Subtypes in BRCA-mutated breast cancer

Abstract

Approximately 3% to 5% of breast cancer patients are BRCA1 or BRCA2 germline mutation carriers. In this study, we correlated the distribution of intrinsic molecular subtypes according to failure pattern in a Danish cohort of BRCA germline–mutated breast cancer patients. Tumor tissues from 425 BRCA germline–mutated breast cancer patients were analyzed by immunohistochemistry for hormone receptor status, proliferation index (Ki-67), and HER2. Surrogate intrinsic molecular subtypes were assigned according to approximated St Gallen criteria. Annual hazard rates (AHR) were calculated for death and local or distant relapse, contralateral breast cancer, new primary cancer other than breast cancer, or death as first event (disease-free event). Luminal A–like subtype was observed with a frequency of 9% and 35% for BRCA1 and BRCA2, respectively, and for both BRCA1 and BRCA2 patients, the luminal B–like subtype was more frequent than the luminal A–like subtype (BRCA1 21% and BRCA2 40% luminal B–like). No events or deaths were observed for luminal A–like subtype during the first 2.5 and 0 to 5 years, respectively. AHRs for luminal B–like tumors were 5.34% (95% confidence interval [CI], 1.49-1.19) and 1.76% (95% CI, 0.36-3.16) for disease-free event and death, respectively, and those for basal-like were 6.58% (95% CI, 2.98-10.18) and 4.54% (95% CI, 2.69-6.40). A substantial proportion of BRCA carriers had luminal A–like subtype, and these were mainly BRCA2 carriers. Luminal A–like subtype was significantly associated with low AHR the first 5 years after surgery. This study warrants further exploration of the impact of the molecular intrinsic subtypes on survival in BRCA-mutated breast cancer patients.