Women at high risk for breast cancer may derive the most benefit with the least harms from preventive treatment with risk-reducing medications, according to the findings of an evidence review performed on behalf of the United States Preventive Services Task Force (USPSTF).

In 2002, the USPSTF recommended against routine use of risk-reducing medications in women at low or average risk for primary breast cancer. However, the panel also advised that clinicians discuss the potential benefits and harms of tamoxifen and raloxifene in reducing risk for primary breast cancer with women who are at high risk for the disease and low risk for adverse effects.

To update evidence of the effectiveness and adverse effects of these risk-reducing drugs for the USPSTF, Heidi D. Nelson, MD, MPH, and colleagues evaluated studies on the topic published through December 2012, reporting their results in Annals of Internal Medicine (2013;158:604-614). The USPSTF will consider the information in formulating an upcoming recommendation statement.       

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Overall, Nelson and associates learned that medications reduced the incidence of invasive breast cancer: Seven trials of good or fair quality indicated that compared with placebo, tamoxifen and raloxifene reduced incidence of invasive breast cancer by seven to nine cases in 1,000 women over the course of 5 years.

New results from the Study of Tamoxifen and Raloxifene (STAR) trial demonstrated that tamoxifen reduced breast cancer incidence more than did raloxifene, by five cases in 1,000 women, but neither drug reduced breast cancer–specific mortality or all-cause mortality rates. STAR also showed that both agents reduced the incidence of fractures.

Although trials demonstrated that women at all levels of breast cancer risk had a reduction in breast cancer incidence with tamoxifen, those at highest risk as indicated by risk scores or preexisting atypical hyperplasia benefited the most. Women who received tamoxifen, raloxifene, or exemestane had a 10-year breast cancer risk of 7.5%, compared with a 21.3% risk for women on no treatment.

Use of the risk-reducing drugs did, however, increase the incidence of thromboembolic events. In STAR, tamoxifen increased the incidence of thromboembolic events more than did raloxifene, by four cases in 1,000 women, and increased the incidence of endometrial cancer and cataracts compared with placebo and raloxifene.

Nelson’s team also found that use of these drugs is limited by their adverse effects and by the inaccuracy of methods to identify candidates. Trials provided limited and heterogeneous data on medication adherence and persistence, but the findings did indicate that many women do not take tamoxifen because of associated harms.