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

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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 Gynäkologisch...

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Main Authors: Furlanetto, Jenny (Author) , Möbus, Volker (Author) , Schneeweiss, Andreas (Author) , Rhiem, Kerstin (Author) , Tesch, Hans (Author) , Blohmer, Jens-Uwe (Author) , Lübbe, Kristina (Author) , Untch, Michael (Author) , Salat, Christoph (Author) , Huober, Jens (Author) , Klare, Peter (Author) , Schmutzler, Rita (Author) , Couch, Fergus J. (Author) , Lederer, Bianca (Author) , Gerber, Bernd (Author) , Zahm, Dirk-Michael (Author) , Bauerfeind, Ingo (Author) , Nekljudova, Valentina (Author) , Hanusch, Claus (Author) , Jackisch, Christian (Author) , Link, Theresa (Author) , Hahnen, Eric (Author) , Loibl, Sibylle (Author) , Fasching, Peter A. (Author)
Format: Article (Journal)
Language:English
Published: 7 January 2021
In: European journal of cancer
Year: 2021, Volume: 145, Pages: 44-52
ISSN:1879-0852
DOI:10.1016/j.ejca.2020.12.007
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.ejca.2020.12.007
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0959804920314210
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Author Notes: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 Jackisch, Theresa Link, Eric Hahnen, Sibylle Loibl, Peter A. Fasching
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Summary: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.
Item Description:Gesehen am 21.04.2021
Physical Description:Online Resource
ISSN:1879-0852
DOI:10.1016/j.ejca.2020.12.007

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