Underdiagnosis of Hereditary Breast Cancer: Are Genetic Testing Guidelines a Tool or an Obstacle?
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
PURPOSE: An estimated 10% of breast and ovarian cancers result from hereditary causes. Current testing guidelines for germ line susceptibility genes in patients with breast carcinoma were developed to identify carriers of BRCA1/ 2 variants and have evolved in the panel-testing era. We evaluated the capability of the National Comprehensive Cancer Network (NCCN) guidelines to identify patients with breast cancer with pathogenic variants in expanded panel testing.
METHODS: An institutional review board-approved multicenter prospective registry was initiated with 20 community and academic sites experienced in cancer genetic testing and counseling. Eligibility criteria included patients with a previously or newly diagnosed breast cancer who had not undergone either single- or multigene testing. Consecutive patients 18 to 90 years of age were consented and underwent an 80-gene panel test. Health Insurance Portability and Accountability Act-compliant electronic case report forms collected information on patient demographics, diagnoses, phenotypes, and test results.
RESULTS: More than 1,000 patients were enrolled, and data records for 959 patients were analyzed; 49.95% met NCCN criteria, and 50.05% did not. Overall, 8.65% of patients had a pathogenic/likely pathogenic (P/LP) variant. Of patients who met NCCN guidelines with test results, 9.39% had a P/LP variant. Of patients who did not meet guidelines, 7.9% had a P/LP variant. The difference in positive results between these groups was not statistically significant (Fisher's exact test P = .4241).
CONCLUSION: Our results indicate that nearly half of patients with breast cancer with a P/LP variant with clinically actionable and/or management guidelines in development are missed by current testing guidelines. We recommend that all patients with a diagnosis of breast cancer undergo expanded panel testing.
Women & Children
Beitsch, Peter D; Whitworth, Pat W; Hughes, Kevin; Patel, Rakesh; Rosen, Barry; Compagnoni, Gia; Baron, Paul; Simmons, Rache; Smith, Linda Ann; Grady, Ian; Kinney, Michael; Coomer, Cynara; Barbosa, Karen; Holmes, Dennis R; Brown, Eric; Gold, Linsey; Clark, Patricia; Riley, Lee; Lyons, Samuel; Ruiz, Antonio; Kahn, Sadia; MacDonald, Heather; Curcio, Lisa; Hardwick, Mary Kay; Yang, Shan; Esplin, Ed D; and Nussbaum, Robert L, "Underdiagnosis of Hereditary Breast Cancer: Are Genetic Testing Guidelines a Tool or an Obstacle?" (2018). Articles, Abstracts, and Reports. 986.