Screening women who have a predisposition to breast or ovarian cancer for risk-associated genes other than BRCA1 and 2 provides clinically valuable information, according to a study that was published in the August 2015 issue of JAMA Oncology.1

The study showed that these tests may identify 40% to 50% more individuals with hereditary cancer gene mutations than testing for BRCA1/2 alone.

Multigene panel testing is becoming more common for patients who are predisposed to Hereditary Breast and Ovarian Cancer Syndrome (HBOC). But the rapid clinical introduction of such tests has raised concerns regarding the lack of consensus management guidelines for low- to moderate-risk genes, which account for many of the genes tested.

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Leif Ellisen, MD, PhD, of Massachusetts General Hospital (MGH) Cancer Center and Harvard Medical School, in Boston, MA, led a team of researchers to determine the frequency with which multigene panel testing would identify mutations that warrant management changes in patients who lacked BRCA1/2 mutations.

“We showed that identifying individuals with mutations in these genes is likely to change management for them and close family members,” said Dr. Ellisen in an interview with Cancer Therapy Advisor.

“The management changes involved increased cancer screening or in some cases preventive surgery. In many cases, finding a gene mutation prompted a recommendation for testing of additional family members.”

A total of 1,046 women who were referred for genetic counseling and/or HBOC evaluation and lacked BRCA1/2 mutations were enrolled at three academic medical centers: MGH Cancer Center, Stanford University School of Medicine, and Beth Israel Deaconess Medical Center (BIDMC) between 2001 and 2014.

Patients were tested at Stanford and MGH with the 29-gene Hereditary Cancer Syndromes test (n = 669) and at BIDMC with the 25-gene MyRisk test (n = 377).

The researchers found that 3.8% (n=40) of patients who were negative for BRCA1/2 mutation had risk-associated mutations in other hereditary cancer predisposition genes. In 63% of those patients, the mutant gene was associated with low to moderate HBOC risk. In 20% the mutations were found in genes associated with increased ovarian cancer risk.

Researchers enrolled an additional 23 patients who had non-BRCA1/2 mutations and included them in subsequent analyses. Of the 63 patients with risk-associated mutations, 92.1% had personal or family histories associated with the mutant gene.

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“Many of our patients are worried about their risk of future cancers for themselves and their families,” said Dr. Ellisen.

“Identifying a means to quantify this risk more accurately will allow oncologists to make more accurate and hopefully more effective recommendations for future screening and prevention measures for patients and their families.”