Germline genetic testing in breast cancer: Rationale for the testing of all women diagnosed by the age of 60 years and for risk‐based testing of those older than 60 years

• Published in: Cancer Vol. 127; no. 6; pp. 828 - 833
• Main Authors: Desai, Neelam V., Yadav, Siddhartha, Batalini, Felipe, Couch, Fergus J., Tung, Nadine M.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 15.03.2021
• Subjects: Age; American Society of Breast Surgeons; BRCA1/2; Breast cancer; Criteria; Genetic screening; Genetic testing; genetic testing criteria; germline genetic testing; National Comprehensive Cancer Network (NCCN); Oncology; genetic testing criteria; American Society of Breast Surgeons; BRCA1/2; germline genetic testing; breast cancer; National Comprehensive Cancer Network (NCCN)
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.33305

Approximately 5% to 10% of women diagnosed with breast cancer will have a pathogenic variant (PV) in a hereditary cancer susceptibility gene, and this has significant implications for the management of these patients and their relatives. Despite the benefits of genetic testing, many eligible patients with breast cancer never undergo testing because of various barriers, including complicated testing criteria such as those from the National Comprehensive Cancer Network (NCCN). In 2019, the American Society of Breast Surgeons (ASBrS) proposed germline genetic testing for all patients with breast cancer to increase the identification of PV carriers. In 2020, a Mayo Clinic study highlighted the limitations of these 2 genetic testing guidelines (NCCN and ASBrS) and proposed a hybrid approach of testing all women diagnosed with breast cancer by the age of 65 years and using NCCN criteria for older patients. This commentary presents an updated analysis of the Mayo Clinic data and discusses the rationale for using the age of 60 years rather than 65 years as the cutoff for this hybrid approach. Using an age at diagnosis of ≤60 or ≤65 years for the universal testing of patients with breast cancer detected more PVs (11.9% [16 of 134] and 15.7% [21 of 134], respectively) in comparison with using the NCCN criteria. Lowering the age for universal testing from 65 to 60 years maintained the sensitivity of detecting a PV at >90% while sparing testing for an additional 10% of women. Compared with the testing of all patients, the hybrid approach would allow 31% of all women with breast cancer to forgo testing and result in fewer variants of uncertain significance identified and, therefore, would decrease the chance of harm from misinterpretation of these variants. The identification of pathogenic variants in high‐risk breast cancer genes has a significant impact on the management of patients with breast cancer and their relatives, yet many women do not receive genetic testing because of various barriers, with one of the major reasons being complex genetic testing criteria. Testing every single patient with breast cancer is not cost‐effective and has the potential for harm through the mismanagement of benign or ambiguous genetic testing results. This commentary argues that a hybrid approach of testing all patients below a certain age threshold while restricting testing on the basis of guidelines for an older population is a better approach.