BRCA gene mutation assessments too low for women, experts say
WASHINGTON — More women should be assessed for harmful mutations in the BRCA1 and BRCA2 genes that can increase risk of certain cancers, according to new recommendations.
Previously, it was recommended for women who have a family history of breast, ovarian, tubal or peritoneal cancer to be assessed for harmful BRCA1 or BRCA2 mutations. That recommendation was last made in 2013 by the US Preventive Services Task Force, a volunteer panel of national experts that makes evidence-based recommendations for the primary care community.
Now the USPSTF is updating its recommendation for this risk assessment to include women who personally have been diagnosed with breast, ovarian or tubal cancer in the past but completed treatment and are considered “cancer-free,” and those who have certain ancestries associated with BRCA1 or BRCA2 mutations, such as being of Ashkenazi Jewish descent.
Women with positive results on the primary care risk assessment are then recommended to receive genetic counseling and possibly genetic testing for the mutations.
Routine risk assessment is not recommended for women whose personal history, family history or ancestry does not suggest the possible presence of harmful BRCA1 or BRCA2 mutations.
“It’s important for women to realize that, even though breast cancer is the second-most common cancer in women, that these mutations are actually pretty rare,” said Dr. Carol Mangione, a primary care physician and a professor of medicine and public health at the University of California, Los Angeles, who is a member of the US Preventive Services Task Force.
In the general population, BRCA1 and BRCA2 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, according to the USPSTF.
“Which is why the second part of the recommendation is important, too, that we recommend against routine risk assessment, counseling and genetic testing for women who don’t have a personal history, family history or ancestry associated with a harmful mutation,” Mangione said.
What the screening process involves
To update its recommendation statement, the USPSTF reviewed an evidence report that included 103 previously published studies on the accuracy of risk assessment tools, outcomes of genetic counseling and testing, and interventions to reduce the risk of BRCA-related cancer.
The updated recommendation notes that for women who are recommended for screening for BRCA1 or BRCA2 mutations, that genetic risk assessment and BRCA mutation testing is a multi-step process, which typically begins with assessing risk at a visit with a primary care doctor.
The risk assessment tool helps first to identify patients with family or personal histories of breast, ovarian, tubal or peritoneal cancer, or ancestry associated with harmful BRCA1 or BRCA2 mutations. That assessment helps to determine whether the patient should then undergo genetic counseling, which can further evaluate risk, followed by genetic testing.
Some women found to have harmful BRCA1 or BRCA2 mutations might then choose to take additional steps to lower their cancer risk, such as undergoing intensive screening, taking risk-reducing medications or undergoing risk-reducing surgeries, the choice famously made by actress and UN Special Envoy Angelina Jolie.
The updated USPSTF recommendation statement clarifies that primary care clinicians should assess women with a personal or family history of breast, ovarian, tubal or peritoneal cancer for possible BRCA1 or BRCA2 mutations, said Dr. Banu Arun, professor of breast medical oncology and co-medical director of the Clinical Cancer Genetics Program at MD Anderson Cancer Center in Houston, who was not involved in the new recommendations.
“If patients fit the initial screening criteria and are referred for genetic counseling and testing is indicated, insurance should cover genetic testing,” Arun said.
“These recommendations also confirm that the use of validated risk screening tools are appropriate to use in the primary care setting.”
Concerns about disparities, genetic testing
The updated USPSTF recommendation on BRCA genetic testing, as well as mammographic screening, “are vulnerable to criticism that breast cancer disparities are inadequately addressed,” according to an editorial that published in the journal JAMA Surgery on Tuesday.
“Disproportionately high breast cancer mortality rates in non-Hispanic black women represent a major public health problem. Addressing this disparity in the context of evidence-based guidelines is inevitably challenging because the highest-level evidence is often insufficient to account for breast cancer outcomes specific to” racial or ethnic minorities, wrote the editorial’s author, Dr. Lisa Newman of New York-Presbyterian/Weill Cornell Medical Center.
The updated recommendation “provides an important service in recommending that primary care clinicians take a proactive stance in assessing risk for breast and ovarian cancer by documenting personal as well as family history of cancer and eliciting information regarding Ashkenazi Jewish ancestry,” Newman wrote.
“However, as with any other guideline, 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.”
Dr. Rachel Yung, of the University of Washington in Seattle, and Dr. Larissa Korde, of the National Cancer Institute, co-authored a separate editorial that published in the journal JAMA Oncology on Tuesday.
The editorial mentioned that clinicians should be cognizant of the growing prevalence of direct-to-consumer genetic testing products and the complexities they may bring.
For instance, the US Food and Drug Administration last year granted marketing authorization to 23andMe for direct-to-consumer testing for three specific mutations in BRCA1 and BRCA2 genes that are most common in people of Ashkenazi Jewish descent.
The prevalence of such a mutation “is estimated to be about 2% for women of Ashkenazi Jewish heritage but only 0.1% in women from other populations. This raises the possibility that a patient for whom comprehensive testing is warranted might be falsely assured by a negative test result and not seek further evaluation, or even that a clinician might wrongly assume that the patient does not require referral,” Yung and Korde wrote in the editorial.
They called for additional BRCA-related cancers to be considered when evaluating a person’s family history and improved access to genetic evaluation in the future.