Breast cancer prevention.

Epidemiological, experimental, and clinical data strongly support the possibility that breast cancer will be prevented by using anti-estrogenic interventions in healthy women. Three trials involving over 20,000 women have so far been reported using tamoxifen 20 mg/day or placebo in healthy women to chemoprevent breast cancer. The American National Surgical Adjuvant Breast and Bowel P-1 Project randomized over 13,000 women to take tamoxifen or placebo and showed a 49% reduction in the early incidence of breast cancer. This was associated with a reduction in osteoporotic fractures but increases in the risks of endometrial cancer, cataract, and thromboembolism. The Royal Marsden tamoxifen trial randomized 2,500 women, and the Italian national trial randomized 5,000 women. Interim analyses from these two trials showed no effect on the early incidence of breast cancer. These results, therefore, have not been able to clearly show an overall clinical benefit of giving tamoxifen to healthy women, nor have they shown which women are likely to benefit. Another selective anti-estrogen (SERM), raloxifene, has been used in a clinical trial to prevent osteoporotic fractures in women with low bone mineral density. Annual mammography in this trial has shown an approximate 80% reduction in the early incidence of breast cancer, and further follow-up of this trial continues. New trials in chemoprevention of breast cancer being started or being proposed use luteinizing-hormone-releasing hormone analogues, aromatase inhibitors, and other SERMs.