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

Abstract

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.

Universal Germline Genetic Testing for Hereditary Cancer Syndromes in Patients With Solid Tumor Cancer

“…The recent prospective, multisite Interrogating Cancer Etiology using Proactive genetic Testing (INTERCEPT) study found that clinicians caring for 42 (28.2%) of 149 patients with high-penetrance PGVs documented modifications to treatment and medical management as a result of the findings. 2 These findings are also supported by other studies that have explored individual cancer types more deeply, including breast, 4 , 50 , 59 , 61 , 62 , 70 colorectal, 63 , 65 pancreatic, 19 gastrointestinal, 20 prostate, 71 and other urogenital cancers. 27 , 28 , 68 …”

Global Increase in Breast Cancer Incidence: Risk Factors and Preventive Measures

“…Genetic testing, supported by advancement in genetic sequencing techniques and bioinformatics tools, allows the efficient detection of germline mutations in breast cancer patients. Genetic testing in breast cancer has substantial implications for cancer prevention, early detection, and treatment for patients and their relatives ( Table 2 ) [ 149 ]. Since the last three decades, the germline genetic testing for inherited breast cancer risk prediction has evolved substantially [ 150 ].…”

“…In 2019, the American Society of Breast Surgeons (ASBrS) proposed germline genetic testing for all breast cancer patients to increase the identification of pathological variant carriers [ 168 ]. Over the guidelines of the NCCN (National Comprehensive Cancer Network) and ASBrS, a Mayo Clinic study in 2020 proposed a hybrid approach for germ genetic testing for all diagnosed breast cancer patients with 65 years age using the NCCN criteria for older patients [ 149 ]. Keeping ≤60 or ≤65 years of age for universal testing has detected more pathological variants (11.9% and 15.7% respectively) in comparison with using the NCCN criteria [ 169 ].…”

Germline Genetic Testing for Women With Breast Cancer: Shifting the Paradigm From Whom to Test to Whom NOT to Test

“…A subsequent analysis demonstrated that by lowering the age at diagnosis for universal testing to 60 years, results were essentially identical but an additional 10% of patients were spared genetic testing. 22 In the article that accompanies this editorial, Boddicker et al 23 provide data that support genetic testing for women diagnosed with early-stage TNBC at any age. They found that the frequency of BRCA1/2 or PALB2 mutations in women with TNBC diagnosed after age 65 years is 3.0%, using population-based studies within the CAnceR RIsk Estimates Related to Susceptibility (CARRIERS) consortium.…”