Treatment with raloxifene (Evista) reduced the risk of receptor-positive invasive breast cancer by more than half among women enrolled in a randomized study of heart disease prevention. Patients randomized to the selective estrogen receptor modulator had 55% fewer invasive estrogen receptor-positive breast cancers than women in the placebo group, Deborah Grady, M.D., of the University of California San Francisco, and colleagues reported in the Journal of the National Cancer Institute.
The reduction in receptor-positive disease accounted for virtually all of the 44% overall reduction in invasive breast cancer previously reported from the study.
Neither invasive receptor-negative breast cancer nor noninvasive breast cancer was reduced by raloxifene treatment.
The findings also are consistent with those from a trial of raloxifene to prevent osteoporotic fractures in postmenopausal women.
"Raloxifene appeared to be most effective in reducing the incidence of breast cancer during the first four years of treatment," the authors said. "Moreover, the effect of treatment appeared to be similar across subgroups defined by age, reproductive history, and breast cancer risk status."
The findings came from the Raloxifene Use for the Heart (RUTH) trial, which involved 10,101 women with coronary heart disease or who were at high risk for CHD.
The primary results of the trial showed no effect of raloxifene on heart disease risk, but 44% overall reduction in the risk of invasive breast cancer.
The findings followed those from the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, which involved 7,705 postmenopausal women with osteoporosis. Among women treated for four years, raloxifene reduced the risk of invasive breast cancer by 72% compared with placebo.
In the current study, Dr. Grady and colleagues analyzed the RUTH data to determine the effects of raloxifene on breast cancer by histologic type, tumor stage, lymph node status, and tumor grade and size. The original findings from RUTH included a 44% reduction in the hazard ratio for invasive breast cancer in women treated with raloxifene. The reduction translated into the prevention of 1.2 invasive breast cancers per 1,000 women treated for one year.
Dr. Grady and co-authors found that the overall reduction in the risk of invasive breast cancer reflected a hazard ratio of 0.45 (95% CI 0.28 to 0.72) in the subgroup of women with hormone receptor-positive tumors. The magnitude of the overall reduction in the risk of invasive breast cancer was similar across subgroups defined by age, body mass index, family history of breast cancer, prior use of postmenopausal hormones, and five-year estimated risk of invasive breast cancer. Raloxifene was associated with an increased risk of venous thromboembolism and fatal stroke in RUTH. Assuming that the relative risks of the trial apply to women in the general population, the authors suggested the best risk:benefit ratio would occur in women with a high risk of breast cancer and osteoporosis and a low risk of venous thromboembolism and stroke. They also pointed out that participants in the RUTH trial were selected because they either had known coronary disease or were at high risk for coronary disease. "Thus, it is possible," they wrote, "that the ?ndings of the RUTH trial may not be able to be generalized to women who are not at high risk for coronary disease."