RUTH: Raloxifene cuts breast cancer risk but increases risk of stroke

Results of the randomized Raloxifene Use for the Heart study showed that the drug was not associated with heart disease and that it reduced the risk of breast cancer and vertebral fracture. However, it increased the risk of thromboembolism and stroke, according to RUTH Trial researchers.Raloxifene powder

“The effect of raloxifene [Evista, Lilly], a selective estrogen-receptor modulator, on coronary heart disease (CHD) and breast cancer is not established,” wrote Elizabeth Barrett-Connor, MD, from the University of California, San Diego, and a RUTH trial investigator. “Raloxifene therapy has been associated with improvement in the levels of serum lipoprotein cholesterol, fibrinogen and homocysteine. The favorable effect of raloxifene on markers of cardiovascular risk, coupled with evidence from observational studies that treatment with estrogen was associated with a reduced risk of CHD in postmenopausal women, led to the design of the RUTH trial to determine the effect of raloxifene on clinical coronary events.”

In an accompanying editorial, Marcia L. Stefanick, PhD, from Stanford School of Medicine in California, said that for women with increased risk for CHD, the moderate benefits of raloxifene for breast cancer prophylaxis do not seem to justify the risks.

“The report by Barrett-Connor and colleagues highlights the need to consider the risk of breast cancer as well as other risks and coexisting conditions in determining whether and when raloxifene or another [selective estrogen-receptor modulator] is warranted for an individual woman,” Stefanick said. “For now, there is no magic bullet that can reduce the risks of major health problems related to estrogens and aging without introducing other potentially serious health concerns.”
The researchers randomized 10,101 postmenopausal women with CHD or multiple risk factors for CHD to receive 60 mg of daily raloxifene or placebo. The median follow-up was 5.6 years. The two main endpoints were coronary events, defined as death from coronary causes, myocardial infarction, hospitalization for an acute coronary syndrome and invasive breast cancer.

Compared with placebo, raloxifene had no significant effect on the risk for primary coronary events: 533 vs. 553 events (HR=0.95). However, it was associated with lower risk for invasive breast cancer: 40 cases with raloxifene vs. 70 cases with placebo (HR=0.56). This benefit was primarily accounted for by a reduced risk for estrogen-receptor–positive invasive breast cancers.

The rates of death from any cause or total stroke were not significantly different between groups. However, raloxifene was associated with a 49% increased risk for fatal stroke and a 44% increased risk for venous thromboembolism. Raloxifene was associated with 35% reduction in the risk for clinical vertebral fractures.
In postmenopausal women with CHD or at increased risk for CHD, treatment with raloxifene for a median of 5.6 years reduced the risk of invasive breast cancer and did not change the incidence of coronary events,” the authors reported in The New England Journal of Medicine.

“In these women, the difference in the absolute rates of events that were decreased (ie, breast cancer and clinical vertebral fractures) was similar to the difference in the absolute rates of events that were increased (ie, venous thromboembolic events and fatal strokes). When considering the use of raloxifene in a postmenopausal woman, the clinician should take into account the individual woman’s risk of disease and her personal preferences, and weigh potential benefits against risks and against the availability of alternative interventions.”