gestodene and Breast-Neoplasms

gestodene has been researched along with Breast-Neoplasms* in 10 studies

Reviews

1 review(s) available for gestodene and Breast-Neoplasms

ArticleYear
Progestins in preventive hormone therapy. Including pharmacology of the new progestins, desogestrel, norgestimate, and gestodene: are there advantages?
    Obstetrics and gynecology clinics of North America, 1994, Volume: 21, Issue:2

    Progestins have played an important role in hormone replacement therapy (HRT). This article reviews the history, structure, and pharmacology of synthetic progestins, including the new progestins, norgestimate, gestodene, and desogestrel. The benefits and potential effect on carcinoma of the breast for each HRT are summarized. Current treatment alternatives are addressed.

    Topics: Breast Neoplasms; Cardiovascular Diseases; Desogestrel; Endometrium; Estrogen Replacement Therapy; Female; Humans; Norgestrel; Norpregnenes; Osteoporosis, Postmenopausal; Progesterone Congeners; Risk Factors; Structure-Activity Relationship

1994

Other Studies

9 other study(ies) available for gestodene and Breast-Neoplasms

ArticleYear
Combined Hormonal Contraceptive Use and Risk of Breast Cancer in a Population of Women With a Family History.
    Clinical breast cancer, 2018, Volume: 18, Issue:1

    We estimated the association between combined hormonal contraceptive (CHC) use and breast cancer (BC) incidence in a well-selected population of women at familial risk of BC at the Modena Family Cancer Clinic.. We performed a retrospective cohort study by reviewing the data from 2527 women (4.5% BRCA mutation carriers, 72.2% high risk, and 23.3% intermediate risk using the Modena criteria and the Tyrer-Cuzick model).. We did not find any specific feature of breast cancer (infiltration, hormone receptor and HER2 status, onset before age 35 years, multiple diagnoses) in the CHC users (P > .05). Only 2.0% of women used a preparation with ≥ 50 μg of ethinylestradiol (EE). The use of CHCs was not associated with an increased risk of breast cancer (cumulative hazard: never used, 0.17; CHC users, 0.20; P = .998), regardless of the duration of use (cumulative hazard: never used, 0.17, used < 5 years, 0.20; used 5-10 years, 0.14; used > 10 years, 0.25; P = .414). This was confirmed for the different risk groups when interacted in a Cox proportional hazard regression model. The EE dose did not influence the risk of BC (cumulative hazard, 2.37; 95% confidence interval, 0.53-10.1; never used, 0.18; EE < 20 μg used, 0.04; EE ≥ 20 μg used, 0.16; P = .259). The types of progestins used might influence the risk, with some, such as gestodene (P = .028) and cyproterone acetate (P = .031), associated with an even greater reduced risk.. CHC use does not increase the risk of BC in a population of women with a family history, encouraging CHC use in this group of women.

    Topics: Adult; Age of Onset; Aged; Aged, 80 and over; Breast Neoplasms; Contraceptive Agents; Cyproterone Acetate; Ethinyl Estradiol; Female; Humans; Incidence; Medical History Taking; Middle Aged; Norpregnenes; Retrospective Studies; Risk Factors; Young Adult

2018
Effects of two classes of progestagens, pregnane and 19-nortestosterone derivatives, on cell growth of human breast tumor cells: I. MCF-7 cell lines.
    The Journal of steroid biochemistry and molecular biology, 1995, Volume: 55, Issue:3-4

    The effects of two classes of progestagens, e.g. pregnane [Org 2058, medroxyprogesterone acetate (MPA), R5020, progesterone (PROG)] and 19-nortestosterone derived progestagens [3-ketodesogestrel (KDG), levonorgestrel (LNG), gestodene (GES), norethisterone (NE), Org 30659] on proliferation of three estradiol (E2)-dependent human breast tumor MCF-7 cell lines of different origin [Van der Burg (B), Litton bionetics (L) and McGrath (M)] were studied. The pregnane derivatives hardly stimulated cell growth at 10(-6) M in MCF-7 B and L cells except for Org 2058 in B cells, whereas in M cells a statistically significant growth induction was observed except for PROG. The 19-nortestosterone derivatives induced cell growth at doses at 10(-7) M or higher in all three cell lines. NE, GES and Org 30659 were more potent stimulators than KDG and LNG at 10(-7) M. E2 already showed maximal stimulation at 10(-10) M. For all three cell lines, the effects and ranking of the individual progestagens were similar. Antiprogestagens, like RU 38486 and Org 31710 could not block these stimulatory effects while antiestrogens like 4-hydroxytamoxifen and ICI 164,384 could. This suggests that cell growth by the above-mentioned progestagens occurs via an interaction with the estrogen receptor. Indeed, displacement studies with cytosol from MCF-7 M cells revealed that at very high concentrations NE, GES and Org 30659 were able to displace 50% of the radiolabelled E2, while KDG and LNG could not. Relative binding affinities (RBAs) were 0.010, 0.025 and 0.015% for NE, GES and Org 30659, respectively. The effect of the two classes of progestagens on cell proliferation was also investigated at several dose levels in combination with E2 (10(-10) M) in the MCF-7 B cell line. This resulted in a statistically significant inhibition of cell growth with R5020, MPA and most of the 19-nortestosterone derivatives at concentrations of 10(-8) M. Org 2058 and NE did not have any influence on E2-induced growth. The inhibitory effects could not be blocked by antiprogestagens. In summary these studies with 3 subclones of MCF-7 cells show that the pregnane derived progestagens stimulate growth only in one subclone, whereas the 19-nortestosterone derived progestagens do so in all three subclones. The progestagens possess estrogenic activity only at high pharmacological doses, being 10,000 times weaker than estradiol. In combination with estrogens most progestagens gave a reduction of E2-stimulated growth in t

    Topics: Adenocarcinoma; Breast Neoplasms; Cell Division; Desogestrel; Estradiol; Estrogen Antagonists; Female; Humans; Levonorgestrel; Medroxyprogesterone Acetate; Models, Statistical; Nandrolone; Norethindrone; Norpregnenes; Pregnanes; Pregnenediones; Progesterone; Promegestone; Receptors, Androgen; Receptors, Estrogen; Receptors, Progesterone; Tumor Cells, Cultured

1995
Effects of two classes of progestagens, pregnane and 19-nortestosterone derivatives, on cell growth of human breast tumor cells: II. T47D cell lines.
    The Journal of steroid biochemistry and molecular biology, 1995, Volume: 55, Issue:3-4

    Two classes of progestagens, e.g. pregnane [Org 2058, progesterone (PROG), R5020, medroxyprogesterone acetate (MPA)] and 19-nortestosterone derived progestagens [norethisterone (NE), levonorgestrel (LNG), 3-ketodesogestrel (KDG), gestodene (GES), Org 30659] were studied for their effect on cell growth of two human breast tumor T47D cell lines of different origin, i.e. from ATCC (A) and Sutherland (S) et al. [Sutherland et al., Cancer Res. 48 (1988) 5084-5091]. The effect of estradiol (E2) and progestagens alone as well as the combined effect of E2 (10(-10) M) and progestagens were investigated at several dose levels. Compared with E2-induced growth at 10(-10) M, pregnane and 19-nortestosterone derived progestagens at 10(-6) M alone did enhance cell growth in T47D-A cells up to 25 and 100% respectively, whereas in T47D-S cells they did not influence growth. All these progestagens at 10(-6) M did not affect E2-induced growth in T47D-A cells, whereas in T47D-S cells they completely reduced cell proliferation at doses between 10(-10) and 10(-8) M. The involvement of progestagen (PR) and estrogen (ER) receptors with respect to growth stimulation was studied by using specific antihormones. In T47D-A cells, the antiprogestagens RU 38486 and Org 31710 could not block progestagen-induced growth. Antiestrogens, like 4-hydroxytamoxifen and ICI 164,384, inhibited the 19-nortestosterone derivative-induced cell growth by approx. 50%. Remarkably, both antiprogestagens alone could also inhibit E2-induced growth in T47D-A cells by about 50%. In T47D-S cells, E2-induced cell growth was completely blocked by both antiprogestagens and antiestrogens. Both antiprogestagens in T47D-S cells were equipotent to 4-hydroxytamoxifen and 10-fold more potent than ICI 164,384. In conclusion pregnane and 19-nortestosterone-derived progestagens stimulated cell growth in T47D-A cells at high unphysiological concentrations, whereas they did not affect cell growth in T47D-S cells. The 19-nortestosterone derivative induced growth in T47D-A cells could partially be inhibited by antiestrogens. In T47D-A cells, E2-induced cell growth was not influenced by both classes of progestagens, whereas in T47D-S cells all tested progestagens, antiprogestagens, and antiestrogens inhibited E2-induced cell growth completely. These results with T47D cells as well as those obtained previously with MCF-7 cells show that subclones of cell lines may respond differently to various types of progestagens in the pres

    Topics: Breast Neoplasms; Carcinoma; Cell Division; Desogestrel; Dose-Response Relationship, Drug; Estradiol; Estrenes; Estrogen Antagonists; Female; Furans; Humans; Levonorgestrel; Medroxyprogesterone Acetate; Mifepristone; Nandrolone; Norethindrone; Norpregnenes; Pregnanes; Pregnenediones; Progesterone; Promegestone; Tumor Cells, Cultured

1995
[Chemoprevention: a new strategy in the fight against breast cancer?].
    Bulletin de la Societe des sciences medicales du Grand-Duche de Luxembourg, 1993, Volume: 130, Issue:1

    Topics: Adult; Aged; Breast Neoplasms; Contraceptives, Oral; Female; Humans; Middle Aged; Norpregnenes; Primary Prevention; Progesterone Congeners; Retinoids; Risk Factors; Tamoxifen

1993
Norgestrel and gestodene stimulate breast cancer cell growth through an oestrogen receptor mediated mechanism.
    British journal of cancer, 1993, Volume: 67, Issue:5

    There is great concern over the long-term influence of oral contraceptives on the development of breast cancer in women. Oestrogens are known to stimulate the growth of human breast cancer cells, and this laboratory has previously reported (Jeng & Jordan, 1991) that the 19-norprogestin norethindrone could stimulate the proliferation of MCF-7 human breast cancer cells. We studied the influence of the 19-norprogestins norgestrel and gestodene compared to a 'non' 19-norprogestin medroxyprogesterone acetate (MPA) on MCF-7 cell proliferation. The 19-norprogestins stimulated proliferation at a concentration of 10(-8) M, while MPA could not stimulate proliferation at concentrations as great as 3 x 10(-6) M. The stimulatory activity of the 19-norprogestins could be blocked by the antioestrogen ICI 164,384, but not by the antiprogestin RU486. Transfection studies with the reporter plasmids containing an oestrogen response element or progesterone response element (vitERE-CAT, pS2ERE-CAT, and PRE15-CAT) were performed to determine the intracellular action of norgestrel and gestodene. The 19-norprogestins stimulated the vitERE-CAT activity maximally at 10(-6) M, and this stimulation was inhibited by the addition of ICI 164,384. MPA did not stimulate vitERE-CAT activity. A single base pair alteration in the palindromic sequence of vitERE (resulting in the pS2ERE) led to a dramatic decrease in CAT expression by the 19-norprogestins, suggesting that the progestin activity required specific response element base sequencing. PRE15-CAT activity was stimulated by norgestrel, gestodene and MPA at concentrations well below growth stimulatory activity. This stimulation could be blocked by RU486. These studies suggest that the 19-norprogestins norgestrel and gestodene stimulate MCF-7 breast cancer cell growth by activating the oestrogen receptor.

    Topics: Base Sequence; Breast Neoplasms; Cell Division; Estradiol; Estrogens; Female; Gene Expression; Humans; In Vitro Techniques; Mifepristone; Molecular Sequence Data; Norgestrel; Norpregnenes; Polyunsaturated Alkamides; Promoter Regions, Genetic; Receptors, Estrogen; Regulatory Sequences, Nucleic Acid; Transcription, Genetic; Tumor Cells, Cultured

1993
Effects of progestins on the proliferation of estrogen-dependent human breast cancer cells under growth factor-defined conditions.
    The Journal of steroid biochemistry and molecular biology, 1992, Volume: 42, Issue:5

    The effect was studied of four different synthetic progestins (Org 30659, gestodene, 3-ketodesogestrel and levonorgestrel) on the proliferation of the 17 beta estradiol (E2)-dependent human breast cancer cell line MCF7. All progestins were found to stimulate proliferation, but only at high pharmacological dosages. Moreover, like estrogens the progestins at high concentrations synergistically stimulated MCF7 cell proliferation together with low concentrations of insulin. This stimulatory effect could be blocked by antiestrogens, but not by antiglucocorticoids and antiprogestins. This suggests that growth stimulation by these progestins (or their metabolites) occurs through crossreaction with the E2 receptor (ER). This is confirmed by the observation that the strong synthetic progestin Org 2058 does not stimulate proliferation. The absence of a progesterone receptor (PR)-mediated growth response seems not to be due to aberrant PR expression in these cells; 27,000 receptors (Kd 1.7 x 10(-10)M) per cell were present under growth-assay conditions. Growth stimulation by E2 in the absence or presence of insulin, is slightly inhibited or unaffected by the progestins, respectively. Our data do not support a role for the recently identified gestodene binding sites [Colletta et al., J. Steroid Biochem. 33 (1989) 1055-1061] in mediating gestodene effects on breast cancer cells: gestodene and 3-ketodesogestrel, a compound that does not bind to these gestodene binding sites, showed a similar biological activity. The effects of the progestins on the MCF7 breast cancer cell line, indicate that the use of these compounds at very high concentrations may be unfavourable, but do not support a role for them in directly stimulating breast tumor proliferation at the low progestin concentration which are reached in the serum in oral contraceptive users.

    Topics: Analysis of Variance; Breast Neoplasms; Cell Division; Contraceptives, Oral; DNA; Estrogens; Growth Substances; Humans; Insulin; Norpregnenes; Progestins; Tumor Cells, Cultured

1992
The growth inhibition of human breast cancer cells by a novel synthetic progestin involves the induction of transforming growth factor beta.
    The Journal of clinical investigation, 1991, Volume: 87, Issue:1

    Recent experimental work has identified a novel intracellular binding site for the synthetic progestin, Gestodene, that appears to be uniquely expressed in human breast cancer cells. Gestodene is shown here to inhibit the growth of human breast cancer cells in a dose-dependent fashion, but has no effect on endocrine-responsive human endometrial cancer cells. Gestodene induced a 90-fold increase in the secretion of transforming growth factor-beta (TGF-beta) by T47D human breast cancer cells. Other synthetic progestins had no effect, indicating that this induction is mediated by the novel Gestodene binding site and not by the conventional progesterone receptor. Furthermore, in four breast cancer cell lines, the extent of induction of TGF-beta correlated with intracellular levels of Gestodene binding site. No induction of TGF-beta was observed with the endometrial cancer line, HECl-B, which lacks the Gestodene binding site, but which expresses high levels of progesterone receptor. The inhibition of growth of T47D cells by Gestodene is partly reversible by a polyclonal antiserum to TGF-beta. These data indicate that the growth-inhibitory action of Gestodene may be mediated in part by an autocrine induction of TGF-beta.

    Topics: Binding Sites; Breast Neoplasms; Cell Division; Enzyme-Linked Immunosorbent Assay; Estrogen Antagonists; Female; Humans; Norpregnenes; Progesterone Congeners; Radioligand Assay; Receptors, Progesterone; RNA, Messenger; Transforming Growth Factor beta; Tumor Cells, Cultured

1991
Lack of binding of gestodene to estrogen receptor in human breast cancer tissue.
    European journal of cancer (Oxford, England : 1990), 1990, Volume: 26, Issue:5

    Competition studies with progesterone and estradiol receptors of human myometrial tissue as well as of mammary cancer tissue showed that gestodene bound with high affinity to the progesterone receptor, as did other synthetic and natural progestogens. However, gestodene did not bind to the estradiol receptor. The relative binding affinities of all tested synthetic and natural ligands showed no organ-specific differences and no differences between neoplastically transformed and normal tissues.

    Topics: Binding, Competitive; Breast Neoplasms; Female; Humans; In Vitro Techniques; Myometrium; Norpregnenes; Progesterone Congeners; Promegestone; Receptors, Estrogen; Receptors, Progesterone

1990
Differences in oestrogen receptors in malignant and normal breast tissue as identified by the binding of a new synthetic progestogen.
    British journal of cancer, 1986, Volume: 54, Issue:3

    Oestrogen receptor protein (ER) was detected in 9 of 11 samples of malignant breast tissue and 8 of 9 samples of normal breast tissue. Levels of cytosolic ER (ERc) in malignant breast were 21-1102 fmol mg-1 soluble protein (Kd 1.8 X 10(-9)-3.1 X 10(-8) mol l-1) and those of nucleosolic ER (ERn), 13-526 fmol mg-1 soluble protein (Kd 2.1 X 10(-9)-1.4 X 10(-8) mol l-1). In normal breast tissue ERc levels were 33-640 fmol mg-1 soluble protein (Kd 1.3 X 10(-10)-3.2 X 10(-9) mol l-1), ERn was detected in only 2 samples, 8 and 87 fmol mg-1 soluble protein with Kd 3.2 X 10(-9) and 1.4 X 10(-9) l mol-1 respectively. 17 alpha-ethinyl-13 beta-ethyl-17 beta-hydroxy-4,15-gonadiene-3-one (gestodene), a new synthetic progestogen displaced 3H-oestradiol (3H-E2) from both ERc and ERn in malignant tissue but not in normal breast, or these receptors from endometrial tissue. In competition studies gestodene was approximately 3 times more effective in displacing 3H-E2 from ERc and ERn in malignant breast tissue than the natural ligand. Quantitation of ER by gestodene were ERc, 12-1134 fmol gestodene bound mg-1 soluble protein (Kd 1 X 10(-9)-8.1 X 10(-9) mol l-1); ERn, 17-531 fmol gestodene bound mg-1 soluble protein (Kd 1.6 X 10(-9)-1.1 X 10(-8) mol l-1). L-13-ethyl-17 alpha-ethinyl, 17 beta-hydroxy-gonen-3-one (levonorgestrel) showed no binding to ER in malignant breast, normal breast or endometrial tissue. In circulation both gestodene and levonorgestrel displaced E2 from sex hormone binding globulin more than any of the androgens tested. These results suggest that gestodene is a progestogen with oestrogenic and/or antioestrogenic properties and provide strong evidence for differences in ER from malignant and normal breast tissue.

    Topics: Binding, Competitive; Breast Diseases; Breast Neoplasms; Cytosol; Female; Humans; Norpregnenes; Receptors, Estrogen; Sex Hormone-Binding Globulin; Transcortin

1986