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Breast Cancer Res Treat. 2019 Apr;174(3):775-783. doi: 10.1007/s10549-018-05127-2. Epub 2019 Jan 11.

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

Author information

1
Department of Oncology, Hôpitaux Universitaires de Genève, 4 Rue Gabrielle Perret-Gentil, 1205, Geneva, Switzerland.
2
Department of Genetic Medicine, Laboratory and Clinical Pathology, Hôpitaux Universitaires de Genève, 4 Rue Gabrielle Perret-Gentil, 1205, Geneva, Switzerland.
3
Department of Medical Oncology, Centre Léon Bérard, 8 Rue Laennec, 69008, Lyon, France.
4
Infections and Cancer Epidemiology Group, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69008, Lyon, France.
5
Departement of Medical Oncology, Institut de Cancérologie des Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, 165 Chemin du Grand Revoyet, 69310, Pierre-Bénite, France.
6
UMR CNRS 5558, Université Lyon 1, Lyon, France.
7
Division of Molecular Genetics, Hospices Civils de Lyon, Groupe Hospitalier Edouard Herriot, 5 Place d'Arsonval, 69003, Lyon, France.
8
Unit of Prevention and Genetic Epidemiology, UMR CNRS 5558, Centre Léon Bérard, 8 Rue Laennec, 69008, Lyon, France.
9
Department of Oncology, Hôpitaux Universitaires de Genève, 4 Rue Gabrielle Perret-Gentil, 1205, Geneva, Switzerland. intidhar.labidi-galy@hcuge.ch.
10
Department of Internal Medecine Specialities, Faculty of Medecine, Université de Genève, Rue Michel Servet 1, 1206, Geneva, Switzerland. intidhar.labidi-galy@hcuge.ch.

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.

KEYWORDS:

BRCA mutation; Breast cancer; Chemotherapy; Febrile neutropenia; Haploinsufficiency; Toxicity

PMID:
30635808
DOI:
10.1007/s10549-018-05127-2

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