The endocrine prevention of breast cancer.

Breast cancer incidence is increasing in all parts of the world. Although in Western countries death rates are declining, there is a need to make attempts to prevent the disease in order to reduce the trauma of diagnosis and treatment. Endocrine approaches to breast cancer prevention have been the most successful approach to cancer prevention to date. Studies with tamoxifen were initiated when it was noted that, during adjuvant treatment after surgery to prevent relapse, the incidence of new contralateral cancers was reduced by half. Four trials of >or=5 years of tamoxifen compared with placebo in women at increased risk of breast cancer were initiated in the 1980s and showed a similar reduction in breast cancer, but only in oestrogen-receptor-positive disease. Recent follow-up indicated that there is a carry-over effect of tamoxifen after the completion of treatment at 5 years so that the preventive effect at 10 years is significantly great than at 5. The selective oestrogen receptor modulator (SERM) raloxifene has also been assessed as a preventive agent in two major international randomized trials compared with placebo and shows a protective effect similar to that of tamoxifen. An American study subsequently compared tamoxifen and raloxifene in a trial of nearly 20,000 women at increased risk (the STAR trial) and demonstrated that the two agents were equally effective but that the toxicity of raloxifene was less. Adjuvant trials comparing tamoxifen and the modern potent aromatase inhibitors (anastrozole, letrozole and exemestane) indicate that they are superior to tamoxifen and reduce contralateral breast cancer by approximately 70%. This observation has led to the initiation of two trials in postmenopausal women comparing anastrozole (the IBISII trial) or exemestane (the MAP-3 trial) with placebo. Currently it is recommended that tamoxifen is used to prevent breast cancer in premenopausal women and raloxifene for postmenopausal women (it is not effective in the premenopausal group),and we await the results of the aromatase inhibitor trials.