Safety and efficacy of antiestrogens for prevention of breast cancer.

The rationale for clinical trials of antiestrogens for prevention of breast cancer, potential concerns with antiestrogens, and clinical trials of antiestrogens for breast cancer prevention are discussed. Extensive preclinical evidence supports clinical investigation and use of tamoxifen for preventing breast cancer. The efficacy of tamoxifen in the treatment of advanced breast cancer and as adjuvant therapy has further strengthened the rationale for use in prevention. Tamoxifen is well tolerated and, like raloxifene, has been associated with non-cancer-related benefits. The major concerns with tamoxifen are an increased risk of thromboembolic events and endometrial cancer and an association with ocular disorders. Little is known about the long-term safety of raloxifene. Three randomized, double-blind, placebo-controlled clinical trials of tamoxifen 20 mg (as the citrate) daily for the prevention of breast cancer and one post hoc analysis and a literature review examining the effect of raloxifene on breast cancer risk (as a secondary endpoint) have been published. In one of the three trials of tamoxifen, the rate of invasive breast cancer was reduced 49%; in the other two trials, no reduction in breast cancer was found. Raloxifene apparently reduced the frequency of breast cancer. On the basis of the positive tamoxifen trial, tamoxifen can be offered to women with a five-year projected risk of breast cancer of > or = 1.67%, as determined by the Gail model. Risks and benefits should be evaluated for each patient. Tamoxifen may offer some women protection against breast cancer. Raloxifene may also have a preventive role, but more study is needed.