Follow-up of the breast cancer prevention trial and the future of breast cancer prevention efforts.

Women who are at increased risk for developing breast cancer can be identified using quantitative risk assessment models that provide valid estimates of risk. The Breast Cancer Prevention Trial (BCPT, P-1) demonstrated that tamoxifen can reduce the incidence of both invasive and noninvasive breast cancer as well as of bone fractures in women at increased risk. These benefits accrue at the expense of increased risk of endometrial cancer, thromboses, cataracts, and possibly diminished quality of life in postmenopausal women. All premenopausal women with a 5-year risk of developing invasive breast cancer greater than 1.67% derive net benefit from using tamoxifen to reduce the risk. Subset analyses of older postmenopausal women taking raloxifene for the treatment of osteoporosis indicate reduction of breast cancer incidence by more than 70%. These findings led the National Surgical Adjuvant Breast and Bowel Project (NSABP) to design and launch the STAR trial (P-2, the Study of Tamoxifen and Raloxifene). Eligible women are at least 35 years of age and postmenopausal, and they must have either lobular carcinoma in situ (LCIS) or a 5-year risk of invasive breast cancer of at least 1.67% as determined by the Gail model [M. H. Gail et al., J. Natl. Cancer Inst. (Bethesda), 81: 1879-1886, 1989]. Subjects are randomly assigned to receive either tamoxifen 20 mg or raloxifene 60 mg daily in a double-blind, double-dummy design. The trial is designed to recruit a total of 22,000 postmenopausal women and is powered to demonstrate superior efficacy of either agent or their equivalence in reducing the incidence of primary breast cancer. Additional end points will include the incidence of cardiovascular events and bone fractures. Thromboembolic events and endometrial cancer are the predicted toxicities. Ancillary studies of cognitive function will also be performed. Raloxifene should not be used for the reduction of breast cancer risk outside the context of the STAR trial.