Routine Genetic Testing of Germline Breast Cancer Susceptibility ─ Challenges and Opportunities

Abstract

Information on germline BRCA (g*BRCA*) 1/2 pathogenic or likely pathogenic mutations has predictive value for response to platinating agents and poly(ADP-ribose) polymerase inhibitors (PARPi) and survival outcomes of breast cancer (BC) patients. In the OlympiA trial, the benefits of adjuvant olaparib for high-risk patients with human epidermal growth factor receptor 2 (HER2)-negative BC and g*BRCA* mutations were demonstrated. These results highlight that, in addition to establishing BC risk, determining g*BRCA1/2* status has a broader role in treatment decision-making, particularly for BC patients who may benefit from PARPi. Notably, olaparib is the only PARPi currently approved in Switzerland for treating early high-risk BC patients with g*BRCA1/2* mutations. Rates of germline genetic testing in people with and without cancer are suboptimal in Switzerland and worldwide. Nowadays, despite the favorable OlympiA results, testing criteria for BC remain mostly restricted to patients fulfilling certain high-risk criteria for being mutation carriers, and few studies describe *BRCA* testing in BC patients with characteristics excluded in the OlympiA trial. Many unsolved questions remain, such as the number of patients who could potentially benefit from PARPi, whether to use treatment decision as a testing criterion for screening, and whether universal genetic testing for all BC patients is warranted. This review provides an overview of the rationale for targeting *BRCA1/2*. In addition, unmet needs and opportunities for testing *BRCA1/2* status are discussed, and differences in the testing criteria in existing guidelines are summarized.