BRCA1/BRCA2 germline mutations and chemotherapy-related hematological toxicity in breast cancer patients

Purpose BRCA1 and BRCA2 proteins are central to DNA repair process through homologous recombination. We hypothesize that BRCA1 / BRCA2 mutation carriers may exhibit increased hematological toxicity when receiving genotoxic chemotherapy. Methods We included women with primary breast cancers screened for BRCA1 / BRCA2 germline mutations and treated with (neo)adjuvant chemotherapy in Geneva (Swiss cohort). The primary endpoint was the incidence of febrile neutropenia following the first chemotherapy cycle (C1). Secondary endpoints were the incidence of grade 3–4 neutropenia, grade 4 neutropenia and hospitalization during C1, G-CSF use and chemotherapy dose reduction during the entire chemotherapy regimen. Long-term toxicities (hematological, cardiac and neuropathy) were assessed in the Swiss cohort and a second cohort of patients from Lyon (French cohort). Results Overall, 221 patients were assessed for acute hematological toxicity, including 23 BRCA1 and 22 BRCA 2 carriers. Following the C1, febrile neutropenia had an incidence of 35% ( p = 0.002), 14% ( p = 0.562) and 10% among BRCA1, BRCA 2 and non-carriers, respectively. Grade 4 neutropenia was found in 57% of BRCA1 ( p