USPSTF Recommendations on BRCA Mutation Testing

Roxanne Nelson, RN, BSN

August 20, 2019

The US Preventive Services Task Force (USPSTF) has issued its final recommendation statement on risk assessment, genetic counseling, and genetic testing for BRCA-related cancers in women.

Potentially harmful mutations of the breast cancer susceptibility 1 and 2 genes (BRCA1/2) are associated with increased risk for breast, ovarian, fallopian tube, and peritoneal cancer, the Task Force explains.

In the general population, BRCA1/2 mutations occur in an estimated 1 in 300 to 500 women and account for 5% to 10% of breast cancer cases and 15% of ovarian cancer cases.

There is not enough evidence to screen all women for these mutations, but certain women are at increased risk, and it is these groups that are highlighted by the Task Force.

Previously, the Task Force has highlighted women with a family history of breast, ovarian, fallopian tube, or peritoneal cancer.

The new recommendations add two more groups: women with a personal history of breast, ovarian, fallopian tube, or peritoneal cancer, and women with ancestry associated with breast cancer related to BRCA1/2 gene mutations (eg, Ashkenazi Jews).

The USPSTF recommends that primary care clinicians should assess all these groups of women using an appropriate brief familial risk assessment tool.

Women with a positive result on the risk assessment tool should receive genetic counseling and, if indicated after counseling, genetic testing (B recommendation).

The recommendations were published online August 20 in JAMA.

"Some women can benefit from risk assessment, counseling, and testing, but not all women need these services," said Task Force Chair Douglas K. Owens, MD, in a statement.

"We suggest women talk to their clinicians and decide on the best next steps together," added Owens, who is also a general internist and investigator at the Center for Innovation to Implementation at the Veterans Affairs Palo Alto Health Care System, and professor of medicine at Stanford University, California.

"Because these tests are not without harms, testing for BRCA mutations in women without these risk factors is not recommended," said Task Force member Carol M. Mangione, MD, MSPH, in a statement.

The USPSTF also notes that current research on risk assessment and testing for BRCA1/2 mutations has largely focused on short-term outcomes for highly selected women at referral centers, and more research is needed to determine the best strategies for population-based risk assessment and testing.

Complex Genetic Testing Landscape

In an accompanying editorial, Susan Domchek, MD, from the University of Pennsylvania, Pittsburgh, and Mark Robson, MD, Memorial Sloan Kettering Cancer Center, New York City, point out that the implementation of BRCA1/2 testing is challenging, as recent changes in testing have added significant complexity.

Multigene panel testing (MGPT), with panels that can screen for 80 or more genes, has now largely replaced BRCA1/2 testing, they write. Although these large panels detect more pathogenic variants, they also detect more variants of uncertain significance with unclear associations of disease risk.

"The clinical utility of the indiscriminate use of MGPT has not been established, and genetics education of primary care clinicians has not kept pace with either the influx of new information or the changes in the genetic testing marketplace," they write.

The availability of direct-to-consumer testing is adding to the complexity of genetic testing. Although the option of genetic testing outside of the medical model could expand access for many individuals, the authors emphasize that "genetic testing, regardless of results, needs to be placed in the context of an individual's overall health to be of most value."

"As consideration of criteria for testing for BRCA1/2 pathogenic variants is broadened, it is important to recognize the evolving complexities of testing options and increase education for physicians and other healthcare professionals to navigate the landscape," they conclude. "In addition, uptake of testing among individuals at the highest risk must improve, and persistent disparities in testing must be resolved."

The Agency for Healthcare Research and Quality (AHRQ) support the operations of the USPSTF. Disclosure forms for USPSTF members can be viewed here. All members of the USPSTF receive travel reimbursement and an honorarium for participating in USPSTF meetings. Domchek has reported receiving personal fees from AstraZeneca, Clovis, and Bristol-Myers Squibb. Robson has reported receiving grants, personal fees, and nonfinancial support from AstraZeneca; nonfinancial support from Pfizer; personal fees from McKesson; and research support to his institution from Myriad Genetics (in kind), Invitae (in kind), AbbVie, Tesaro, and Pfizer.

JAMA. 2019;322:652-665; 619-621. Full text, Editorial

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