Germline BRCA1/2 mutations and severe haematological toxicities in patients with breast cancer treated with neoadjuvant chemotherapy

Eur J Cancer. 2021 Mar;145:44-52. doi: 10.1016/j.ejca.2020.12.007. Epub 2021 Jan 7.


Background: BRCA1 and BRCA2 play a central role in DNA repair. Therefore, patients harbouring germline (g) BRCA1/2 mutations (m) treated with chemotherapy might be at higher risk of haematological toxicities.

Methods: Patients from German Breast Group (GBG) and Arbeitsgemeinschaft Gynäkologische Onkologie-breast group studies with early triple-negative breast cancer (TNBC) and known gBRCA1/2m status treated with anthracycline-taxane-based neoadjuvant chemotherapy were analysed. Primary objective was the rate of neutropenia grade (G)III-IV in cycle 1 (C1). Secondary objectives included effects on overall and other haematological toxicities GIII-IV in C1, cumulative haematological toxicity across all cycles, relative total dose intensity, and granulocyte-colony stimulating factor prophylaxis. Haematological toxicities under taxanes, carboplatin, and cyclophosphamide were explored.

Results: Two hundred nine of 1171 (17.8%) evaluated patients had gBRCA1/2m. In C1, 37.4% gBRCA1/2m versus 35.7% wild-type patients had neutropenia GIII-IV (P = 0.683). For C1, gBRCA1/2m predicted neither for neutropenia GIII-IV (odds ratio [OR]: 1.26, 95% confidence intervals [CI]: 0.87-1.82, P = 0.226) nor for other haematological toxicities GIII-IV (OR: 0.91, 95% CI: 0.64-1.31, P = 0.625) in multivariable regression models. Analyses of cumulative toxicities across all cycles yielded similar results except thrombocytopaenia GIII-IV, which was increased in gBRCA1m patients. In patients treated with taxanes, the rate of haematological toxicities GIII-IV was higher in gBRCA1/2m compared with wild-type (59.5% versus 43.1%; p < 0.001). No difference was seen under cyclophosphamide or platinum-containing chemotherapies.

Conclusions: gBRCA1/2m was not associated with higher risk of overall severe haematological toxicities in the first cycle or cumulatively across all cycles under standard chemotherapy for TNBC. Under taxane, patients with gBRCA1/2m might have a higher risk of haematological toxicities GIII-IV, requiring further research.

Keywords: Carboplatin; Hematological toxicities; Neoadjuvant chemotherapy; Neutropenia; Taxanes; gBRCA1/2 mutation.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adult
  • Anthracyclines / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Carboplatin / adverse effects
  • Chemotherapy, Adjuvant / adverse effects
  • Chemotherapy-Induced Febrile Neutropenia / etiology
  • Cyclophosphamide / adverse effects
  • Female
  • Germ-Line Mutation*
  • Germany
  • Hematologic Diseases / chemically induced*
  • Hematologic Diseases / diagnosis
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy / adverse effects*
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors
  • Taxoids / adverse effects*
  • Thrombocytopenia / chemically induced
  • Treatment Outcome
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / pathology


  • Anthracyclines
  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Taxoids
  • Cyclophosphamide
  • Carboplatin