Underdiagnosis of Hereditary Breast Cancer: Are Genetic Testing Guidelines a Tool or an Obstacle?

Beitsch PD1, Whitworth PW2, Hughes K3, Patel R4, Rosen B5, Compagnoni G5, Baron P6, Simmons R7, Smith LA8, Grady I9, Kinney M10, Coomer C11, Barbosa K12, Holmes DR13, Brown E14, Gold L14, Clark P15, Riley L16, Lyons S17, Ruiz A18, Kahn S19, MacDonald H19, Curcio L20, Hardwick MK21, Yang S22, Esplin ED22, Nussbaum RL22.

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Abstract

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.