ospemifene and Breast-Neoplasms

ospemifene has been researched along with Breast-Neoplasms* in 14 studies

Reviews

6 review(s) available for ospemifene and Breast-Neoplasms

ArticleYear
Safety and Serum Estradiol Levels in Hormonal Treatments for Vulvovaginal Atrophy in Breast Cancer Survivors: A Systematic Review and Meta-Analysis.
    Clinical breast cancer, 2023, Volume: 23, Issue:8

    Vulvo-vaginal atrophy (VVA) or genitourinary syndrome of menopause (GSM) is a common condition among breast cancer (BC) patients, especially those undergoing antiestrogen therapy. Despite being an option in refractory cases, the safety of hormonal treatment remains uncertain in this population. The aim of this study was to review the safety and serum estrogen levels of hormonal therapy in patients with BC history presenting with VVA symptoms. Pubmed, Embase, and Cochrane were searched for studies comparing different hormonal treatment options for VVA in breast cancer survivors. Statistical analysis was performed using a random effects model and heterogeneity using Cochran's Q-statistic and the I2 index. We included 17 studies, of which 5 were randomized controlled trials (RCTs). Treatment modalities included in this study were topical vaginal estradiol and estriol preparations, vaginally applied testosterone, DHEA, and ospemifene. We found that, among patients treated with the estriol and estradiol preparations, there was an average increase of 7.67 pg/mL (SMD 7.67 pg/mL; 95% CI -1.00, 16.35; p < .001). Analysis of the testosterone group found temporary peaks of serum estradiol levels, but 1 study showed persistent elevation above normal postmenopausal levels. One study with prasterone revealed no elevation of serum estradiol concentration. One study with ospemifene demonstrated no increase in the risk of BC recurrence. In conclusion, among treatments available for BC survivors, low-dose vaginal estrogen showed the smallest changes in serum estradiol levels and had the most evidence, but safety remains unclear, especially for patients on aromatase inhibitors. Alternative treatments such as ospemifene need more data supporting safety and efficacy. These results suggest that concerns related to cancer recurrence should keep aiming for the lowest possible concentration.

    Topics: Atrophy; Breast Neoplasms; Cancer Survivors; Estradiol; Estriol; Estrogens; Female; Humans; Neoplasm Recurrence, Local; Survivors; Testosterone; Vagina; Vaginal Diseases

2023
Vaginal estrogen and mammogram results: case series and review of literature on treatment of genitourinary syndrome of menopause (GSM) in breast cancer survivors.
    Menopause (New York, N.Y.), 2018, Volume: 25, Issue:7

    To examine mammographic density before and after at least 1 year of vaginal estrogen use in a small cohort of healthy postmenopausal women and women with a personal history of breast cancer.. We extracted data via chart review of patients from a single practitioner's menopause specialty clinic in Baltimore, MD. Mammographic change was primarily determined via the Bi-RADS scoring system, including the Bi-RADS density score. In addition, we conduct a narrative review of the current literature on the usage of local estrogen therapy, and systemic and local alternatives in the treatment of genitourinary syndrome of menopause (GSM) in breast cancer survivors.. Twenty healthy postmenopausal women and three breast cancer survivors fit our inclusion criteria. Amongst these two groups, we did not find an increase in mammographic density after at least 1 year and up to 18 years of local vaginal estrogen. Ospemifene use in one patient did not appear to be associated with any change in Bi-RADS score. Our narrative review found little data on the effects of vaginal estrogen therapy or newer alternative systemic therapies such as ospemifene on mammographic density.. Low-dose vaginal estrogen use for 1 or more years in a small cohort of women with GSM did not appear to be associated with any changes in breast density or Bi-RADS breast cancer risk scores in the majority of study participants, including three breast cancer survivors. Larger long-term controlled clinical trials should be conducted to examine the effects of low-dose vaginal estrogen on mammographic density in women with and without a personal history of breast cancer. Furthermore, relative efficacy and risk of vaginal estrogen compared with other forms of treatment for GSM should also be studied in long-term trials.

    Topics: Administration, Intravaginal; Adult; Aged; Breast; Breast Neoplasms; Cancer Survivors; Estrogens; Female; Female Urogenital Diseases; Humans; Mammography; Middle Aged; Postmenopause; Retrospective Studies; Syndrome; Tamoxifen; Treatment Outcome

2018
Local hormone therapy for genitourinary syndrome of menopause in breast cancer patients: is it safe?
    Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 2017, Volume: 33, Issue:6

    The genitourinary syndrome of menopause (GSM) is a frequent complaint among breast cancer (BC) survivors that lead to an important affection of their quality of life (QoL). Lifestyle measures such as smoking cessation or regular sexual activity are usually insufficient to significantly improve GMS and although therapies such as lubricants and polycarbophil moisturized gels are considered first-line therapies to alleviate symptoms of vulvovaginal atrophy, these non-hormonal options are not able to reverse atrophy once it occurs. Instead, this complaint is corrected by local estrogens. The estrogen vaginal treatment usually used to treat GSM, is an issue of concern in this group due to the possible negative effect over the BC outcomes. On the other hand, the worsening of QoL in these patients due to symptoms related to GSM can lead to discontinuation of hormone adjuvant therapies and therefore must be addressed properly. The goal of this review is to contribute to health care professionals to make an informed decision to care for their BC patients.

    Topics: Administration, Intravaginal; Antineoplastic Agents; Breast Neoplasms; Estradiol; Estrogens; Female; Female Urogenital Diseases; Humans; Menopause, Premature; Tamoxifen

2017
Selective estrogen receptor modulators and the combination therapy conjugated estrogens/bazedoxifene: A review of effects on the breast.
    Post reproductive health, 2015, Volume: 21, Issue:3

    Traditional menopausal hormone therapy containing estrogens/progestin has been associated with an increased risk of breast cancer, and estrogen exposure is known to promote growth and proliferation of a majority of breast cancers. Therefore, it is important for clinicians to consider the breast safety profile of any hormone-based therapy used in postmenopausal women. This review provides an overview of the breast safety and tolerability profiles of currently marketed selective estrogen receptor modulators, antiestrogens, and the first tissue selective estrogen complex combining conjugated estrogens with the selective estrogen receptor modulator bazedoxifene in postmenopausal women. Selective estrogen receptor modulators and antiestrogens act as estrogen receptor antagonists in the breast. Tamoxifen, toremifene, and the selective estrogen receptor degrader fulvestrant are used to treat breast cancer, and tamoxifen and raloxifene protect against breast cancer in high-risk women. Postmenopausal women using selective estrogen receptor modulators for prevention or treatment of osteoporosis (raloxifene, bazedoxifene) can be reassured that these hormonal treatments do not adversely affect their risk of breast cancer and may, in the case of raloxifene, even be protective. There are limited data on breast cancer in women who use ospemifene for dyspareunia. Conjugated estrogens/bazedoxifene use for up to two years did not increase mammographic breast density or breast pain/tenderness, and there was no evidence of an increased risk of breast cancer, suggesting that conjugated estrogens/bazedoxifene has an improved breast safety profile compared with traditional menopausal hormone therapies. Future research will continue to focus on development of selective estrogen receptor modulators and selective estrogen receptor modulator combinations capable of achieving the ideal balance of estrogen receptor agonist and antagonist effects.

    Topics: Animals; Breast; Breast Neoplasms; Drug Therapy, Combination; Estradiol; Estrogen Antagonists; Estrogens; Estrogens, Conjugated (USP); Female; Fulvestrant; Humans; Indoles; Osteoporosis; Postmenopause; Protective Factors; Raloxifene Hydrochloride; Risk Assessment; Selective Estrogen Receptor Modulators; Tamoxifen; Toremifene

2015
Use of SERMs for treatment in postmenopausal women.
    The Journal of steroid biochemistry and molecular biology, 2014, Volume: 142

    Selective estrogen receptor modulators (SERMs) are synthetic non-steroidal agents which have varying estrogen agonist and antagonist activities in different tissues, most likely due to the receptor conformation changes associated with that SERM's binding and the subsequent effect on transcription. Clinical trials aim to differentiate amongst SERMs on selected target tissues for use in postmenopausal women including effects on breast, bone, cardiovascular venous thrombosis risk, endometrium, vagina, vasomotor symptoms, and brain. This paper describes differences in clinical effects on selected target tissues of SERMs that are approved, discontinued or in development. FDA approved SERMs include tamoxifen and toremifene used for prevention and treatment of breast cancer, raloxifene approved for prevention and treatment of osteoporosis and prevention of invasive breast cancer, and ospemifene approved for treatment of dyspareunia from menopausal vaginal atrophy. The FDA approved first tissue selective estrogen complex (TSEC) a pairing of conjugated equine estrogens with the SERM, bazedoxifene. This pairing reduces the risk of endometrial hyperplasia that can occur with the estrogenic component of the TSEC without the need for a progestogen in women with a uterus. It also allows for the estrogenic benefits on relief of hot flashes and prevention of bone loss without stimulating the breast or the endometrium. In clinical practice, the tissue-selective actions of SERMs, alone or paired with estrogens, allow for individualization in meeting the treatment needs of postmenopausal women by providing targeted tissue effects. This article is part of a Special Issue entitled 'Menopause'.

    Topics: Breast Neoplasms; Clinical Trials as Topic; Dyspareunia; Estrogens, Conjugated (USP); Female; Hot Flashes; Humans; Indoles; Osteoporosis; Osteoporosis, Postmenopausal; Postmenopause; Pyrrolidines; Raloxifene Hydrochloride; Receptors, Estrogen; Selective Estrogen Receptor Modulators; Tamoxifen; Tetrahydronaphthalenes; Toremifene

2014
Ospemifene, vulvovaginal atrophy, and breast cancer.
    Maturitas, 2013, Volume: 74, Issue:3

    The incidence and severity of vulvovaginal atrophy (VVA) in postmenopausal breast cancer patients has a significant impact on quality of life. While the etiology of VVA is primarily related to low estrogen levels seen in menopause, women with breast cancer have an added risk of VVA induced by a combination of chemotherapy, hormonal therapy, and menopause. Ospemifene is a new, non-hormonal selective estrogen receptor modulator (SERM) triphenylethylene derivative that is effective in treating VVA in postmenopausal women. Although other SERMs have antagonistic effects on the vagina, ospemifene exerts an estrogen-like effect on the vaginal epithelium. This review will focus on data demonstrating the antiestrogenic activity of ospemifene in several unique breast cancer animal models, and the implications for utilizing ospemifene in patients with breast cancer suffering from VVA. Additional research addressing the expanded use of ospemifene in breast cancer patients is also warranted.

    Topics: Animals; Antineoplastic Agents, Hormonal; Atrophy; Breast Neoplasms; Disease Models, Animal; Female; Humans; Menopause; Postmenopause; Quality of Life; Selective Estrogen Receptor Modulators; Tamoxifen; Vagina; Vulva

2013

Other Studies

8 other study(ies) available for ospemifene and Breast-Neoplasms

ArticleYear
No increase in incidence or risk of recurrence of breast cancer in ospemifene-treated patients with vulvovaginal atrophy (VVA).
    Maturitas, 2020, Volume: 142

    To estimate the incidence and recurrence of breast cancer (BC) in patients with vulvovaginal atrophy (VVA) treated with ospemifene and matched untreated VVA patients using real-world data.. Retrospective matched cohort study.. VVA patients were identified from the 2011-2018 US MarketScan® insurance claims database. For incidence, ospemifene-treated VVA patients without evidence of BC prior to index treatment were matched to two untreated VVA controls similarly without history of BC on age, index VVA year, geographic region, Charlson Comorbidity categories, and follow-up time. BC after the index treatment was identified by BC diagnosis codes, mastectomy, chemotherapy, or radiation procedure. Incidence rate, rate ratio (RR) and their 95 % confidence intervals (CI) were calculated. The process was repeated to estimate BC recurrence in patients with a history of BC in 1:1, 1:2 and 1:3 matches.. 1728 ospemifene users and 3456 untreated patients met the inclusion and matching criteria for assessing incidence. The average number of days for which ospemifene was supplied was 314 (standard deviation [SD] = 340). Average follow-up time from index treatment was 937 days (SD = 392) for treated patients and 915 days (SD = 396) for controls. BC incidence rates per 1000 person-years was 2.03 (95 % CI: 1.06-3.91) for treated patients and 3.53 (95 % CI: 2.49-4.99) for controls (RR = 0.58, 95 % CI: 0.28-1.21). No difference in recurrence was observed between ospemifene-treated and matched untreated patients. Ten (32.3 %) treated vs. 25 (40.3 %) controls in the 1:2 matched analysis had a recurrence.. No differences were observed in the BC incidence and recurrence rates in ospemifene users compared with matched controls.

    Topics: Atrophy; Breast Neoplasms; Female; Humans; Incidence; Middle Aged; Neoplasm Recurrence, Local; Retrospective Studies; Risk Factors; Selective Estrogen Receptor Modulators; Tamoxifen; Vulva

2020
Repurposing ospemifene for potentiating an antigen-specific immune response.
    Menopause (New York, N.Y.), 2017, Volume: 24, Issue:4

    Ospemifene, an estrogen receptor agonist/antagonist approved for the treatment of dyspareunia and vaginal dryness in postmenopausal women, has potential new indications as an immune modulator. The overall objective of the present series of preclinical studies was to evaluate the immunomodulatory activity of ospemifene in combination with a peptide cancer vaccine.. Immune regulating effects, mechanism of action and structure activity relationships of ospemifene and related compounds were evaluated by examining expression of T-cell activating cytokines in vitro, and antigen-specific immune response and cytotoxic T-lymphocyte activity in vivo. The effects of ospemifene (OSP) on the immune response to a peptide cancer vaccine (PV) were evaluated after chronic [control (n = 22); OSP 50 mg/kg (n = 16); PV (n = 6); OSP+PV (n = 11)], intermittent [control (n = 10); OSP 10 and 50 mg/kg (n = 11); PV (n = 11); combination treatment (n = 11 each dose)] and pretreatment [control; OSP 100 mg/kg; PV 100 μg; combination treatment (n = 8 all groups)] ospemifene oral dosing schedules in a total of 317 mixed-sex tumor-bearing and nontumor-bearing mice.. The results showed that ospemifene induced expression of the key TH1 cytokines interferon gamma and interleukin-2 in vitro, which may be mediated by stimulating T-cells through phosphoinositide 3-kinase and calmodulin signaling pathways. In combination with an antigen-specific peptide cancer vaccine, ospemifene increased antigen-specific immune response and increased cytotoxic T-lymphocyte activity in tumor-bearing and nontumor-bearing mice. The pretreatment, intermittent, and chronic dosing schedules of ospemifene activate naive T-cells, modulate antigen-induced tolerance and reduce tumor-associated, pro-inflammatory cytokines, respectively.. Taken together, ospemifene's dose response and schedule-dependent immune modulating activity offers a method of tailoring and augmenting the efficacy of previously failed antigen-specific cancer vaccines for a wide range of malignancies.

    Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Calmodulin; Cancer Vaccines; Carcinogenesis; Chromones; Cytokines; Drug Administration Schedule; Drug Repositioning; Female; Flavonoids; Gene Expression; Humans; Immunologic Factors; Interferon-gamma; Interleukin-2; Jurkat Cells; Lung Neoplasms; Lymphocyte Activation; Membrane Glycoproteins; Mice; Mice, Transgenic; Morpholines; Mucin-1; Phosphatidylinositol 3-Kinases; RNA, Messenger; Signal Transduction; Structure-Activity Relationship; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Regulatory; Tamoxifen; Trifluoperazine

2017
The response to ospemifene in normal human breast tissue cultures.
    Menopause (New York, N.Y.), 2016, Volume: 23, Issue:7

    Topics: Breast; Breast Neoplasms; Humans; Selective Estrogen Receptor Modulators; Tamoxifen

2016
Design, synthesis and evaluation of Ospemifene analogs as anti-breast cancer agents.
    European journal of medicinal chemistry, 2014, Oct-30, Volume: 86

    The synthesis of some novel Ospemifene derived analogs and their evaluation as anti-breast cancer agents against MCF-7 (ER-positive) and MDA-MB-231 (ER-negative) human breast cancer cell lines are described. Few of these analogs for instance, compounds 6, 7 and 8 are shown to be more effective than recent Selective Estrogen Receptor Modulators (SERMs) i.e. Ospemifene and Tamoxifen, against these cell lines. Compound 8 was relatively more cytotoxic to MCF-7 cells similar to Ospemifene and Tamoxifen, while most potent compounds 6 and 7 were equally effective in inhibiting growth of both ER-positive and ER-negative cell lines. The observed activity profiles were further supported by the docking studies performed against estrogen receptors (ERα and ERβ). Compounds 6, 7 and 8 exhibited stronger binding affinities with both ERα and ERβ compared to Ospemifene and Tamoxifen.

    Topics: Antineoplastic Agents; Breast Neoplasms; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Drug Design; Drug Screening Assays, Antitumor; Humans; MCF-7 Cells; Models, Molecular; Molecular Structure; Structure-Activity Relationship; Tamoxifen; Tumor Cells, Cultured

2014
Selective estrogen receptor modulators inhibit growth and progression of premalignant lesions in a mouse model of ductal carcinoma in situ.
    Breast cancer research : BCR, 2005, Volume: 7, Issue:6

    Ductal carcinoma in situ (DCIS) is a noninvasive premalignant lesion and is considered a precursor to invasive carcinoma. DCIS accounts for nearly 20% of newly diagnosed breast cancer, but the lack of experimentally amenable in vivo DCIS models hinders the development of treatment strategies. Here, we demonstrate the utility of a mouse transplantation model of DCIS for chemoprevention studies using selective estrogen receptor modulators (SERMs). This model consists of a set of serially transplanted lines of genetically engineered mouse mammary intraepithelial neoplasia (MIN) outgrowth (MIN-O) tissue that have stable characteristics. We studied the ovarian-hormone-responsiveness of one of the lines with a particular focus on the effects of two related SERMs, tamoxifen and ospemifene.. The estrogen receptor (ER) status and ovarian-hormone-dependence of the mouse MIN outgrowth tissue were determined by immunohistochemistry and ovarian ablation. The effects of tamoxifen and ospemifene on the growth and tumorigenesis of MIN outgrowth were assessed at 3 and 10 weeks after transplantation. The effects on ER status, cell proliferation, and apoptosis were studied with immunohistochemistry.. The MIN-O was ER-positive and ovarian ablation resulted in reduced MIN-O growth and tumor development. Likewise, tamoxifen and ospemifene treatments decreased the MIN growth and tumor incidence in comparison with the control (P < 0.01). Both SERMs significantly decreased cell proliferation. Between the two SERM treatment groups, there were no statistically significant differences in MIN-O size, tumor latency, or proliferation rate. In contrast, the ospemifene treatment significantly increased ER levels while tamoxifen significantly decreased them.. Tamoxifen and ospemifene inhibit the growth of premalignant mammary lesions and the progression to invasive carcinoma in a transplantable mouse model of DCIS. The inhibitory effects of these two SERMs are similar except for their effects on ER modulation. These differences in ER modulation may suggest different mechanisms of action between the two related SERMs and may portend different long-term outcomes. These data demonstrate the value of this model system for preclinical testing of antiestrogen or other therapies designed to prevent or delay the malignant transformation of premalignant mammary lesions in chemoprevention.

    Topics: Animals; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Chemoprevention; Disease Progression; Female; Humans; Mammary Neoplasms, Experimental; Mice; Neoplasm Invasiveness; Receptors, Estrogen; Selective Estrogen Receptor Modulators; Tamoxifen

2005
In vitro and in vivo biologic effects of Ospemifene (FC-1271a) in breast cancer.
    The Journal of steroid biochemistry and molecular biology, 2001, Volume: 77, Issue:4-5

    Ospemifene (FC-1271a) is a novel selective estrogen receptor modulator under development for osteoporosis prevention. In the present paper, we examine both the in vitro and in vivo effects of FC-1271a in breast cancer models. In vitro, the growth inhibitory effects of FC-1271a and its main metabolite are investigated in MCF-7 and MDA-MB-231 human breast cancer cells at doses ranging from 0.1 to 10 microM. Modulation of pS2 expression, an indicator of estrogen activity, was also examined in all experiments using reverse transcription-polymerase chain reaction. In vivo, the effects of treatment with 10, 25, 50, or 100 mg/kg FC-1271a on MCF-7 and MDA-MB-231 human tumor xenografts in athymic, ovariectomized mice were determined. For MCF-7 cells, FC-1271a and its main metabolite, toremifene VI (TOR VI) displayed anti-estrogenic effects in vitro as shown through growth inhibition and decreased expression of pS2. Treatment with FC-1271a in vivo inhibited MCF-7 tumor growth, compared with control (P< or =0.05). FC-1271a and TOR VI did not inhibit the growth of MDA-MB-231 cells in vitro, and no clear effects of FC-1271a treatment were seen on MDA-MB-231 tumor growth in vivo. In conclusion, FC-1271a appears to exert anti-estrogenic effects dependent on estrogen receptor positivity in vitro and in vivo on the growth of MCF-7 cells.

    Topics: Animals; Breast Neoplasms; Cell Division; Chromatography, High Pressure Liquid; Disease Models, Animal; DNA, Complementary; Estrogen Antagonists; Female; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Neoplasms, Experimental; Polymerase Chain Reaction; RNA, Neoplasm; Selective Estrogen Receptor Modulators; Tamoxifen; Transplantation, Heterologous; Tumor Cells, Cultured

2001
Selective estrogenic effects of a novel triphenylethylene compound, FC1271a, on bone, cholesterol level, and reproductive tissues in intact and ovariectomized rats.
    Endocrinology, 2000, Volume: 141, Issue:2

    FC1271a is a novel triphenylethylene compound with a tissue-selective profile of estrogen agonistic and weak antagonistic effects. It specifically binds to the estrogen receptor alpha and beta with affinity closely similar to that of toremifene and tamoxifen. To study the in vivo effects of the compound, 4-month-old rats were sham operated (sham) or ovariectomized (OVX) and treated daily for 4 weeks with various doses of FC1271a or vehicle (orally). FC1271a was able to oppose OVX-induced bone loss by maintaining the trabecular bone volume of the distal femur. Accordingly, the OVX-induced loss of bone strength was prevented at doses of 1 and 10 mg/kg. FC1271a also prevented the OVX-induced increase in serum cholesterol in a dose-dependent manner. No significant changes in uterine wet weight or morphology were observed in the OVX-rats treated with 0.1 or 1 mg/kg FC1271a, but at a dose of 10 mg/kg it had a slightly estrogenic effect. In immature rats the effect of FC1271a on uterine wet weight was less stimulatory than that of toremifene or tamoxifen, but more stimulatory than that of raloxifene or droloxifene. The appearance of the dimethylbenzanthracene (DMBA)-induced mammary tumors was inhibited by treatment of DMBA-treated rats with FC1271a in a dose-dependent manner. In human MCF-7 breast cancer cell tumors raised in nude mice in the presence of estrogen, the growth and expression of pS2 marker gene could not be maintained after estrogen withdrawal by treatment with FC1271a. No formation of DNA adducts was observed in the liver of the FC1271a-treated rats. In conclusion, the bone-sparing, antitumor, and cholesterol-lowering effects of FC1271a combined with a low uterotropic activity and lack of liver toxicity indicate that FC1271a could be an important alternative in planning antiosteoporosis therapy for estrogen deficiency.

    Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Bone and Bones; Breast Neoplasms; Cholesterol; Estrogen Antagonists; Female; Humans; Mammary Neoplasms, Experimental; Mice; Mice, Nude; Organ Size; Osteoporosis; Ovariectomy; Raloxifene Hydrochloride; Rats; Rats, Sprague-Dawley; Reference Values; Tamoxifen; Toremifene; Transplantation, Heterologous; Tumor Cells, Cultured; Uterus

2000
Genotoxic effects of the novel mixed antiestrogen FC-1271a in comparison to tamoxifen and toremifene.
    Breast cancer research and treatment, 2000, Volume: 60, Issue:1

    Tamoxifen has been used for the treatment of breast cancer since the 1970s, but is considered a carcinogen because it has been linked to liver cancer in rats and an increased risk of endometrial cancer in patients. In rats, DNA adducts appear to be responsible for carcinogenesis, but their contribution to carcinogenesis in humans is not clear. FC-1271a and toremifene are mixed antiestrogens similar to tamoxifen. In order to compare the genotoxicity of these different triphenylethylenes, we treated mice for 28 days with 50 mg/kg of either tamoxifen, toremifene, FC- 1271 a or vehicle control. DNA from liver and uterus was assayed by standard 32P-postlabeling and thin layer chromatography for the presence of DNA adducts. Two methods of drug administration (oral and subcutaneous) and two strains of mice were compared and the plasma and tissue concentrations of the drugs and three metabolites of tamoxifen and toremifene were determined. Regardless of the conditions, only tamoxifen-treated mice showed DNA adducts in the liver. Adduct levels did not correlate with drug or metabolite levels and adducts were present even when drug was not detectable. Mice were also treated orally with either 50, 100, or 200 mg/kg of drug for 7 days. Again, adducts were found only in liver tissue of mice treated with tamoxifen, and adduct levels were dose-dependent. In conclusion, the chlorinated triphenylethylene FC-1271a did not cause DNA adducts under various conditions in mice, suggesting a low carcinogenic potential.

    Topics: Administration, Oral; Animals; Antineoplastic Agents, Hormonal; Breast Neoplasms; Carcinogens; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; DNA Adducts; Dose-Response Relationship, Drug; Estrogen Antagonists; Female; Humans; Injections, Subcutaneous; Liver; Mice; Mice, Inbred ICR; Mice, Inbred Strains; Spleen; Tamoxifen; Toremifene; Uterus

2000
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