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

Autor: Valentina Nekljudova, Christian Jackisch, Kerstin Rhiem, Jenny Furlanetto, Volker Möbus, Rita K. Schmutzler, Jens Huober, Jens Uwe Blohmer, Peter Klare, Bianca Lederer, Christoph Salat, Kristina Lübbe, Theresa Link, Fergus J. Couch, Eric Hahnen, Peter A. Fasching, Claus Hanusch, Ingo Bauerfeind, Michael Untch, Sibylle Loibl, Dirk Michael Zahm, Hans Tesch, Bernd Gerber, Andreas Schneeweiss
Rok vydání: 2021
Předmět:
Adult
0301 basic medicine
Cancer Research
medicine.medical_specialty
Cyclophosphamide
medicine.medical_treatment
Triple Negative Breast Neoplasms
Neutropenia
Risk Assessment
Gastroenterology
Carboplatin
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Breast cancer
Risk Factors
Germany
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
Humans
Medicine
Anthracyclines
Chemotherapy-Induced Febrile Neutropenia
Germ-Line Mutation
Randomized Controlled Trials as Topic
BRCA2 Protein
Chemotherapy
Taxane
BRCA1 Protein
business.industry
Odds ratio
Middle Aged
medicine.disease
Hematologic Diseases
Thrombocytopenia
Neoadjuvant Therapy
Confidence interval
Treatment Outcome
030104 developmental biology
Oncology
chemistry
Chemotherapy
Adjuvant
030220 oncology & carcinogenesis
Female
Taxoids
business
medicine.drug
Zdroj: European Journal of Cancer. 145:44-52
ISSN: 0959-8049
DOI: 10.1016/j.ejca.2020.12.007
Popis: 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 0.001). No difference was seen under cyclophosphamide or platinum-containing chemotherapies.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.
Databáze: OpenAIRE
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