ospemifene and Disease-Models--Animal

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

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