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National Institute of Environmental Health Sciences

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Publication Detail

Title: Ospemifene inhibits the growth of dimethylbenzanthracene-induced mammary tumors in Sencar mice.

Authors: Wurz, Gregory T; Read, Karla C; Marchisano-Karpman, Cristina; Gregg, Jeffrey P; Beckett, Laurel A; Yu, Qilu; Degregorio, Michael W

Published In J Steroid Biochem Mol Biol, (2005 Nov)

Abstract: Ospemifene is a new selective estrogen receptor modulator (SERM) that is being developed for the treatment of urogenital atrophy and osteoporosis. Similarly to other SERMs, ospemifene exhibits antiestrogenic effects in breast tissue, which led to the hypothesis that it may be a potential breast cancer chemopreventive agent. We first assessed the ability of ospemifene, compared to tamoxifen and raloxifene, to prevent dimethylbenzanthracene (DMBA)-induced mammary tumors in female Sencar mice. Ospemifene (N = 18), tamoxifen (N = 20) and raloxifene (N = 17), each dosed at 50 mg/kg, were administered daily by oral gavage, in combination with 20 microg DMBA for the first 6 weeks. Control mice (N = 21) received vehicle plus DMBA only for the first 6 weeks. Daily treatment then continued for 37 weeks. As hypothesized, ospemifene greatly reduced the incidence of mammary carcinomas compared to control mice (p = 0.003), similar to tamoxifen (p = 0.0004); however, in the raloxifene group, no significant effect was seen in mammary tumor prevention (p = 0.20). A follow-up study comparing ospemifene (N = 20) to tamoxifen (N = 20) in the same model was then performed to confirm the results of the first study. The results of the follow-up study, which extended the treatment to 52 weeks, confirmed the results of our previous study, with ospemifene (p = 0.01) and tamoxifen (p = 0.004) significantly decreasing mammary carcinomas compared to controls. The results of these two studies suggest that women taking ospemifene for osteoporosis and/or urogenital atrophy may further benefit from ospemifene's breast cancer chemopreventive effects.

PubMed ID: 16153821 Exiting the NIEHS site

MeSH Terms: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents/therapeutic use*; Carcinoma/chemically induced; Carcinoma/prevention & control; Female; Mammary Neoplasms, Experimental/chemically induced; Mammary Neoplasms, Experimental/prevention & control*; Mice; Mice, Inbred SENCAR; Raloxifene Hydrochloride/chemistry; Raloxifene Hydrochloride/therapeutic use; Selective Estrogen Receptor Modulators/chemistry; Selective Estrogen Receptor Modulators/therapeutic use*; Tamoxifen/analogs & derivatives*; Tamoxifen/chemistry; Tamoxifen/therapeutic use

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