Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Epidemiology

Risk-reducing mastectomy and breast cancer mortality in women with a BRCA1 or BRCA2 pathogenic variant: an international analysis

British Journal of Cancer volume 130, pages 269–274 (2024)Cite this article

Subjects

Abstract

Background

Risk-reducing mastectomy (RRM) is offered to women with a BRCA1 or BRCA2 pathogenic variant, however, there are limited data on the impact on breast cancer mortality.

Methods

Participants were identified from a registry of women with BRCA1/2 pathogenic variants. We used a pseudo-randomised trial design and matched one woman with a RRM to one woman without a RRM on year of birth, gene, and country. We estimated the hazard ratio (HR) and 95% confidence intervals (CI) for dying of breast cancer in the follow-up period.

Results

There were 1654 women included; 827 assigned to the RRM arm and 827 assigned to the control arm. After a mean follow-up of 6.3 years, there were 20 incident breast cancers (including 15 occult cancers) and two breast cancer deaths in the RRM arm, and 100 incident breast cancers and 7 breast cancer deaths in the control arm (HR = 0.26; 95% CI 0.05–1.35; p = 0.11). The probability of dying of breast cancer within 15 years after RRM was 0.95%.

Conclusions

In women with a BRCA1 or BRCA2 pathogenic variant, RRM reduces the risk of breast cancer, and the probability of dying of breast cancer is low.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Breast Cancer Incidence.

Similar content being viewed by others

Data availability

All data are original, and consent was not obtained from participants to make data externally available.

References

  1. Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet. 2003;72:1117–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips KA, Mooij TM, Roos-Blom MJ, et al. Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers. JAMA. 2017;317:2402–16.

    Article  CAS  PubMed  Google Scholar 

  3. Kriege M, Brekelmans CT, Boetes C, Besnard PE, Zonderland HM, Obdeijn IM, et al. Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. N. Engl J Med. 2004;351:427–37.

    Article  CAS  PubMed  Google Scholar 

  4. Warner E, Plewes DB, Shumak RS, Catzavelos GC, Di Prospero LS, Yaffe MJ, et al. Comparison of breast magnetic resonance imaging, mammography, and ultrasound for surveillance of women at high risk for hereditary breast cancer. J Clin Oncol. 2001;19:3524–31.

    Article  CAS  PubMed  Google Scholar 

  5. Warner E, Plewes DB, Hill KA, Causer PA, Zubovits JT, Jong RA, et al. Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. JAMA. 2004;292:1317–25.

    Article  CAS  PubMed  Google Scholar 

  6. Kuhl CK, Schrading S, Leutner CC, Morakkabati-Spitz N, Wardelmann E, Fimmers R, et al. Mammography, breast ultrasound, and magnetic resonance imaging for surveillance of women at high familial risk for breast cancer. J Clin Oncol. 2005;23:8469–76.

    Article  PubMed  Google Scholar 

  7. Leach MO, Boggis CR, Dixon AK, Easton DF, Eeles RA, Evans DG, et al. Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS). Lancet. 2005;365:1769–78.

    Article  CAS  PubMed  Google Scholar 

  8. Heemskerk-Gerritsen BAM, Jager A, Koppert LB, Obdeijn AI, Collee M, Meijers-Heijboer HEJ, et al. Survival after bilateral risk-reducing mastectomy in healthy BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat. 2019;177:723–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hartmann LC, Sellers TA, Schaid DJ, Frank TS, Soderberg CL, Sitta DL, et al. Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers. J Natl Cancer Inst. 2001;93:1633–7.

    Article  CAS  PubMed  Google Scholar 

  10. Rebbeck TR, Friebel T, Lynch HT, Neuhausen SL, van ‘t Veer L, Garber JE, et al. Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol. 2004;22:1055–62.

    Article  PubMed  Google Scholar 

  11. Domchek SM, Friebel TM, Singer CF, Evans DG, Lynch HT, Isaacs C, et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA. 2010;304:967–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Genetic/Familal High-Risk Assessment: Breast, Ovarian, and Pancreatic; Version 2.2024; https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf.

  13. Metcalfe K, Eisen A, Senter L, Armel S, Bordeleau L, Meschino WS, et al. International trends in the uptake of cancer risk reduction strategies in women with a BRCA1 or BRCA2 mutation. Br J Cancer. 2019;121:15–21.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Giannakeas V, Sopik V, Narod S. A Validation of Methods for the Evaluation of Observational Studies of Screening Mammography: An Exploratory Analysis Based on Simulating Screening Cohorts. Clin Epidemiol. 2020;12:1161–9.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Krajewski AC, Boughey JC, Degnim AC, Jakub JW, Jacobson SR, Hoskin TL, et al. Expanded Indications and Improved Outcomes for Nipple-Sparing Mastectomy Over Time. Ann Surg Oncol. 2015;22:3317–23.

    Article  PubMed  Google Scholar 

  16. Jakub JW, Peled AW, Gray RJ, Greenup RA, Kiluk JV, Sacchini V, et al. Oncologic Safety of Prophylactic Nipple-Sparing Mastectomy in a Population With BRCA Mutations: A Multi-institutional Study. JAMA Surg. 2018;153:123–9.

    Article  PubMed  Google Scholar 

  17. Metcalfe K, Lynch HT, Foulkes WD, Tung N, Kim-Sing C, Olopade OI, et al. Effect of Oophorectomy on Survival After Breast Cancer in BRCA1 and BRCA2 Mutation Carriers. JAMA Oncol. 2015;1:306–13.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful for the contributions of the women who participated in this study, without whom this research would not be possible. We are thankful for the support of the Peter Gilgan Centre for Women’s Cancers at Women’s College Hospital in partnership with the Canadian Cancer Society. SAN is the recipient of a Tier I Canada Research Chair. This work was supported by a Canadian Institute of Health Research. We acknowledge the study staff, students, and volunteers who assisted with data collection and data entry: Ellen MacDougall, Shana Kim, Clotilde Ngwa, Aiman Syeda, Anasua Kundu, Nurun Nahar, Abigail Sims, Alexandra Parco, Christine Zhu, Cindy Zhang, Elizabeth Hall, Lisa Asbroek, Rebecca Raj, Izzar Linares, Shaelyn Laurie, Kamrun Urmi, Amina Mahmood, Mayra Gholizadeh, Nazia Awan, Neelam Dehal, Pooja Chaudhary, Pooja Patel, Yasmin Tehrani, Seetha Venkatewsaran, Seema Mehta, Jasdeep Brar, Marsela Supriadi, Jenani Anantharajah, Grace Li, Hannah Horvath, Laavanya Somasundaram, Anne Matip, Forough Armaghan, Mohamed Bekkouche, Yasaman Ghazi, Qadriy Naimi, Liao Jia, and Li Quan.

Funding

This study was funded through the Canadian Institutes of Health Research and the Peter Gilgan Centre for Women’s Cancers at Women’s College Hospital.

Author information

Authors and Affiliations

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

    Kelly Metcalfe, Joanne Kotsopoulos, Ping Sun, Steven A. Narod & Aletta Poll

  2. Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, ON, Canada

    Kelly Metcalfe

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

    Tomasz Huzarski, Jacek Gronwald & Jan Lubinski

  4. Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada

    Joanne Kotsopoulos & Steven A. Narod

  5. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada

    Raymond Kim & Jeanna McCuaig

  6. The Norwegian Radium Hospital, Department for Medical Genetics, Oslo University Hospital, Oslo, Norway

    Pal Moller

  7. Department of Medicine, Vanderbilt University, Nashville, TN, USA

    Tuya Pal

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

    Amber Aeilts, Leigha Senter & Kevin Sweet

  9. Department of Medical Oncology, Sunnybrook Odette Cancer Center and University of Toronto, Toronto, ON, Canada

    Andrea Eisen

  10. Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA

    Beth Karlan

  11. Department of Oncology, Juravinski Cancer Centre, Hamilton, ON, Canada

    Louise Bordeleau

  12. Beth Israel Deaconess Medical Center, Cancer Risk and Prevention Program, Boston, MA, USA

    Nadine Tung

  13. Department of Medicine and Human Genetics, University of Chicago, Chicago, IL, USA

    Olufunmilayo Olopade

  14. Cancer Genetics Program, Beaumont Hospital, Royal Oak, MI, USA

    Dana Zakalik

  15. Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria

    Christian F. Singer

  16. McGill Program in Cancer Genetics, Department of Oncology, McGill University, Montreal, QC, Canada

    William Foulkes

  17. Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    Fergus Couch

  18. Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA

    Susan L. Neuhausen & Linda Steele

  19. Genomic Medicine Institute, Center for Personalized Genetic Healthcare, Cleveland Clinic, Cleveland, OH, USA

    Charis Eng

  20. North York General Hospital, Toronto, ON, Canada

    Lea Velsher

  21. Division of Medical Oncology, Medical Oncology, Odette Cancer Centre of Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    Ellen Warner

  22. Bhalwani Familial Cancer Clinic, Princess Margaret Cancer Centre, Toronto, ON, M5G 2C1, Canada

    Susan Armel

  23. Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Howard Saal

  24. Division of Medical Genetics, University of Saskatchewan, Royal University Hospital, Saskatoon, SK, Canada

    Edmond Lemire

  25. Shared Health Program of Genetics and Metabolism, Health Sciences Centre, Winnipeg, MB, Canada

    Kim Serfas

  26. The Marvelle Koffler Breast Centre, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada

    Seema Panchal

  27. Todd Cancer Institute, Long Beach Memorial Hospital, Long Beach, CA, USA

    Carey A. Cullinane

  28. Department of Oncology, Texas Oncology-Baylor Charles A. Sammons Cancer Center, US Oncology Network, Dallas, TX, USA

    Joanne L. Blum

  29. Department of Medical Oncology, Dalhousie University, QEII-Bethune Building, 1276 South Park Street, Halifax, NS, B3H 2Y9, Canada

    Daniel Rayson

  30. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    Teresa Ramón y Cajal

  31. Prentice Women’s Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Jeffrey Dungan

  32. Clinic of Obstetrics and Gynecology, Department of Medicine and Surgery, University of Milan-Bicocca, Fondazione IRCCS San Gerardo, Monza, Italy

    Robert Fruscio

  33. Familial Cancer Unit, Veneto Institute of Oncology IOV IRCSS, 35128, Padova, Italy

    Stefania Zovato

  34. Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Stephanie Cohen

Authors
  1. Kelly Metcalfe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tomasz Huzarski
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jacek Gronwald
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joanne Kotsopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Raymond Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pal Moller
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tuya Pal
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Amber Aeilts
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Andrea Eisen
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Beth Karlan
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Louise Bordeleau
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Nadine Tung
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Olufunmilayo Olopade
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Dana Zakalik
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Christian F. Singer
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. William Foulkes
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Fergus Couch
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Susan L. Neuhausen
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Charis Eng
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Ping Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Jan Lubinski
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Steven A. Narod
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

the Hereditary Breast Cancer Clinical Study Group

  • Lea Velsher
  • , Aletta Poll
  • , Ellen Warner
  • , Jeanna McCuaig
  • , Susan Armel
  • , Howard Saal
  • , Linda Steele
  • , Edmond Lemire
  • , Kim Serfas
  • , Leigha Senter
  • , Kevin Sweet
  • , Seema Panchal
  • , Carey A. Cullinane
  • , Joanne L. Blum
  • , Daniel Rayson
  • , Teresa Ramón y Cajal
  • , Jeffrey Dungan
  • , Robert Fruscio
  • , Stefania Zovato
  •  & Stephanie Cohen

Contributions

Concept and design—KM, SN. Data accrual—TH, JG, JK, RK, PM, TP, AA, AE, BK, LB, NT, OO, DZ, CFS, WF, FC, SLN, CE, JL. Drafting of manuscript—KM, SN. Statistical analysis—PS, SN. Final approval of manuscript—all authors.

Corresponding author

Correspondence to Steven A. Narod.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics Approval and Consent to Participate

This study was approved by the Research Ethics Board at Women’s College Hospital, and consent was obtained from participants. The study was performed in accordance with the Declaration of Helsinki.

Additional information

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Metcalfe, K., Huzarski, T., Gronwald, J. et al. Risk-reducing mastectomy and breast cancer mortality in women with a BRCA1 or BRCA2 pathogenic variant: an international analysis. Br J Cancer 130, 269–274 (2024). https://doi.org/10.1038/s41416-023-02503-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41416-023-02503-8

Search

Advanced search

Quick links