The U.S. Preventive Services Task Force (USPSTF) has broadened its criteria for BRCA cancer susceptibility gene testing in women.
Citing moderate benefit and small-to-moderate risk, the USPSTF now recommends that primary care clinicians assess women with either a personal or family history of breast or ovarian cancers as well as women with Ashkenazi Jewish ancestry for their risk of BRCA1/2 mutations — a “B” rating. They recommend a three-step process: a brief risk assessment with a validated tool, referral to genetic counseling if positive, and then BRCA1/2 mutation testing if indicated.
Their final recommendation statement and evidence report backing it were published in JAMA, and expand upon the Task Force’s 2013 guidance, which had recommended risk assessment, genetic counseling, and BRCA testing only in women with a family history of breast or ovarian cancers.
USPSTF continues to recommend against routine risk assessment for women with nothing to suggest likelihood of a positive test result — those with no personal or family history of BRCA-related cancers or ancestry associated with BRCA mutations — giving it a “D” rating.
“When we have a preventive service that can lead to treatments that can save lives, we get very excited about those, and those are our most important recommendations in many respects,” USPSTF member Carol Mangione, MD, MSPH, of the University of California Los Angeles, said in an audio interview that accompanied the publication. “BRCA1 and BRCA2 mutations are important to detect because they really significantly increase the risk for breast or ovarian cancer.”
By the age of 70, these mutations are estimated to increase breast cancer risk by 45% to 65%. For ovarian, fallopian, or peritoneal cancers, BRCA1 mutations increase the risk by 39% while BRCA2 mutations increase the risk by 10% to 17%.
BRCA mutations are present in about 0.2% to 0.3% of the general population, but their prevalence in women of Ashkenazi Jewish descent is tenfold.
“Because that rate is higher in the population of Ashkenazi Jewish women, the recommendation is that they be referred for consideration of genetic testing,” Mangione said.
Cancer-free women with a personal history of a BRCA-related cancer are also now eligible for risk assessment screening under the new guidance.
“This is a big change,” said Mangione.
Notably, the Task Force did not recommend multigene panel testing, omitting other genes linked to increased cancer risk, and instead focused on BRCA1/2 mutations specifically, citing the available evidence on and prevalence of these mutations, and their clinical actionability.
“The lack of recommendation for the use of multigene panels will need to continue to be evaluated as studies have demonstrated the use of multigene panels results in identifying more clinically actionable mutations,” Kristen D. Whitaker, MD, of the clinical genetics department at Fox Chase Cancer Center in Philadelphia, told MedPage Today via email. “In the case of breast cancer predisposition genes, their identification is important as the presence of such mutations could change the clinical management of the woman.”
USPSTF also stopped short of endorsing any specific available risk assessment tools, and instead highlighted the evidence for various “accurate” options. With sensitivity estimates ranging from 77% to 100%, these include: the Ontario Family History Assessment Tool, Manchester Scoring System, Referral Screening Tool, Pedigree Assessment Tool, 7-Question Family History Screening Tool, and the International Breast Cancer Intervention Study instrument (or Tyrer-Cuzick).
“If a patient is positive on those … we recommend genetic counseling, because patients need to have their family tree looked at and need to have a comprehensive discussion about the pros and cons of testing in their specific situation,” explained Mangione.
Read the full article here: https://www.medpagetoday.com/genetics/genetictesting/81709
