Skip to main content

Thank you for visiting 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:


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



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.


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.


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%.


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

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.


  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;

  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


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.


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




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).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


Quick links