Germline BRCA1/2 mutations and severe haematological toxicities in patients with breast cancer treated with neoadjuvant chemotherapy.
Adult
Anthracyclines
/ adverse effects
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
BRCA1 Protein
/ genetics
BRCA2 Protein
/ genetics
Carboplatin
/ adverse effects
Chemotherapy, Adjuvant
/ adverse effects
Chemotherapy-Induced Febrile Neutropenia
/ etiology
Cyclophosphamide
/ adverse effects
Female
Germ-Line Mutation
Germany
Hematologic Diseases
/ chemically induced
Humans
Middle Aged
Neoadjuvant Therapy
/ adverse effects
Randomized Controlled Trials as Topic
Risk Assessment
Risk Factors
Taxoids
/ adverse effects
Thrombocytopenia
/ chemically induced
Treatment Outcome
Triple Negative Breast Neoplasms
/ drug therapy
Carboplatin
Hematological toxicities
Neoadjuvant chemotherapy
Neutropenia
Taxanes
gBRCA1/2 mutation
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
01
10
2020
revised:
02
12
2020
accepted:
04
12
2020
pubmed:
11
1
2021
medline:
21
9
2021
entrez:
10
1
2021
Statut:
ppublish
Résumé
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.
Sections du résumé
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.
Identifiants
pubmed: 33423006
pii: S0959-8049(20)31421-0
doi: 10.1016/j.ejca.2020.12.007
pii:
doi:
Substances chimiques
Anthracyclines
0
BRCA1 Protein
0
BRCA1 protein, human
0
BRCA2 Protein
0
BRCA2 protein, human
0
Taxoids
0
Cyclophosphamide
8N3DW7272P
Carboplatin
BG3F62OND5
Types de publication
Comparative Study
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
44-52Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest statement The authors declare the following conflicts of interest: A.S. reports receiving grants from Celgene, Roche, AbbVie; personal fees from Roche, AstraZeneca, Celgene, Roche, Pfizer, Novartis, MSD, Tesaro, Lilly, and others from Roche, outside the submitted work; C.H. reports receiving personal fees from Roche, Novartis, Lilliy, MSD, Astra Zeneca, and Pfizer; C.J. reports personal fees from Roche, AsraZeneca, Celgene, Pfizer, Novartis, and Amgen; F.J.C. reports receiving personal fees from AstraZeneca; receiving grants from GRAIL, others from Qiagen and Ambry Genetics, outside the submitted work; H.T. reports receiving personal fees from Novartis, Pfizer, AstraZeneca, Roche, Eisai, and Lilly, outside the submitted work; J.H. reports receiving grants and personal fees from Novartis, personal fees from Lilly, Astra Zeneca, Eisai, MSD, and Abbvie, personal fees and other from Pfizer and Roche, other from Daichii; receiving grants, personal fees and other from Celgene; receiving grants and personal fees from Hexal, outside the submitted work; J.U.B. reports receiving personal fees from AMGEN, ASTRA Zeneca, Novartis, Pfizer, Roche, SonoScape, and Sysmex, outside the submitted work; K.L. reports personal fees and non-financial support from Roche, Lilly, personal fees from Novartis and Genomic Health, outside the submitted work; K.R. reports personal fees from AstraZeneca, Tesaro and Pfizer, outside the submitted work; M.U. reports personal fees and non-financial support from Abbvie, Amgen GmbH, Eisai GmbH, Daiji Sankyo, Celgene GmbH, MSD Merck, Mundipharma, Roche Pharma AG, Odonate, TEVA Pharmaceuticals Ind Ltd., Sanofi Aventis Deutschland GmbH, Pfizer GmbH, Astra Zeneca and Lilly Int., Novartis, Clovis Oncology, and Myriad Genetics; personal fees from BMS, Lilly Deutschland, PUMA Biotechnology, Pierre Fabre, outside the submitted work; P.A.F. reports receiving personal fees from Novartis, Lilly, Pierre Fabre, and Seattle Genetics, Roche, Pfizer, Daiichi-Sankyo, Astra Zeneca, Eisai, Merck Sharp & Dohme; grants from Biontech, Cepheid. R.S. reports receiving grants from Cologne Furtune; S.L. reports receiving grants and other from AstraZeneca, Daiichi-Sankyo, Roche, Pfizer, Novartis, Abbvie, Amgen and Celgene during the conduct of the study; grants and non-financial support from Immunomedics; other from Seattle Genetics, PriME/Medscape, Lilly, Samsung, Eirgenix, BMS, Puma, MSD; personal fees from Chugai; grants from Teva and Vifor; outside the submitted work; In addition, S.L. has a patent EP14153692.0 pending. T.L. reports non-financial support from Pharma Mar, Celgene and Daiichi-Sankyo; personal fees and non-financial support from MSD, Pfizer, Roche, Clovis; personal fees from Amgen, Novartis, Teva, Tesaro, outside the submitted work; V.M. reports speaker honoraria from Amgen, Astra Zeneca, Celgene, Roche, TEVA, and consultancy honoraria from Roche, Amgen, Tesaro and Myelo Therapeutic; No other potential conflict of interest relevant to this article was reported.