Breast Cancer and Genetic Testing in Routine Clinical Practice: Why, When and For Whom?

Pathogenic variants of the tumor suppressor genes and are responsible for the majority of hereditary breast cancers; they are also becoming increasingly important to identify whether patients are suitable for targeted therapy with poly ADP-ribose polymerase inhibitors (PARPi). Patients with HER2-negative breast cancer and germline mutations can benefit significantly from PARPi therapy, and the findings of the OlympiAD and the EMBRACA phase III clinical trials for regulatory approval were recently expanded by the addition of the most recent OlympiA data on the treatment of patients with early disease and a high risk of recurrence. This means that germline testing to plan patient therapy is now also relevant for patients with early breast cancer and therefore has a direct impact on survival. Healthcare research data shows, however, that testing rates are strongly affected by familial history, cancer subtype (particularly triple-negative subtypes), and patient age at onset of disease (especially with regards to younger patients with breast cancer), despite the existing clear recommendations for germline testing to identify whether PARPi therapy is indicated. This article presents the clinical implications of identifying germline mutations in patients with breast cancer, the current recommendations on molecular diagnostics, and their implementation in practice. The treatment of patients with breast cancer has progressed greatly in recent years and now offers individual treatment concepts which can only be implemented after the targeted identification of individual parameters. As detection of a germline mutation is essential for planning individual therapy, where indicated, testing should be arranged as early as possible. It is the only way of identifying patients suitable for PARPi therapy and ensuring they receive the best possible treatment. This also applies to patients with a negative familial history, HR-positive disease, or who are older at onset of disease.