Breast cancer chemoprevention. Tamoxifen: current issues and future prospective.

Intervention clinical trials are under way to address whether tamoxifen can prevent breast cancer development. This effort is based on laboratory evidence that tamoxifen interferes with the initiation and promotion of mammary cancer, clinical evidence of decreased breast cancer incidence in the opposite breast of women participating in tamoxifen adjuvant breast cancer trials, and a favorable toxicity profile of tamoxifen providing reasonable assurance of drug safety when used in a population without cancer. The apparently favorable effects of tamoxifen on lipid metabolism and bone mineral density provide additional impetus to this evaluation. Potentially life threatening toxicity of thromboembolism and development of a second cancer remain concerns. With respect to implications of such clinical trials, even upon successful study completion, difficult issues will remain; these issues include the potential for interaction between tamoxifen and dietary fat reduction (also proposed as potential breast cancer prevention), the cost and cost-effectiveness of wide scale (or selective) implementation of positive results, and the generalizability of study results to socioeconomically disadvantaged and racial and ethnic minority populations that historically have been under-represented in medical clinical trials. These important issues should be addressed concurrently as large-scale prevention trials go forward to optimize the practical utility of efficacy data obtained.