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Clinical Study

Survival from breast cancer in women with a BRCA2 mutation by treatment

British Journal of Cancer volume 124, pages 1524–1532 (2021)Cite this article

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A Correction to this article was published on 13 January 2023

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Abstract

Background

The impact of various breast-cancer treatments on patients with a BRCA2 mutation has not been studied. We sought to estimate the impact of bilateral oophorectomy and other treatments on breast cancer-specific survival among patients with a germline BRCA2 mutation.

Methods

We identified 664 women with stage I–III breast cancer and a BRCA2 mutation by combining five different datasets (retrospective and prospective). Subjects were followed for 7.2 years from diagnosis to death from breast cancer. Tumour characteristics and cancer treatments were patient-reported and derived from medical records. Predictors of survival were determined using Cox proportional hazard models, adjusted for other treatments and for prognostic features.

Results

The 10-year breast-cancer survival for ER-positive patients was 78.9% and for ER-negative patients was 82.3% (adjusted HR = 1.23 (95% CI, 0.62–2.45, p = 0.55)). The 10-year breast-cancer survival for women who had a bilateral oophorectomy was 89.1% and for women who did not have an oophorectomy was 59.0% (adjusted HR = 0.45; 95% CI, 0.28–0.72, p = 0.001). The adjusted hazard ratio for chemotherapy was 0.83 (95% CI, 0.65–1.53: p = 0.56).

Conclusions

For women with breast cancer and a germline BRCA2 mutation, positive ER status does not predict superior survival. Oophorectomy is associated with a reduced risk of death from breast cancer and should be considered in the treatment plan.

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Fig. 1: Ten-year breast cancer-specific survival for women with BRCA2 mutations.
Fig. 2: Ten-year breast cancer-specific survival for women with BRCA2 mutations.

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Acknowledgements

Our sincere gratitude for the valuable contributions of the women who participated in this study, without whom this research would not be possible. We would like to acknowledge the following individuals for helping with data collection: Sara Lazzarin, Debora Vicini and Federica Sina.

Other members of the Polish Hereditary Breast Cancer Consortium

Błasińska-Morawiec Maria16, Chosia Maria17, Drosik Kazimierz18, Gozdecka-Grodecka Sylwia19, Goźdź Stanisław20, Grzybowska Ewa21, Jeziorski Arkadiusz22, Karczewska Aldona23, Kordek Radzisław22, Synowiec Agnieszka24, Kozak-Klonowska Beata25, Lamperska Katarzyna26, Lange Dariusz27, Mackiewicz Andrzej19, Mituś Jerzy Władysław28, Niepsuj Stanislas29, Oszurek Oleg17, Gugała Karol30, Morawiec Zbigniew16, Mierzwa Tomasz31, Posmyk Michał32, Ryś Janusz33, Szczylik Cezary34, Uciński Michał17, Urbański Krzysztof35, Waśko Bernard36, Wandzel Piotr37

Other members of the kConFab Follow-Up Study Team

Michael Friedlander38, Sue Anne McLachlan39, Stephanie Nesci40, Sandra Picken40, Sarah O’Connor40, Lucy Stanhope40

Other members of Hereditary Breast Cancer Clinical Study Group

Andrea Eisen41, Kevin Sweet42, Raymond Kim43, William Foulkes44, Pal Moller45, Susan Neuhausen46, Carey Cullinane47, Charis Eng48, Peter Ainsworth49, Fergus Couch50, Christian Singer51, Beth Karlan52, Wendy McKinnon53, Marie Wood53

Author information

Authors and Affiliations

  1. Genomic Medicine, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK

    D. Gareth Evans, Zerin Hyder & Claire Forde

  2. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia

    Kelly-Anne Phillips

  3. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia

    Kelly-Anne Phillips

  4. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia

    Kelly-Anne Phillips & Roger L. Milne

  5. Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia

    Roger L. Milne

  6. Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia

    Roger L. Milne

  7. Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy

    Robert Fruscio

  8. Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland

    Cezary Cybulski, Jacek Gronwald, Jan Lubinski & Tomasz Huzarski

  9. University of Zielona Góra, Zielona Góra, Poland

    Tomasz Huzarski & Steven A. Narod

  10. Women’s College Research Institute, Women’s College Hospital, Toronto, ON, Canada

    Kelly Metcalfe, Ping Sun & Steven A. Narod

  11. Division of Human Genetics, the Ohio State University Medical Center, Comprehensive Cancer Center, Columbus, OH, USA

    Leigha Senter

  12. Division of Clinical Cancer Genomics, Department of Population Sciences, City of Hope, Duarte, CA, USA

    Jeffrey Weitzel

  13. Beth Israel Deaconess Medical Center, Boston, MA, USA

    Nadine Tung

  14. Nancy and James Grosfeld Cancer Genetics Center, Beaumont Cancer Institute, Beaumont Health, Royal Oak, MI, USA

    Dana Zakalik

  15. Manchester Academic Health Science Centre, Department of Medical Oncology, The Christie, Manchester, UK

    Maria Ekholm

  16. Copernicus Memorial Hospital, Lodz, Poland

    Maria Błasińska-Morawiec & Zbigniew Morawiec

  17. Pomeranian Medical University, Szczecin, Poland

    Maria Chosia, Oleg Oszurek & Michał Uciński

  18. Regional Cancer Center, Opole, Poland

    Kazimierz Drosik

  19. Poznan University of Medical Sciences, Poznań, Poland

    Sylwia Gozdecka-Grodecka & Andrzej Mackiewicz

  20. Holycross Cancer Centre, Kielce, Poland

    Stanisław Goźdź

  21. Maria Skłodowska-Curie Institute, Gliwice, Poland

    Ewa Grzybowska

  22. Medical University of Lodz, Lodz, Poland

    Arkadiusz Jeziorski & Radzisław Kordek

  23. University School of Medical Sciences at Great Poland Cancer Center, Poznań, Poland

    Aldona Karczewska

  24. Military Institute of Medicine, Warsaw, Poland

    Agnieszka Synowiec

  25. Holycross Cancer Centre, Kielce, Poland

    Beata Kozak-Klonowska

  26. Greater Poland Cancer Centre, Poznan, Poland

    Katarzyna Lamperska

  27. Maria Sklodowska-Curie Institute-Oncology Center, Gliwice, Poland

    Dariusz Lange

  28. Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Krakow, Poland

    Jerzy Władysław Mituś

  29. M. Skłodowska-Curie Memorial Institute of Oncology, Krakow, Poland

    Stanislas Niepsuj

  30. Regional Oncology Hospital, Olsztyn, Poland

    Karol Gugała

  31. Regional Oncology Hospital, Bydgoszcz, Poland

    Tomasz Mierzwa

  32. Regional Oncology Center, Białystok, Poland

    Michał Posmyk

  33. Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Krakow, Poland

    Janusz Ryś

  34. Military Hospital, Warsaw, Poland

    Cezary Szczylik

  35. Institute of Oncology, Krakow, Poland

    Krzysztof Urbański

  36. Regional Hospital, Rzeszów, Poland

    Bernard Waśko

  37. Regional Hospital Bielsko-Biała, Bielsko-Biała, Poland

    Piotr Wandzel

  38. Prince of Wales Hospital, Randwick, Australia

    Michael Friedlander

  39. St Vincent’s Hospital, Fitzroy, Australia

    Sue Anne McLachlan

  40. Peter MacCallum Cancer Centre, Melbourne, Australia

    Stephanie Nesci, Sandra Picken, Sarah O’Connor & Lucy Stanhope

  41. Sunnybrook Health Sciences Centre, Toronto, Canada

    Andrea Eisen

  42. Ohio State University, Columbus, Ohio, USA

    Kevin Sweet

  43. University Health Network, Toronto, Canada

    Raymond Kim

  44. McGill University, Montreal, Canada

    William Foulkes

  45. Norwegian Radium Hospital, Oslo, Norway

    Pal Moller

  46. City of Hope, Duarte, CA, USA

    Susan Neuhausen

  47. City of Hope National Medical Center, Duarte, CA, USA

    Carey Cullinane

  48. Cleveland Clinic, Cleveland, Ohio, USA

    Charis Eng

  49. London Health Sciences Centre, London, Canada

    Peter Ainsworth

  50. Mayo Clinic, Rochester, MN, USA

    Fergus Couch

  51. Medical University of Vienna, Vienna, Austria

    Christian Singer

  52. University of California, Los Angeles, CA, USA

    Beth Karlan

  53. University of Vermont, Burlington, VT, USA

    Wendy McKinnon & Marie Wood

Authors
  1. D. Gareth Evans
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  2. Kelly-Anne Phillips
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  3. Roger L. Milne
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  4. Robert Fruscio
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  5. Cezary Cybulski
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  6. Jacek Gronwald
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  7. Jan Lubinski
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  8. Tomasz Huzarski
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  9. Zerin Hyder
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  10. Claire Forde
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  11. Kelly Metcalfe
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  12. Leigha Senter
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  13. Jeffrey Weitzel
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  14. Nadine Tung
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  15. Dana Zakalik
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  16. Maria Ekholm
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  17. Ping Sun
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  18. Steven A. Narod
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Consortia

kConFab Investigators, Polish Hereditary Breast Cancer Consortium, Hereditary Breast Cancer Clinical Study Group

  • Other members of the Polish Hereditary Breast Cancer Consortium

    • Maria Błasińska-Morawiec
    • , Maria Chosia
    • , Kazimierz Drosik
    • , Sylwia Gozdecka-Grodecka
    • , Stanisław Goźdź
    • , Ewa Grzybowska
    • , Arkadiusz Jeziorski
    • , Aldona Karczewska
    • , Radzisław Kordek
    • , Agnieszka Synowiec
    • , Beata Kozak-Klonowska
    • , Katarzyna Lamperska
    • , Dariusz Lange
    • , Andrzej Mackiewicz
    • , Jerzy Władysław Mituś
    • , Stanislas Niepsuj
    • , Oleg Oszurek
    • , Karol Gugała
    • , Zbigniew Morawiec
    • , Tomasz Mierzwa
    • , Michał Posmyk
    • , Janusz Ryś
    • , Cezary Szczylik
    • , Michał Uciński
    • , Krzysztof Urbański
    • , Bernard Waśko
    •  & Piotr Wandzel

  • Other members of the kConFab Follow-Up Study Team

    • Michael Friedlander
    • , Sue Anne McLachlan
    • , Stephanie Nesci
    • , Sandra Picken
    • , Sarah O’Connor
    •  & Lucy Stanhope

  • Other members of Hereditary Breast Cancer Clinical Study Group

    • Andrea Eisen
    • , Kevin Sweet
    • , Raymond Kim
    • , William Foulkes
    • , Pal Moller
    • , Susan Neuhausen
    • , Carey Cullinane
    • , Charis Eng
    • , Peter Ainsworth
    • , Fergus Couch
    • , Christian Singer
    • , Beth Karlan
    • , Wendy McKinnon
    •  & Marie Wood

Contributions

Conception, design and study supervision: S.A.N. Acquisition of data: J.G., J.L., T.H., Z.H., C.F., K.M., L.S., D.Z. and M.E. Analysis of clinical data: R.F., J.L., C.C., D.Z., J.W. and N.T. Statistical analysis and critical review: P.S., R.L.M. and K.M. Interpretation of the results and writing of the original draft: D.G.E., S.A.N. and K.A.P. All authors revised the paper and approved the final version.

Corresponding author

Correspondence to Steven A. Narod.

Ethics declarations

Ethics approval and consent to participate

The study was approved by the following institutional ethics review boards: Women’s College Hospital Ethics Board, Research Ethics Committee of the Pomeranian Medical University, Central Manchester Research Ethics Committee (10/H1008/24 and 11/H1003/3), Peter MacCallum Cancer Centre Human Research Ethics Committee (97/27) and the Ethical Committee Brianza. All study subjects provided written informed consent. The study was performed in accordance with the Declaration of Helsinki.

Consent to publish

Individual person’s data not included.

Data availability

All data relevant to the study are included in the paper.

Competing interests

Steven A. Narod is a board member of BJC. All other authors declare no conflict of interest.

Funding information

This work was supported by grants to kConFab and the kConFab Follow-Up Study from Cancer Australia (809195, 1100868), the Australian National Breast Cancer Foundation (IF 17), the National Health and Medical Research Council (454508, 288704 and 145684), the National Institute of Health USA (1RO1CA159868), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia and the Cancer Foundation of Western Australia. K.A.P. is an Australian National Breast Cancer Foundation Fellow (PRAC17-004). The work is supported by the Peter Gilgan Center for Research on Women’s Cancers and the Canadian Institute of Health Research (FDN 154275). D.G.E. is supported by the NIHR Manchester Biomedical Research Centre (IS-BRC-1215-20007).

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Note This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Members of the Polish Breast Cancer Consortium, kConFab Follow-Up Study Team and Hereditary Breast Cancer Clinical Study Group are listed above Acknowledgements.

The original online version of this article was revised: The original version of this article unfortunately contained a mistake in an author affiliation. The correct affiliations of author Tomasz Huzarski are: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland and University of Zielona Góra, Zielona Góra, Poland.

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Evans, D.G., Phillips, KA., Milne, R.L. et al. Survival from breast cancer in women with a BRCA2 mutation by treatment. Br J Cancer 124, 1524–1532 (2021). https://doi.org/10.1038/s41416-020-01164-1

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