Hormonal interventions to prevent hormonal cancers: breast and prostate cancers.

In 1998, the concept of breast cancer prevention became a reality with the approval of tamoxifen to reduce the risk of developing breast cancer in women at increased risk for the disease. This approval was based on decades of research on selective estrogen receptor modulators providing an understanding of the role of the estrogen receptor in breast cell growth, and an appreciation of the carcinogenic process. Although results from the Breast Cancer Prevention Trial demonstrated a 49% reduction in breast cancer in women at increased risk, there were associated toxicities related to the estrogenic effects of tamoxifen; that is, deep vein thrombosis, pulmonary embolism, and endometrial cancer. In an effort to improve its benefit-risk profile, tamoxifen is now being compared with raloxifene, a selective estrogen receptor modulator approved for the treatment and prevention of osteoporosis. This equivalency prevention Study of Tamoxifen and Raloxifene completed accrual of 19 747 high-risk postmenopausal women in November 2004. Meanwhile, another class of estrogen-directed drugs, the aromatase inhibitors, have shown efficacy in breast cancer adjuvant trials, spawning a number of prevention trials that have recently been initiated. As with breast cancer the hormonal contribution to prostate carcinogenesis was the basis for the Prostate Cancer Prevention Trial which showed that finasteride, an androgen antagonist, reduces the incidence of prostate cancer compared to placebo.