USPSTF Recommends Risk-Reducing Medication Use in Women at Increased Risk of Breast Cancer

The US Preventive Services Task Force is recommending¹ that providers offer medications that reduce the risk of breast cancer to women who are at an increased risk of the disease and at low risk for adverse effects related to the medications.

The task force handed a B recommendation for use of the medications in these women based on “convincing evidence” that they offer at least moderate benefit for reducing the risk of invasive estrogen receptor-positive breast cancer in postmenopausal women at an increased risk of the disease.

However, the task force recommended against prescribing these medications, which include tamoxifen, raloxifene, or aromatase inhibitors, to women who do not have an increased risk of breast cancer, explaining that the benefits of these medications “are no greater than small in women not at an increased risk for the disease.”

The recommendation applies to asymptomatic women aged 35 years or older, including those with previous benign breast lesions on biopsy; it does not apply to women who have a current or previous diagnoses of breast cancer or ductal carcinoma in situ.

The recommendation is similar to the task force’s 2013 recommendation, except for the addition of aromatase inhibitors to its recommended medications.

Despite these recommendations, and the significant amount of evidence supporting them, prescribing risk-reducing medications for breast cancer is uncommon among primary care providers, with 10% to 30% of providers reporting ever prescribing the medications for primary prevention of the disease, and most having only done so a few times.

A meta-analysis of 26 studies found that just 16.3% of women at increased risk for breast cancer used these medications, and other studies have found that even women who are aware of the risks and benefits don’t have interest in taking the medications, with concerns over the potential harms

These potential harms were acknowledged by USPSTF, who included in the recommendation that tamoxifen and raloxifene are associated with small to moderate harms, including an increased risk of venous thromboembolic events. The risk is greater for tamoxifen than for raloxifene, and the potential harms are greater in older women than in younger women. Tamoxifen, according to the task force, also increases the risk of cataracts.

They also cited adequate evidence linking aromatase inhibitors to vasomotor symptoms, gastrointestinal symptoms, musculoskeletal pain, and possible cardiovascular events, including stroke.

In an accompanying editorial, Lydia E. Pace, MD, MPH, assistant professor of medicine, Division of Women's Health and Division of General Internal Medicine, Brigham and Women's Hospital; and Nancy Keating, MD, MPH, professor of health care policy, Harvard Medical School, and practicing general internist, Brigham and Women's Hospital, praised the recommendation for its focus on the need to identify in which women the benefits outweigh the harms.²

Several randomized controlled trials (RCTs) have defined high risk as an estimated 5-year breast cancer risk of at least 1.66%, which, according to the pair, is the same risk faced by a women aged 60 years. Following this risk threshold, a 50% reduction over 5 years would correspond to a risk reduction of 0.83%, and 120 women would need to be treated to prevent 1 case of breast cancer. By using higher threshold, such as those with a 5-year risk of 3%, there would likely be more women who would benefit than experience harm.

“Understanding which women are more likely to experience benefits and harms is of paramount importance to guide clinician recommendations and patient decisions,” wrote the pair. They added, “However, existing evidence provides limited guidance.”

According to Pace and Keating, RCTs have shown greater breast cancer risk reduction in some subgroups, such as women with atypical hyperplasia and lobular carcinoma in situ, but other subgroup analyses have yielded little insight. They also argue that there is limited research on risk-reducing medications among the highest-risk women, including those with BRCA1/2 mutations.

They add that most participants in prevention trials are white, highlighting the need for more research in diverse and higher-risk populations to identify which women will likely benefit and which will likely experience harm from these medications.

References

1. US Preventive Services Task Force. Medication use to reduce the risk of breast cancer; US PReventive Services Task Force recommendation statement [published online September 3, 2019]. JAMA. doi:10.1001/jama.2019.11885.
2. Pace L, Keating N. Medications to reduce breast cancer risk; promise and limitations [published online September 3, 2019]. JAMA. doi:10.1001/jama.2019.9689.