The U.S. Preventive Services Task Force (USPSTF) on Tuesday finalized new recommendations broadening the number of women primary care providers should asses for BRCA gene mutations that increase the risk of breast, ovarian, and other cancers.

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Background

BRCA genes participate in processes to repair damaged DNA and prevent tumors from developing. Mutations of the gene, however, have been tied to an increased risk of certain cancers, including breast cancer. According to the National Cancer Institute (NCI), BRCA mutations account for approximately 20% to 25% of hereditary breast cancers and approximately 5% to 10% of all breast cancers.

USPSTF in 2013 recommended primary care providers assess women who have a personal or family history of breast, ovarian, peritoneal, or tubal cancer for BRCA1 and BRCA2 mutations.

USPSTF broadens recommendations for assessing women for BRCA gene mutations

However, based on new evidence, USPSTF on Tuesday issued a final recommendation statement advising primary care providers to assess women who have personal or family histories of breast, ovarian, peritoneal, or tubal cancer for BRCA1 and BRCA2 mutations, as well as women who have ancestries—such as Ashkenazi Jewish descent—associated with BRCA1 and BRCA2 mutations.

USPSTF in the statement recommended women who receive positive test results on the primary care risk assessment then undergo genetic counseling, and possibly genetic testing for the mutations. USPSTF did not recommend a treatment for women who test positive for BRCA mutations. The task force instead recommended women receive a referral for a full discussion of their treatment options, which could include a mastectomy, intensive screening, and risk-reducing medications such as tamoxifen or aromatase inhibitors.

USPSTF updated the recommendation based on data from an evidence report, which included 103 published studies on the accuracy of risk assessments, interventions to lower the risk of BRCA-related cancer, and the outcomes of genetic counseling and testing. Based on the evidence, USPSTF concluded that assessing women for BRCA mutations when they have ancestries associated with the mutations or have had breast, ovarian, or tubal cancer provides a moderate benefit and poses small-to-moderate risks. USPSTF gave a "B" grade for such assessments. Under the Affordable Care Act, insurers are required to cover preventive services that receive a "B" grade or higher from USPSTF without cost sharing.

However, USPSTF in the statement did not recommend a routine risk assessment, genetic counseling, or genetic testing for women whose ancestry, family history, or personal history is not associated with BRCA1 or BRCA2 mutations. Ultimately, USPSTF gave a "D" grade for assessing women who do not have ancestral ties or a family or personal history associated with BRCA mutations.

Mixed reaction

Carol Mangione, a USPSTF member and a primary care physician at the University of California-Los Angeles, in an interview said, "BRCA1 and BRCA2 mutations are important to detect because they really significantly increase the risk for breast or ovarian cancer." However, she noted, "[T]hese mutations are actually pretty rare."

But some observers raised concerns about the new recommendations.

For instance, Susan Domchek of the University of Pennsylvania and Mark Robson of Memorial Sloan Kettering Cancer Center in an editorial accompanying the study suggested the recommendations could be more detailed. They raised concerns that the new recommendations do "not specifically endorse testing unaffected Ashkenazi Jewish women with no family history" for the mutations.

Rachel Yung of the University of Washington and Larissa Korde of NCI in an editorial published in JAMA Oncology wrote called the new recommendations a "missed opportunity" because they apply only to women, and "[m]etastatic prostate cancer is the most common BRCA-associated cancer in men." They continued, "Notably, 6% of men with metastatic prostate cancer have a BRCA1 or BRCA2 mutation."

Lisa Newman of New York-Presbyterian/Weill Cornell Medical Center in an editorial published in JAMA Surgery wrote that the recommendations "provid[e] an important service in recommending that primary care clinicians take a proactive stance in assessing risk for breast and ovarian cancer." However, she added that "it remains imperative for clinicians to exercise clinical judgment and to be mindful of patient subsets that do not necessarily fit into recommendations designed for the majority or general populations." For example, Newman noted USPSTF's recommendations do not address variations in tumor phenotypes among women with African ancestry because of the limited availability of research on the topic (Ingram, MedPage Today, 8/20; Neergaard, Associated Press, 8/20; Howard, CNN, 8/20).