Universität zu Köln

Furlanetto, Jenny, Moebus, Volker, Schneeweiss, Andreas, Rhiem, Kerstin, Tesch, Hans, Blohmer, Jens-Uwe ORCID: 0000-0002-7969-250X, Luebbe, 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 and Fasching, Peter A. (2021). Germline BRCA1/2 mutations and severe haematological toxicities in patients with breast cancer treated with neoadjuvant chemotherapy. Eur. J. Cancer, 145. S. 44 - 53. OXFORD: ELSEVIER SCI LTD. ISSN 1879-0852

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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 Gynakologische 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. (C) 2020 Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Furlanetto, Jenny UNSPECIFIED UNSPECIFIED UNSPECIFIED Moebus, Volker UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneeweiss, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Rhiem, Kerstin UNSPECIFIED UNSPECIFIED UNSPECIFIED Tesch, Hans UNSPECIFIED UNSPECIFIED UNSPECIFIED Blohmer, Jens-Uwe UNSPECIFIED orcid.org/0000-0002-7969-250X UNSPECIFIED Luebbe, Kristina UNSPECIFIED UNSPECIFIED UNSPECIFIED Untch, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Salat, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Huober, Jens UNSPECIFIED UNSPECIFIED UNSPECIFIED Klare, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmutzler, Rita UNSPECIFIED UNSPECIFIED UNSPECIFIED Couch, Fergus J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lederer, Bianca UNSPECIFIED UNSPECIFIED UNSPECIFIED Gerber, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED Zahm, Dirk-Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Bauerfeind, Ingo UNSPECIFIED UNSPECIFIED UNSPECIFIED Nekljudova, Valentina UNSPECIFIED UNSPECIFIED UNSPECIFIED Hanusch, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED Jackisch, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Link, Theresa UNSPECIFIED UNSPECIFIED UNSPECIFIED Hahnen, Eric UNSPECIFIED UNSPECIFIED UNSPECIFIED Loibl, Sibylle UNSPECIFIED UNSPECIFIED UNSPECIFIED Fasching, Peter A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-604968
DOI:	10.1016/j.ejca.2020.12.007
Journal or Publication Title:	Eur. J. Cancer
Volume:	145
Page Range:	S. 44 - 53
Date:	2021
Publisher:	ELSEVIER SCI LTD
Place of Publication:	OXFORD
ISSN:	1879-0852
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/60496