR+/HER2-negative advanced/metastatic breast cancer in real-world settings in the US: Results from the IRIS study. Breast (Edinburgh, Scotland), Volume: 43	2019
Long-term Pooled Safety Analysis of Palbociclib in Combination With Endocrine Therapy for HR+/HER2- Advanced Breast Cancer. Journal of the National Cancer Institute, 04-01, Volume: 111, Issue: 4	2019
Palbociclib Combined with Fulvestrant in Premenopausal Women with Advanced Breast Cancer and Prior Progression on Endocrine Therapy: PALOMA-3 Results. The oncologist, Volume: 22, Issue: 9	2017
Comparison of palbociclib in combination with letrozole or fulvestrant with endocrine therapies for advanced/metastatic breast cancer: network meta-analysis. Current medical research and opinion, Volume: 33, Issue: 8	2017
Phase II, randomized, placebo-controlled study of dovitinib in combination with fulvestrant in postmenopausal patients with HR Breast cancer research : BCR, 02-10, Volume: 19, Issue: 1	2017
FDA Approval of Palbociclib in Combination with Fulvestrant for the Treatment of Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research, Oct-15, Volume: 22, Issue: 20	2016
Palbociclib in Combination With Fulvestrant in Women With Hormone Receptor-Positive/HER2-Negative Advanced Metastatic Breast Cancer: Detailed Safety Analysis From a Multicenter, Randomized, Placebo-Controlled, Phase III Study (PALOMA-3). The oncologist, Volume: 21, Issue: 10	2016
A Phase I Study of the AKT Inhibitor MK-2206 in Combination with Hormonal Therapy in Postmenopausal Women with Estrogen Receptor-Positive Metastatic Breast Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research, 06-01, Volume: 22, Issue: 11	2016
A meta-analysis of anastrozole in combination with fulvestrant in the first line treatment of hormone receptor positive advanced breast cancer. Breast cancer research and treatment, Volume: 138, Issue: 3	2013
Phase II trial of exemestane in combination with fulvestrant in postmenopausal women with advanced, hormone-responsive breast cancer. Clinical breast cancer, Volume: 12, Issue: 2	2012
Effects of fulvestrant alone or combined with different steroids in human breast cancer cells in vitro. Climacteric : the journal of the International Menopause Society, Volume: 11, Issue: 4	2008
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

fulvestrant

Description

Cross-References

Synonyms (146)

Research Excerpts

Overview

Effects

Actions

Treatment

Roles (3)

Drug Classes (4)

Pathways (1)

Protein Targets (51)

Potency Measurements

Inhibition Measurements

Activation Measurements

Other Measurements

Biological Processes (337)

Molecular Functions (119)

Ceullar Components (63)

Bioassays (430)

Research

Studies (2,629)

Study Types

Clinical Trials (402)

Trial Overview

Trial Outcomes

Determination (All Subjects Treated (AST) Set): Safety and Toxicity by Assessment of the Frequency of Grade I-IV Haematological and Non-haematological Toxicities

Determination (for ITT (Intet-to-Treat Set): Efficacy of a Monthly Administration of Fulvestrant in Patients With Recurrent or Metastatic Endometrial Carcinoma by Assessment of the Clinical Tumour Response After 3 Injections of Fulvestrant

Determination (for ITT Set): Median Survival

Evaluation (Patient-reported): Change From Baseline in Health-related Quality of Life (HR-QoL) at 12 Months (12 Visits)

Time to Progression of Disease (TTP-Time To Progression, for ITT Set)

Clinical Benefit Rate

Objective Response Rate

Overall Survival

Time to Progression (Investigator Assessed)

Time to Progression

Time to Treatment Failure

Disease Control Rate (DCR)

Number of Participants Who Discontinue Study Treatment Due to an AE

Number of Participants Who Experience One or More Adverse Events (AEs)

Number of Participants With a Dose-Limiting Toxicity (DLT), for the Determination of Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)

Objective Response Rate (ORR)

Area Under the Curve From 0-24 Hours (AUC0-24 Hours) of Vevorisertib

Area Under the Curve From 0-24 Hours (AUC0-24 Hours) of Vevorisertib

Area Under the Curve From 0-24 Hours (AUC0-24 Hours) of Vevorisertib

Area Under the Curve From 0-24 Hours (AUC0-24 Hours) of Vevorisertib

Best Overall Response (BOR)

Elimination Half-life (t½) of Vevorisertib

Elimination Half-life (t½) of Vevorisertib

Elimination Half-life (t½) of Vevorisertib

Elimination Half-life (t½) of Vevorisertib

Elimination Half-life (t½) of Vevorisertib

Maximum Plasma Concentration (Cmax) of Vevorisertib

Maximum Plasma Concentration (Cmax) of Vevorisertib

Maximum Plasma Concentration (Cmax) of Vevorisertib

Clinical Response by RECIST Criteria of Estrogen Receptor Expression

Clinical Response by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Evaluated Every 8 Weeks

Number of Participants With Grade 3 or Greater Toxicity by Common Toxicity Criteria Version 3.0 That Were at Least Possibly Related to Study Drug.

Clinical Benefit Defined as Complete Response (CR), Partial Response (PR) or Stable Disease (SD) Lasting >= 24 Weeks, as Determined by the Investigator According to RECIST v1.1

Duration of Response (DOR)

Objective Response (OR)

Overall Survival (OS)

Percentage of Participants With Adverse Events (AEs)

Progression Free Survival (PFS)

Plasma Concentrations of Fulvestrant (in Absence of Venetoclax)

Plasma Concentrations of Fulvestrant (in Presence of Venetoclax)

Plasma Concentrations of Venetoclax

Phase 1b Dose Escalation: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) Through Day 28 at Each Dose Level of GS-5829

Phase 1b Dose Escalation: PK Parameter: AUCtau of GS-5829

Phase 1b Dose Escalation: Pharmacokinetic (PK) Parameter: Cmax of GS-5829

Phase I: Disease Control Rate (DCR)

Phase I: Duration of Response (DoR)

Phase I: Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment

Phase I: Number of Participants With Dose Limiting Toxicities (DLTs)

Phase I: Objective Response Rate-Investigator Assessment

Phase I: Progression-free Survival (PFS)

Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays Until End of the Study

Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays

Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study