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

  • Epidemiology
  • Published:
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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.

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Acknowledgements

We thank all the patients who agreed to participate to this study. We thank Dr A. Hugli, Dr M. Forni, Dr B. Exquis, Dr C. De Pree, Dr C. Irle, Dr L. Waelchli and Prof. A.-P. Sappino for providing clinical data. We thank Mrs L. Zulianello for the iconographic support.

Funding

A. F. received a Grant from the Fondation Henriette Meyer.

Author information

Authors and Affiliations

  1. Department of Oncology, Hôpitaux Universitaires de Genève, 4 Rue Gabrielle Perret-Gentil, 1205, Geneva, Switzerland

    Alex Friedlaender, Aurélie Vuilleumier, Valeria Viassolo, Alexandre Bodmer, Pierre O. Chappuis & S. Intidhar Labidi-Galy

  2. Department of Genetic Medicine, Laboratory and Clinical Pathology, Hôpitaux Universitaires de Genève, 4 Rue Gabrielle Perret-Gentil, 1205, Geneva, Switzerland

    Aurélie Ayme, Isabelle Gauchat-Bouchardy & Pierre O. Chappuis

  3. Department of Medical Oncology, Centre Léon Bérard, 8 Rue Laennec, 69008, Lyon, France

    Solène De Talhouet & Olivier Tredan

  4. Infections and Cancer Epidemiology Group, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69008, Lyon, France

    Jean-Damien Combes

  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

    Julien Peron

  6. UMR CNRS 5558, Université Lyon 1, Lyon, France

    Julien Peron

  7. Division of Molecular Genetics, Hospices Civils de Lyon, Groupe Hospitalier Edouard Herriot, 5 Place d’Arsonval, 69003, Lyon, France

    Sophie Giraud & Adrien Buisson

  8. Unit of Prevention and Genetic Epidemiology, UMR CNRS 5558, Centre Léon Bérard, 8 Rue Laennec, 69008, Lyon, France

    Valerie Bonadona

  9. Department of Internal Medecine Specialities, Faculty of Medecine, Université de Genève, Rue Michel Servet 1, 1206, Geneva, Switzerland

    S. Intidhar Labidi-Galy

Authors
  1. Alex Friedlaender
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  2. Aurélie Vuilleumier
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  3. Valeria Viassolo
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  4. Aurélie Ayme
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  7. Julien Peron
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  8. Alexandre Bodmer
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  9. Sophie Giraud
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  10. Adrien Buisson
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  12. Isabelle Gauchat-Bouchardy
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  13. Olivier Tredan
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  14. Pierre O. Chappuis
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  15. S. Intidhar Labidi-Galy
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Corresponding author

Correspondence to S. Intidhar Labidi-Galy.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study complies with the current laws in Switzerland and France.

Informed consent

Informed consent was obtained from all alive participants included in the study in Geneva. For this type of study, formal consent is not required.

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Friedlaender, A., Vuilleumier, A., Viassolo, V. et al. BRCA1/BRCA2 germline mutations and chemotherapy-related hematological toxicity in breast cancer patients. Breast Cancer Res Treat 174, 775–783 (2019). https://doi.org/10.1007/s10549-018-05127-2

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  • DOI: https://doi.org/10.1007/s10549-018-05127-2

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