In vitro and in vivo biologic effects of Ospemifene (FC-1271a) in breast cancer

Ospemifene (FC-1271a) is a novel selective estrogen receptor modulator unde r 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 metabolit e are investigated in MCF-7 and MDA-MB-231 human breast cancer cells at dos es ranging from 0.1 to 10 muM. Modulation of pS2 expression, an indicator o f estrogen activity, was also examined in all experiments using reverse tra nscription-polymerase chain reaction. In vivo, the effects of treatment wit h 10, 25, 50, or 100 mg/kg FC-1271a on MCF-7 and MDA-MB-231 human tumor xen ografts in athymic, ovariectomized mice were determined. For MCF-7 cells, F C-1271a and its main metabolite, toremifene VI (TOR VI) displayed anti-estr ogenic effects in vitro as shown through growth inhibition and decreased ex pression of pS2. Treatment with FC-1271a in vivo inhibited MCF-7 tumor grow th, compared with control (P less than or equal to 0.05). FC- 1271a and TOR VI did not inhibit the growth of MDA-MB-231 cells in vitro, and no clear e ffects 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. (C) 2001 Elsevier Science Ltd. All rights reserved.