Abstract
Pathogenic variants of the tumor suppressor genes BRCA1 and BRCA2 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 BRCA1/2 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 BRCA1/2 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 BRCA1/2 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 BRCA1/2 germline testing to identify whether PARPi therapy is indicated.
This article presents the clinical implications of identifying BRCA1/2 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 BRCA1/2 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.
Keywords breast cancer -
BRCA1/2 diagnostics - therapy planning - PARP inhibitors - talazoparib - olaparib
