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June 16, 1999

Encouraging News From the SERM Frontier

Author Affiliations

Author Affiliations: The Prudential Center for Health Care Research (Dr Franks) and Molecular Biology Branch, Centers for Disease Control and Prevention (Dr Steinberg), Atlanta, Ga.

JAMA. 1999;281(23):2243-2244. doi:10.1001/jama.281.23.2243

The discovery that pharmacologic agents can be estrogenic in some tissues while antiestrogenic in others has led to intense interest in better understanding the mechanism by which molecular structure interacts with cellular receptors to selectively affect DNA transcription in different organs. Appreciation for these selective estrogen receptor modulators (SERMs) has inevitably given way to the hope of developing one that could confer all of the benefits of estrogen without any of its risks. The first widely used SERM, tamoxifen citrate, has been found to have the antiestrogenic effect of reducing risk for breast cancer as well as beneficial estrogenic effects on serum lipids and bone density in women.1 However, tamoxifen also has the undesirable antiestrogenic effect of causing hot flashes and the undesirable estrogenic effects of increasing risk for endometrial cancer and venous thromboembolism in women.1 Because raloxifene hydrochloride, a second-generation SERM, has been shown to increase women's bone density without increasing risk for endometrial cancer,2,3 results of clinical trials designed to study its protective effects against breast cancer have been eagerly awaited.