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

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. Patients from German Breast Group (GBG) and Arbeitsgemeinschaft Gynäkologische Onkologie-breast group s...

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Published in:European journal of cancer (1990) 2021-03, Vol.145, p.44-52
Main Authors: Furlanetto, Jenny, Möbus, Volker, Schneeweiss, Andreas, Rhiem, Kerstin, Tesch, Hans, Blohmer, Jens-Uwe, Lübbe, Kristina, Untch, Michael, Salat, Christoph, Huober, Jens, Klare, Peter, Schmutzler, Rita, Couch, Fergus J., Lederer, Bianca, Gerber, Bernd, Zahm, Dirk-Michael, Bauerfeind, Ingo, Nekljudova, Valentina, Hanusch, Claus, Jackisch, Christian, Link, Theresa, Hahnen, Eric, Loibl, Sibylle, Fasching, Peter A.
Format: Article
Language:English
Subjects:
Anthracycline
BRCA1 protein
BRCA2 protein
Breast cancer
Carboplatin
Chemotherapy
Colony-stimulating factor
Confidence intervals
Cyclophosphamide
DNA repair
gBRCA1/2 mutation
Hematological toxicities
Hematology
Leukocytes (granulocytic)
Mutation
Neoadjuvant chemotherapy
Neutropenia
Platinum
Prophylaxis
Regression analysis
Regression models
Risk
Statistical analysis
Taxanes
Thrombocytopenia
Toxicity
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Summary: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. 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. 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 
ISSN:0959-8049
1879-0852
DOI:10.1016/j.ejca.2020.12.007