Primary care physicians should not routinely refer all women for genetic counseling and DNA testing to detect the presence of specific BRCA1 and BRCA2 gene mutations that may be associated with breast or ovarian cancers, according to a new recommendation from the U.S. Preventive Services Task Force. However, if a woman has certain specific family history patterns that put her at risk for these gene mutations, her primary care physician should suggest counseling and possible DNA testing. This is the first time the Task Force has addressed the issue of genetic counseling and DNA-based genetic testing for any disease. These recommendations, along with a review of the supporting evidence, appeared in the September 6 issue of Annals of Internal Medicine.
BRCA1 and BRCA2 are genes that help control normal cell growth. Women who inherit specific changes or mutations in one or both of these genes have a greater risk of developing breast and/or ovarian cancer, especially if their family members have had one or both of these cancers. However, only a small number of women-about 2 percent-have the specific family history patterns that put them at risk for BRCA mutations. In the general population, only about 1 in 300 to 1 in 500 women are believed to have these harmful genetic mutations. Even among women with these mutations, not everyone will actually develop breast or ovarian cancer.
Women who are at an increased risk of inheriting the BRCA1 or BRCA2 gene mutations include those of Ashkenazi (predominantly Eastern European) Jewish descent with a first- or second-degree relative with breast or ovarian cancer. A first-degree relative could be a mother, sister, or daughter; a second-degree relative might be a grandmother or an aunt. Risk factors for women not of Ashkenazi Jewish background include having specific family history patterns, for example, multiple first- or second-degree relatives with breast and/or ovarian cancer. The level of risk for these women is best determined by obtaining a detailed family history and making use of standardized risk assessment tools.
Women who do not have a family history of either breast or ovarian cancer and are unlikely to test positive for the mutations should not be referred for testing, the Task Force emphasized, noting that there are potential harms involved in genetic testing, including false-positive test results. The Task Force does recommend that, starting at age 40, all women should be screened for breast cancer using mammography. This recommendation can be found at at Screening for Breast Cancer.
Testing entails risks. A woman who tests positive for BRCA1 and BRCA2 gene mutations may choose to undergo a procedure such as a preventive mastectomy or oophorectomy-removal of the breast or ovaries-which might be unnecessary if a given mutation would not lead to cancer. Women who test positive for genetic mutations may also be vulnerable to job or insurance discrimination. Federal and state laws provide a degree of protection against discrimination on the basis of genetic information, but concerns persist. In addition, the cost of DNA testing for BRCA mutations can range from several hundred to several thousand dollars, and insurance policies vary regarding coverage of genetic testing.
For those women whose specific family history puts them at risk for genetic mutations and possibly cancer, counseling and BRCA testing may offer significant benefits. "A woman who gains an understanding of the risk she faces may feel less anxious and have a sense of better control of her future," said Task Force Chair Ned Calonge, M.D., who is also Chief Medical Officer and State Epidemiologist for the Colorado Department of Public Health and Information. "If the DNA test result is positive, the patient and her physician should take a shared decision making approach in deciding which preventive measures are appropriate."
The Task Force found evidence in the scientific literature that women with BRCA1 and BRCA2 mutations can reduce their risk of developing breast or ovarian cancer by mastectomy or oophorectomy. Women may also choose to undergo intensive screening by frequent clinical breast examinations and mammography or preventive chemotherapy, but the benefits remain uncertain.
The Task Force, sponsored by the Agency for Healthcare Research and Quality, is the leading independent panel of private-sector experts in prevention and primary care and conducts rigorous, impartial assessments of the scientific evidence for a broad range of preventive services. Its recommendations are considered the gold standard for clinical preventive services.
The Task Force based its conclusions on a report from a research team led by Heidi D. Nelson, M.D., M.P.H., at the Evidence-based Practice Center at Oregon Health & Science University in Portland.
The Task Force uses letters to rate its recommendations according to the strength of the evidence it has found and the amount of net benefit (the size of the benefits minus the harms) a particular preventive service offers. Possible grades are "A" (strongly recommends), "B" (recommends), "C" (no recommendation for or against), "D" (recommends against), or "I" (insufficient evidence to recommend for or against). The Task Force recommends against routine referral for genetic counseling or BRCA testing for women whose family history does not indicate an elevated risk as defined in the recommendation and accompanying review (a "D" recommendation). The Task Force does recommend that women whose family history indicates an increased likelihood of harmful BRCA1 and BRCA2 mutations be referred for genetic counseling and evaluation for BRCA testing (a "B" recommendation).
The recommendations and supporting materials are available at Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility.
Last Updated: August 18, 2016