Translational Relevance
tumor, germline or somatic BRCA
TUMOR, TRIPLE NEGATIVE BREAST CANCER
The standard systemic therapy of advanced Triple Negative Breast Cancer is cytotoxic chemotherapy, antibody-drug conjugates and immunotherapy (in those with PDL-1 positive tumor). Despite more recent developments, the median overall survival of such patients is 2 years. PARP inhibitors are indicated in the 10–15% of patients with germline or somatic BRCA mutations. Cohort E of the plasmaMATCH Trial found that when a PARP inhibitor (Olaparib) was combined with an ATR inhibitor (Celerasertib), responses were seen both in patients with BRCA mutations and in those without. Patients with pathogenic mutations in other homologous recombination repair genes and low RAD51 foci were amongst responders. This means that patients without BRCA mutations, identifiable by other molecular predictors, may be able to benefit from this therapeutic approach.