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September 03, 2019
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USPSTF recommends preventive drugs for women at high breast cancer risk

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The U.S. Preventive Services Task Force today recommended that clinicians offer breast cancer risk-reducing medications such as tamoxifen, raloxifene and aromatase inhibitors to asymptomatic women aged 35 years and older who are at elevated risk for developing the disease and low risk for adverse effects from the treatments.

This recommendation received a B grade. The task force also recommended against, with a D grade, use of such medicines among women not at high risk for breast cancer.

“There are medications available that can help some women prevent breast cancer, but they are not for everyone,” USPSTF member Michael J. Barry, MD, director of the Informed Medical Decisions Program at Massachusetts General Hospital and professor of medicine at Harvard Medical School, said in a press release. “For women who are at increased risk for breast cancer, these medications can be beneficial and reduce their risk.”

The statement, published simultaneously with an evidence report in JAMA, serves as an update to the 2013 USPSTF recommendation on medications for women to reduce their risk for primary invasive breast cancer.

Investigators for the task force reviewed reference lists in the Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, EMBASE and MEDLINE between Jan. 1, 2013, and Feb. 1, 2019, and selected discriminatory accuracy studies of breast cancer risk evaluation methods; randomized clinical trials of tamoxifen, raloxifene and aromatase inhibitors for the prevention of primary breast cancer; and studies addressing adverse effects of the medications. They gathered data on methods, participant traits, inclusion criteria, outcome determination and follow-up, and pooled results of the individual trials using a random-effects model.
among individuals; incidence of breast cancer, fractures, thromboembolic events, coronary disease events, stroke, endometrial cancer and cataracts; and mortality served as the main outcomes.

The analysis included 46 studies involving more than 5 million participants. In 25 studies, 18 methods of risk assessment demonstrated low accuracy in predicting breast cancer likelihood among individuals (area under the curve, 0.55-0.65).
Results of placebo-controlled trials showed an association between the following medications and decreased incidence of invasive breast cancer: tamoxifen (risk ratio [RR] = 0.69; 95% CI, 0.59-0,84; four trials; n = 28,421); raloxifene (RR = 0.44; 95% CI, 0.24-0.8; two trials; n = 17,806); and the aromatase inhibitors exemestane and anastrozole (RR = 0.45; 95% CI, 0.26-0.7; two trials; n = 8,424).

One trial reported a higher risk for invasive breast cancer with raloxifene vs. tamoxifen after long-term follow-up (RR = 1.24; 95% CI, 1.05-1.47; n = 19,747), whereas two trials (n = 16,929) showed a lower risk for vertebral fractures with raloxifene (RR = 0.61; 95% CI, 0.53-0.73). One trial (n = 13,388) reported lower risk for nonvertebral fractures with tamoxifen vs. placebo (RR = 0.66; 95% CI, 0.45-0.98).

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Compared with placebo, tamoxifen and raloxifene appeared associated with increased thromboembolic events, with tamoxifen associated with more events than raloxifene and higher risk for endometrial cancer and cataracts than placebo.

“We all want to find better ways to prevent breast cancer, and it’s important that clinicians talk with patients about their level of risk and carefully consider the best approach,” USPSTF member Carol M. Mangione, MD, chief of the division of general internal medicine and health services research at the David Geffen School of Medicine at University of California, Los Angeles, said in the press release. “For women who are not at increased risk for breast cancer, these medications are not recommended because they may be more harmful than beneficial.”

As this recommendation becomes part of clinical practice, it will be important to develop more precise methods for identifying women most at risk for invasive breast cancer, according to a related editorial by Lydia E. Pace, MD, MPH, associate physician in the division of general internal medicine at Brigham and Women’s Hospital, and Nancy L. Keating, MD, MPH, professor of health care policy and medicine at Harvard Medical School and physician at Brigham and Women’s Hospital.

“Given the barriers to use, including the harms associated with a preventive treatment with moderate benefit, more accurate identification of women most likely to benefit or experience harm could help to focus preventive efforts on the clinical situations in which these medications will have most effect,” the authors wrote. “Ideally, this requires both more accurate risk prediction and studies powered to compare benefits and harms between subgroups. Meanwhile, considering risk-reducing medications for women with 5-year risk greater than 3% seems reasonable, as well as for women with atypical hyperplasia and lobular carcinoma in situ.” – by Jennifer Byrne

Disclosures: The researchers report no relevant financial disclosures. The editorial authors report no relevant financial disclosures.