USPSTF recommends chemoprevention for women at high risk for breast cancer

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1. Among high-risk women, the chemopreventative medications tamoxifen and raloxifene reduced the incidence of invasive breast cancer and fractures but increased the incidence of thromboembolic events. Neither medication impacted all-cause or breast cancer-specific mortality. 

2. While tamoxifen was more effective than raloxifene, it increased the incidence of thromboembolic events, endometrial cancer, and cataracts more than placebo or raloxifene. 

Evidence Rating Level: 1 (Excellent)

Study Rundown: This systematic review of chemoprevention of breast cancer found that tamoxifen and raloxifene provide benefit to women at the highest level of risk for breast cancer and recommends prophylaxis for those women at high risk for breast cancer and low risk of adverse events. Adverse events on these medications include clots, endometrial cancer and cataracts such that clinicians should discuss the pros and cons of chemoprophylaxis with patients. The findings of this review serve as an update to the 2002 U.S. Preventive Services Task Force (USPSTF) evidence-based recommendations. Further investigations are required to facilitate more concrete treatment recommendations in future USPSTF reports. In particular, studies to characterize mortality benefit, define optimal treatment dose and duration, and identify practical methods of recognizing high-risk women are needed.

Click to read the study in The Annals of Internal Medicine

Relevant Reading: UptoDate: Selective estrogen receptor modulators and aromatase inhibitors for breast cancer prevention

In-Depth [systematic review]: from the Agency for Healthcare Research and Quality (AHRQ) Effective Health Care Program included randomized, controlled trials, observational studies, and diagnostic accuracy studies of risk assessment. Studies from the last report in 2002 through December 5, 2012 were included. Two investigators independently reviewed each study, rated study quality and abstracted key data.

Composite data of four placebo-controlled trials in women without preexisting breast cancer found that tamoxifen prevented 7 cases of invasive breast cancer in 1000 women over 5 years (RR:0.70, CI:0.59-0.82). Two placebo-controlled trials found that raloxifene prevented 9 cases in 1000 women over 5 years (RR:0.44, CI:0.27-0.71). Head-to-head comparison of tamoxifen and raloxifene from the STAR (Study of Tamoxifen and Raloxifene) trial found that tamoxifen reduced breast cancer incidence more than raloxifene by 5 cases in 1000, but neither reduced mortality rates.  Both drugs were found to reduce the incidence of fractures by similar amounts, but tamoxifen increased the incidence of thromboembolic events, endometrial cancer, and cataracts more than placebo or raloxifene.

By Maren Shapiro and Leah Hawkins

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