In a single-institution study reported in the Journal of Clinical Oncology, Yadav et al found that many women with breast cancer with germline pathogenic genetic variants do not qualify for genetic testing on current National Comprehensive Cancer Network® (NCCN®) hereditary testing criteria. Modification of NCCN criteria to include all women diagnosed at 65 years old or younger was found to improve sensitivity of testing criteria.
Study Details
The study was performed to compare NCCN criteria with the strategy of testing of all women with breast cancer recommended by the American Society of Breast Surgeons. The study included women from the Mayo Clinic Breast Cancer Study prospective registry who were evaluated at Mayo Clinic, Rochester for a diagnosis of first invasive breast cancer or ductal carcinoma in situ between May 2000 and May 2016. The women were evaluated for germline pathogenic variants in nine predisposition genes (ATM, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, and TP53).
“Expansion of NCCN criteria to include all women diagnosed at 65 [or younger] improves the sensitivity of the selection criteria without requiring testing of all women with breast cancer.”— Yadav et al
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Key Findings
Testing of all 3,907 eligible women identified pathogenic variants in the nine genes in 6.2% of patients and in BRCA1 or BRCA2 in 2.7% of patients.
Among the eligible women, 1,872 (47.9%) met NCCN criteria for testing. Compared with 2,035 women not meeting NCCN criteria, those meeting the criteria were more likely to carry a pathogenic variant in the nine genes (9.0% vs 3.5%, P < .001) and in BRCA1/2 (5.0% vs 0.7%, P < .001). The sensitivity of NCCN criteria was 70% for the nine predisposition genes and 87% for BRCA1/2, with a specificity of 53%.
Expansion of the NCCN criteria to include all women diagnosed at age 65 or younger was associated with sensitivity of > 90% for the nine predisposition genes and > 98% for BRCA1/2. The expanded criteria required testing of an additional 31% of women compared with NCCN criteria, with 21% remaining untested, and was associated with a specificity of 22%.
The investigators concluded, “A substantial proportion of women with breast cancer carrying germline pathogenic variants in predisposition genes do not qualify for testing by NCCN criteria. Expansion of NCCN criteria to include all women diagnosed at 65 [or younger] improves the sensitivity of the selection criteria without requiring testing of all women with breast cancer."
Fergus J. Couch, PhD, of the Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Institutes of Health and by the Breast Cancer Research Foundation. For full disclosures of the study authors, visit ascopubs.org.
