Studies Challenge Relevance of Genetic Testing Guidelines for Breast Cancer


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NEW RESEARCH suggests that current genetic testing guidelines for breast cancer are far too restrictive, excluding nearly half of high-risk patients. According to a pair of studies presented at the 2018 American Society of Breast Surgeons (ASBrS) Annual Meeting, women with breast cancer who did not meet genetic testing criteria had pathogenic mutations just as frequently as those who qualified for testing. 

In one study, test results from an 80-gene panel found no statistically significant difference in the number of pathogenic mutations between breast cancer patients who met National Comprehensive Cancer Network® (NCCN®) testing guidelines and those who did not.1 In a separate study of 4,196 Medicare patients referred for suspicion of hereditary breast and ovarian cancers (eg, BRCA1/BRCA2) testing, the rate of pathogenic variants was similar among patients who qualified for testing under Medicare guidelines and those who did not.2 

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“Economically based guidelines for genetic testing of breast cancer patients are anachronistic, miss a significant number of pathogenic variants, and we believe they should be abolished immediately,” said Peter Beitsch, MD, of the TME Breast Care Network, Dallas. “As of right now, there’s no statistically significant difference in the pathogenic mutation rate between people who meet national guidelines like those of the NCCN and people who don’t.” 

Many Pathogenic Mutations Missed 

AS DR. BEITSCH reported at a press briefing in advance of the ASBrS meeting, pathogenic genetic mutations are estimated to occur in 10% to 15% of all breast cancer patients, with BRCA1 or BRCA2 accounting for nearly half of these mutations. However, it is estimated that less than 30% of breast cancer patients harboring a BRCA1 or BRCA2 mutation have been identified, and the percentage is much lower for the approximately 20 other breast cancer–associated genes. 

“Economically based guidelines for genetic testing of breast cancer patients are anachronistic, miss a significant number of pathogenic variants, and we believe they should be abolished immediately.”
— Peter Beitsch, MD

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“Our failure to identify patients with pathogenic or likely pathogenic mutations is multifactorial and includes physician education, insurance road blocks, and most importantly, confusing and restrictive testing guidelines,” Dr. Beitsch noted. 

For this study, Dr. Beitsch and colleagues created a community-based registry to determine the incidence of pathogenic variants in patients with breast cancer who meet and do not meet the 2017 NCCN genetic testing criteria.1 Breast cancer patients who had no prior genetic testing underwent an 80-gene panel test for genetic variants that have a known association to breast and/or other cancers. The study has a target accrual of 1,000 patients, including 500 who meet NCCN testing guidelines and 500 who do not. 

Dr. Beitsch reported findings for the first 713 patients with complete data. Patients who met NCCN testing guidelines criteria had a 10.2% pathogenic/likely pathogenic variant rate (36 of 353), whereas those who did not meet these criteria had an 8.6% pathogenic/likely pathogenic variant rate (31 of 360). According to the authors, more than 42% of patients with cancer-related mutations fell outside NCCN testing criteria and thus may be missed if these guidelines are required for genetic testing. 

Need for Revised Testing Criteria 

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IN THE OTHER study, Jennifer Axilbund, MS, CGC, a certified genetic counselor at Invitae, San Francisco, and colleagues examined 4,196 Medicare patients referred by physicians for genetic testing for BRCA1 or BRCA2 and other breast cancer–related mutations.2 As Ms. Axilbund reported, 3,549 patients (85%) met BRCA1/2 testing guidelines, whereas 647 (15%) did not. 

When results for BRCA1/2 variants alone were considered, researchers found no statistical difference between Medicare qualifiers and nonqualifiers (3.2% vs 1.9%). Similar results were found when testing for other breast cancer–related genes (10.5% vs 9.0%). 

“Testing criteria should be broadened to include unaffected individuals with a positive family history and affected individuals with a less severe presentation.”
— Jennifer Axilbund, MS, CGC

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“Under Medicare criteria, almost half of all patients with actionable gene variants are missed,” said Ms. Axilbund, who stressed that current guidelines for genetic testing are based on historically severe clinical presentations of high-penetrant genes and variants. “These criteria do not adequately reflect evolving genetic knowledge, and they miss patients who should undergo increased cancer screening or potentially receive different systemic therapy. Testing criteria should be broadened to include unaffected individuals with a positive family history and affected individuals with a less severe presentation.” 

Dr. Beitsch strongly emphasized the need for revised testing criteria, noting that economically based guidelines are set up to restrict testing rather than to be inclusive. 

“Probably everybody should be genetically tested, and I think in the near future will be, but we can at least start by breaking down these restrictive, economically based guidelines for breast cancer patients,” Dr. Beitsch observed. 

“When testing was $5,000 per test, I could understand the economic roadblock that was set up, but now that testing costs ~$250, it really makes no sense,” he added. “You’re harming women by not testing them, and the cascade effect of not testing their siblings, their parents, and their children is tremendous.” ■ 

DISCLOSURE: Dr. Beitsch reported no conflicts of interest. Ms. Axilbund and her coauthors are employees and shareholders of Invitae. 

REFERENCES 

1. Beitsch P, Whitworth P, Patel R, et al: Are genetic testing guidelines still relevant? 2018 American Society of Breast Surgeons Annual Meeting. Abstract 402910. Presented May 4, 2018

2. Axilbund J, O’Leary E, Michalski S, et al: HBOC patients who do not meet Medicare criteria for genetic testing have similar rates of clinically actionable findings as those who do meet criteria. 2018 American Society of Breast Surgeons Annual Meeting. Abstract 404340. Presented May 4, 2018


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