Tool Weighs Benefits, Risks of Raloxifene or Tamoxifen to Prevent Breast Cancer

Researchers have developed a benefit-risk index to help guide decisions on whether postmenopausal women at increased risk of developing breast cancer should take raloxifene or tamoxifen to reduce that risk. Although studies have shown that these drugs can reduce breast cancer risk, the drugs can also cause adverse side effects, so women and their physicians must decide whether the potential benefits of one or the other drug outweigh the risks in each patient’s particular situation.

The results of the benefit-risk analysis, reported online May 2, 2011, in the Journal of Clinical Oncology, showed that the risks and benefits of taking raloxifene or tamoxifen depend on a woman’s age, race/ethnicity, projected 5-year breast cancer risk, and whether she has had a hysterectomy. Overall, the analysis showed that raloxifene is better than tamoxifen for reducing breast cancer risk in women with a uterus. For women who have had a hysterectomy, the benefit-risk profiles for raloxifene and tamoxifen are similar.

Worta McCaskill-Stevens, M.D., of NCI’s Division of Cancer Prevention, Andrew Freedman, Ph.D., of NCI’s Division of Cancer Control and Population Sciences, and their colleagues used data from the Women’s Health Initiative, SEER, and two large clinical trials—the Breast Cancer Prevention Trial (BCPT) and the Study of Tamoxifen and Raloxifene (STAR) trial—that evaluated the ability of tamoxifen and raloxifene to prevent invasive breast cancer (IBC) in women at high risk for the disease. They considered non-breast cancer health outcomes, including bone fractures, blood clots, stroke, and endometrial cancer, rates of which were potentially increased or decreased by raloxifene or tamoxifen.

The researchers then assigned a weight to each possible health outcome, and to IBC and in situ breast cancer, and calculated the probability that a woman with various risk factors would have each outcome in 5 years with and without raloxifene or tamoxifen. They used these calculations to create color-coded tables for each drug that show, for each age group and 5-year projected risk of IBC, whether there is strong or moderate evidence that the benefits outweigh the risks or that the risks outweigh the benefits. The researchers created separate tables for white non-Hispanic, black, and Hispanic postmenopausal women 50 years of age or older, with and without a uterus.

“By using NCI’s Breast Cancer Risk Assessment Tool (BRCAT) to estimate the projected 5-year risk of IBC, a health care provider can obtain a benefit-risk index from the corresponding table entries,” the study authors wrote. “By combining this information with information on clinical features and personal preferences, the health care provider and patient can make an informed decision.”

In an accompanying editorial, Eitan Amir, M.D., and Pamela J. Goodwin, M.D., of the University of Toronto, described some limitations of the analysis but noted: “[This new tool is] the most comprehensive attempt to date to individualize chemoprevention by enabling clinicians to select tamoxifen or raloxifene for patients on the basis of a number of key patient attributes. This is a clear step forward for breast cancer prevention and may ultimately lead to improvement in uptake of chemoprevention strategies.”