Reduced incidence of invasive breast cancer with Raloxifene among women at increased coronary risk

Women who took raloxifene were less likely to develop invasive estrogen-receptor (ER) positive breast cancer compared with women who did not, according to data from a randomized controlled trial published online June 10 in the Journal of the National Cancer Institute. The drug did not reduce the risk of non-invasive cancer or invasive ER-negative cancers.

A previous analysis of data from the Raloxifene Use for the Heart (RUTH) trial, which enrolled women with coronary heart disease or those at an increased risk for the disease, showed that the drug did not protect against heart disease, which was one of the primary aims of the trial. But after a median follow up of 5.6 years, it did reduce the risk of invasive breast cancer by 44 percent, compared with women not taking the drug. Raloxifene is a selective estrogen receptor modulator (SERM), which might suggest that the drug would have a preferential effect on hormone-responsive breast cancers. The drug is approved by the FDA for the prevention and treatment of osteoporosis in postmenopausal women and for invasive breast cancer risk reduction in postmenopausal women with osteoporosis or at high risk for breast cancer.

To investigate the specific types and stages of breast cancer affected by raloxifene, as well as the timing of its action and the types of patients it can help, Deborah Grady, M.D., of the University of California at San Francisco and colleagues examined the RUTH trial data in more detail.

The 5,044 women who took raloxifene had a 55 percent reduction in the risk of developing invasive ER-positive breast cancer compared with the 5,057 women who took placebo. That is equivalent to an absolute reduction in risk of 1.2 cases per 1,000 women treated for one year. There was no reduction in the risk of invasive ER-negative breast cancer or in non-invasive breast cancers of any type. The researchers saw the same effects regardless of the women's age, prior hormone use, or baseline risk of breast cancer.

The reduction in breast cancer risk is consistent with findings from other trials that involved women without heart disease. Women who took raloxifene in the RUTH trial had an increased incidence of blood clots and fatal strokes compared with those who took placebo. Thus, the researchers conclude that women who are considering taking of raloxifene need to weigh the risks and benefits. "Assuming that the relative risks from the RUTH trial apply to women in the general population, the best benefit-to-risk ratio would occur in women at high risk of breast cancer and osteoporosis and low risk of venous thrombosis and stroke," the authors write.

In an accompanying editorial, V. Craig Jordan, Ph.D., D.Sc., of the Fox Chase Cancer Research Center in Philadelphia reviewed the clinical development of raloxifene and other SERMs. Laboratory data suggested that such drugs may be valuable in treating or preventing several diseases. Not all of the laboratory-generated hypotheses have held up in the clinic, but several have. "Overall, clinical evidence is accumulating that the SERMs hold great promise in being able to control multiple diseases," the editorialist writes.