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.