Tamoxifen to raloxifene and beyond

Tamoxifen, a selective estrogen receptor modulator (SERM), is the treatment of choice for all stages of hormone-responsive breast cancer and has been shown to prevent breast cancer in high-risk women. Despite acting as an antiestrogen on the breast, tamoxifen has partial estrogenic effects on other target tissues. These partial estrogen agonistic actions produce beneficial effects on bones and the lipid profile in postmenopausal women. However, tamoxifen is associated with an increase in endometrial cancer. Additionally, its antiestrogenic effects in the central nervous system result in hot flashes in postmenopausal women. Raloxifene is another SERM approved for the prevention of osteoporosis in postmenopausal women. Like tamoxifen, raloxifene appears to prevent breast cancer in high-risk women and has not, to date, been noted to increase the incidence of endometrial cancer. The Study of Tamoxifen and Raloxifene will compare the effects of the two agents on breast cancer prevention and endometrial cancer risk. A number of new agents are being developed for breast cancer treatment and prevention and osteoporosis prevention. These include other SERMs, selective estrogen receptor downregulators (SERDs), and aromatase inhibitors. It is hoped that one of these new agents will be the ideal agent, acting as an antiestrogen on breast and endometrium while having estrogenic effects on bones, the lipid profile, and the central nervous system. Semin Oncol 28:260-273.