The science of selective estrogen receptor modulators: concept to clinical practice.

Lippman et al. (1) assess the effect of raloxifene on the incidence of breast cancer in women with defined risk factors. However, raloxifene is used in clinical practice for the treatment and prevention of osteoporosis in postmenopausal women. To the casual observer, the application of a medicine to treat and prevent osteoporosis would seem to be counterintuitive as estrogen is known to build bones. It therefore follows that if estrogens build bones in postmenopausal women and estrogens support breast cancer growth (2), then why is there a reported decrease in breast cancer in women taking raloxifene to treat osteoporosis (3, 4)? The reason is that the class of drugs originally known as ‘‘nonsteroidal antiestrogens’’ are in fact selective estrogen receptor (ER) modulators (SERM), which turn on or turn off target sites around a woman’s body. The recognition of targeted estrogenic and antiestrogenic actions for the two principal players tamoxifen and raloxifene was defined in the latter half of the 1980s (Fig. 1; ref. 5). The concept being tested by Lippman et al. (1) is the roadmap described at the end of the 1980s (2, 6) and used by the pharmaceutical industry to develop numerous new SERMs as potential multifunctional medicines (7).