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

Jenny Furlanetto, Volker Möbus, Andreas Schneeweiss, Kerstin Rhiem, Hans Tesch, Jens Uwe Blohmer, Kristina Lübbe, Michael Untch, Christoph Salat, Jens Huober, Peter Klare, Rita Schmutzler, Fergus J. Couch, Bianca Lederer, Bernd Gerber, Dirk Michael Zahm, Ingo Bauerfeind, Valentina Nekljudova, Claus Hanusch, Christian JackischTheresa Link, Eric Hahnen, Sibylle Loibl, Peter A. Fasching

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)44-52
Number of pages9
JournalEuropean Journal of Cancer
Volume145
DOIs
StatePublished - Mar 2021

Keywords

  • Carboplatin
  • Hematological toxicities
  • Neoadjuvant chemotherapy
  • Neutropenia
  • Taxanes
  • gBRCA1/2 mutation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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