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BRCA mutations and their influence on pathological complete response and prognosis in a clinical cohort of neoadjuvantly treated breast cancer patients

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Abstract

Purpose

BRCA1/2 mutations influence the molecular characteristics and the effects of systemic treatment of breast cancer. This study investigates the impact of germline BRCA1/2 mutations on pathological complete response and prognosis in patients receiving neoadjuvant systemic chemotherapy.

Methods

Breast cancer patients were tested for a BRCA1/2 mutation in clinical routine work and were treated with anthracycline-based or platinum-based neoadjuvant chemotherapy between 1997 and 2015. These patients were identified in the tumor registry of the Breast Center of the University of Erlangen (Germany). Logistic regression and Cox regression analyses were performed to investigate the associations between BRCA1/2 mutation status, pathological complete response, disease-free survival, and overall survival.

Results

Among 355 patients, 59 had a mutation in BRCA1 or in BRCA2 (16.6%), 43 in BRCA1 (12.1%), and 16 in BRCA2 (4.5%). Pathological complete response defined as “ypT0; ypN0” was observed in 54.3% of BRCA1/2 mutation carriers, but only in 22.6% of non-carriers. The adjusted odds ratio was 2.48 (95% CI 1.26–4.91) for BRCA1/2 carriers versus non-carriers. Patients who achieved a pathological complete response had better disease-free survival and overall survival rates compared with those who did not achieve a pathological complete response, regardless of BRCA1/2 mutation status.

Conclusions

BRCA1/2 mutation status leads to better responses to neoadjuvant chemotherapy in breast cancer. Pathological complete response is the main predictor of disease-free survival and overall survival, independently of BRCA1/2 mutation status.

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Acknowledgements

The authors are grateful to Michael Robertson for professional medical editing services.

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University Erlangen–Nuremberg, Erlangen, Germany

    Marius Wunderle, Paul Gass, Lothar Häberle, Vivien M. Flesch, Claudia Rauh, Mayada R. Bani, Carolin C. Hack, Michael G. Schrauder, Sebastian M. Jud, Julius Emons, Michael P. Lux, Matthias W. Beckmann, Peter A. Fasching & Alexander Hein

  2. Institute of Pathology, Erlangen University Hospital, Friedrich Alexander University Erlangen–Nuremberg, Erlangen, Germany

    Ramona Erber & Arndt Hartmann

  3. Institute of Human Genetics, Erlangen University Hospital, Friedrich Alexander University Erlangen–Nuremberg, Erlangen, Germany

    Arif B. Ekici, Juliane Hoyer, Georgia Vasileiou, Cornelia Kraus & Andre Reis

  4. Biostatistics Unit, Department of Gynecology and Obstetrics, Erlangen University Hospital, Friedrich Alexander University Erlangen–Nuremberg, Erlangen, Germany

    Lothar Häberle

  5. Department of Medicine, Division of Hematology and Oncology, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA

    Peter A. Fasching

Authors
  1. Marius Wunderle
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  2. Paul Gass
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  3. Lothar Häberle
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  4. Vivien M. Flesch
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  5. Claudia Rauh
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  6. Mayada R. Bani
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  7. Carolin C. Hack
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  8. Michael G. Schrauder
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  9. Sebastian M. Jud
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  10. Julius Emons
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  11. Ramona Erber
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  12. Arif B. Ekici
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  13. Juliane Hoyer
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  14. Georgia Vasileiou
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  15. Cornelia Kraus
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  16. Andre Reis
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  17. Arndt Hartmann
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  18. Michael P. Lux
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  19. Matthias W. Beckmann
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  20. Peter A. Fasching
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  21. Alexander Hein
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Contributions

MW, AH, PG, and PAF contributed substantially to the acquisition and interpretation of data, to the conception and drafting of the manuscript, and to critical revision. LH performed statistical analyses and contributed to the conception, drafting, and critical revision of the manuscript. The contribution of VMF to this publication was made in partial fulfillment of the requirements for obtaining the degree of Doctor of Medicine; parts of the research published here were used for her doctoral thesis at the Medical Faculty of Friedrich Alexander University Erlangen–Nuremberg (FAU). CR, MRB, CCH, MGS, SMJ, JE, RE, ABE, JH, GV, CK, AR, AH, MPL, MWB, and AH were involved in the acquisition of patient and tumor data and genetic information. All authors have read the manuscript and have given their final approval for publication of this study.

Corresponding author

Correspondence to Peter A. Fasching.

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Conflict of interest

PAF has received honoraria from Amgen, Celgene, Roche, Pfizer, and Novartis. MPL has received honoraria from MSD and AstraZeneca. PG has received honoraria from Novartis and financial support for symposia from Roche, Novartis, and PharmaMar. All other authors declare that they do not have any conflicts of interest.

Ethical approval

This retrospective study and the anonymized scientific use of the data were approved by the Ethics Committee of the Medical Faculty of Friedrich Alexander University Erlangen–Nuremberg.

Informed consent

Informed consent was obtained from each individual participant included in the study.

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Wunderle, M., Gass, P., Häberle, L. et al. BRCA mutations and their influence on pathological complete response and prognosis in a clinical cohort of neoadjuvantly treated breast cancer patients. Breast Cancer Res Treat 171, 85–94 (2018). https://doi.org/10.1007/s10549-018-4797-8

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  • DOI: https://doi.org/10.1007/s10549-018-4797-8

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