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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 3/2019

01-04-2019 | Breast Cancer | Epidemiology

BRCA1/BRCA2 germline mutations and chemotherapy-related hematological toxicity in breast cancer patients

Authors: Alex Friedlaender, Aurélie Vuilleumier, Valeria Viassolo, Aurélie Ayme, Solène De Talhouet, Jean-Damien Combes, Julien Peron, Alexandre Bodmer, Sophie Giraud, Adrien Buisson, Valerie Bonadona, Isabelle Gauchat-Bouchardy, Olivier Tredan, Pierre O. Chappuis, S. Intidhar Labidi-Galy

Published in: Breast Cancer Research and Treatment | Issue 3/2019

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Abstract

Purpose

BRCA1 and BRCA2 proteins are central to DNA repair process through homologous recombination. We hypothesize that BRCA1/BRCA2 mutation carriers may exhibit increased hematological toxicity when receiving genotoxic chemotherapy.

Methods

We included women with primary breast cancers screened for BRCA1/BRCA2 germline mutations and treated with (neo)adjuvant chemotherapy in Geneva (Swiss cohort). The primary endpoint was the incidence of febrile neutropenia following the first chemotherapy cycle (C1). Secondary endpoints were the incidence of grade 3–4 neutropenia, grade 4 neutropenia and hospitalization during C1, G-CSF use and chemotherapy dose reduction during the entire chemotherapy regimen. Long-term toxicities (hematological, cardiac and neuropathy) were assessed in the Swiss cohort and a second cohort of patients from Lyon (French cohort).

Results

Overall, 221 patients were assessed for acute hematological toxicity, including 23 BRCA1 and 22 BRCA2 carriers. Following the C1, febrile neutropenia had an incidence of 35% (p = 0.002), 14% (p = 0.562) and 10% among BRCA1, BRCA2 and non-carriers, respectively. Grade 4 neutropenia was found in 57% of BRCA1 (p < 0.001), 14% of BRCA2 (p = 0.861) and 18% of non-carriers. G-CSF support was necessary in 86% of BRCA1 (p = 0.005), 64% of BRCA2 (p = 0.285) and 51% of non-carriers. For long-term toxicity analysis, 898 patients were included (167 BRCA1-, 91 BRCA2- and 640 non-carriers). There was no difference between the 3 groups.

Conclusions

BRCA1 germline mutations is associated with greater acute hematological toxicity in breast cancer patients. These observations could have implication for primary prophylaxis with G-CSF.
Appendix
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Metadata
Title
BRCA1/BRCA2 germline mutations and chemotherapy-related hematological toxicity in breast cancer patients
Authors
Alex Friedlaender
Aurélie Vuilleumier
Valeria Viassolo
Aurélie Ayme
Solène De Talhouet
Jean-Damien Combes
Julien Peron
Alexandre Bodmer
Sophie Giraud
Adrien Buisson
Valerie Bonadona
Isabelle Gauchat-Bouchardy
Olivier Tredan
Pierre O. Chappuis
S. Intidhar Labidi-Galy
Publication date
01-04-2019
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2019
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-018-05127-2

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