Asymptomatic women with a family history of breast, ovarian, tubal, or peritoneal cancers should be screened for potentially increased risk for BRCA mutations, according to a new guideline from the U.S. Preventive Services Task Force.
Those with positive screening results should undergo genetic counseling to determine whether they should be tested for mutations in the breast cancer susceptibility genes BRCA1 and BRCA2, according to the guideline, which was published online Dec. 23 in Annals of Internal Medicine. The guideline applies only to at-risk women who have not been previously diagnosed with BRCA-related cancer and who have no signs or symptoms of the disease.
Dr. Douglas K. Owens
Genetic counseling "increases the accuracy of risk perception; decreases intention for mutation testing among women who are unlikely carriers; and decreases cancer worry, anxiety, and depression," according to the guideline writers. Routine genetic counseling and testing are not recommended for average-risk women.
BRCA1 and BRCA2 mutations occur in 0.2%-0.3% of women in the general population. The risk is higher in certain population subgroups: A meta-analysis showed that the combined prevalence of the mutations was 2.1% in a general population of Ashkenazi Jewish women, the guideline notes.
"Women should have their family history assessed to help make sure that clinicians identify the small number of women with BRCA mutations," Dr. Douglas K. Owens, a member of the U.S. Preventive Services Task Force (USPSTF), said in an interview. He emphasized that "most women would not need or not benefit from BRCA testing; it’s really a small minority."
The task force said that the new guideline reaffirms its 2005 recommendation on BRCA testing, but noted that an update was in order because "the potential benefits and harms of medications for breast cancer risk reduction have been studied for longer follow-up periods, and more information is available about the potential psychological effects of genetic counseling and risk-reducing surgery."
Additionally, family history risk-stratification tools are now available and have been developed and validated for use in primary care settings to guide referrals for BRCA genetic counseling. These include the Ontario Family History Assessment Tool, the Manchester Scoring System, the six-question Referral Screening Tool, the Pedigree Assessment Tool, and a seven-question family history screening instrument known as the FHS-7. These tools, which are all estimated to be more than 85% sensitive, "elicit information about factors associated with increased likelihood of BRCA mutations," wrote the members of the task force, which was chaired by Dr. Virginia A. Moyer, vice president for maintenance of certification and quality at the American Board of Pediatrics.
"The USPSTF recognizes that each risk-assessment tool has limitations, and found insufficient evidence to recommend one tool over another," the task force members wrote.
The guideline does not recommend a specific course of action for women who test positive for BRCA gene mutations. Options for women to consider include "intensive surveillance for breast cancer primarily, consideration of medications to reduce the risk of breast cancer, and either prophylactic mastectomy or prophylactic oophorectomy. If someone is BRCA-positive, the role of the primary care clinician is to have an initial discussion of what the person would like to consider. These would be discussions that might include other kinds of clinicians as well," said Dr. Owens, director of the Center for Primary Care and Outcomes Research at Stanford (Calif.) University.
Before issuing the new guideline, task force members reviewed evidence published in 2004 or later related to risk assessment, genetic counseling, and genetic testing for potentially harmful BRCA mutations in asymptomatic women with a family history of breast or ovarian cancer but no personal history of cancer or known potentially harmful BRCA mutations in their family. They also reviewed interventions aimed at reducing the risk for BRCA-related cancer in women with potentially harmful BRCA mutations.
In its evidence review, the task force concluded that limitations of studies included differences in designs and measures, dissimilar comparison groups, and small sizes. "Risk perception improved after receiving test results, and breast cancer worry and anxiety increased for women with positive results and decreased for others, although results were inconsistent. Studies were limited by high loss to follow-up and differences between comparison groups. Other relevant adverse effects of genetic testing were not studied, including false positive or negative results, genetic discrimination, and insurability."
The task force called for efforts to determine the appropriateness of risk assessment and testing for BRCA mutations in primary care, including research "on access to testing, effectiveness of screening approaches including risk stratification, use of system supports, and patient acceptance and education. Trials comparing types of providers and protocols could address questions about who should perform these services, how they should be done, and what skills are required. The consequences of identifying women as high risk, as well as genetic testing of individuals and their relatives, require more study."