. 2024 Feb;130(2):269-274.

doi: 10.1038/s41416-023-02503-8. Epub 2023 Nov 29.

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

Kelly Metcalfe^{1

2}, Tomasz Huzarski³, Jacek Gronwald³, Joanne Kotsopoulos^{1

4}, Raymond Kim⁵, Pal Moller⁶, Tuya Pal⁷, Amber Aeilts⁸, Andrea Eisen⁹, Beth Karlan¹⁰, Louise Bordeleau¹¹, Nadine Tung¹², Olufunmilayo Olopade¹³, Dana Zakalik¹⁴, Christian F Singer¹⁵, William Foulkes¹⁶, Fergus Couch¹⁷, Susan L Neuhausen¹⁸, Charis Eng¹⁹, Ping Sun¹, Jan Lubinski³, Steven A Narod^{20

21}; Hereditary Breast Cancer Clinical Study Group

Collaborators, Affiliations

Collaborators

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

Affiliations

¹ Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada.
² Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, ON, Canada.
³ International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
⁴ Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
⁵ Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
⁶ The Norwegian Radium Hospital, Department for Medical Genetics, Oslo University Hospital, Oslo, Norway.
⁷ Department of Medicine, Vanderbilt University, Nashville, TN, USA.
⁸ Division of Human Genetics, The Ohio State University Medical Center, Comprehensive Cancer Center, Columbus, OH, USA.
⁹ Department of Medical Oncology, Sunnybrook Odette Cancer Center and University of Toronto, Toronto, ON, Canada.
¹⁰ Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
¹¹ Department of Oncology, Juravinski Cancer Centre, Hamilton, ON, Canada.
¹² Beth Israel Deaconess Medical Center, Cancer Risk and Prevention Program, Boston, MA, USA.
¹³ Department of Medicine and Human Genetics, University of Chicago, Chicago, IL, USA.
¹⁴ Cancer Genetics Program, Beaumont Hospital, Royal Oak, MI, USA.
¹⁵ Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
¹⁶ McGill Program in Cancer Genetics, Department of Oncology, McGill University, Montreal, QC, Canada.
¹⁷ Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
¹⁸ Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.
¹⁹ Genomic Medicine Institute, Center for Personalized Genetic Healthcare, Cleveland Clinic, Cleveland, OH, USA.
²⁰ Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada. steven.narod@wchospital.ca.
²¹ Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. steven.narod@wchospital.ca.

PMID: 38030749
PMCID: PMC10803363
DOI: 10.1038/s41416-023-02503-8

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

Kelly Metcalfe et al. Br J Cancer. 2024 Feb.

. 2024 Feb;130(2):269-274.

doi: 10.1038/s41416-023-02503-8. Epub 2023 Nov 29.

Authors

Collaborators

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

Affiliations

¹ Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada.
² Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, ON, Canada.
³ International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
⁴ Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
⁵ Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
⁶ The Norwegian Radium Hospital, Department for Medical Genetics, Oslo University Hospital, Oslo, Norway.
⁷ Department of Medicine, Vanderbilt University, Nashville, TN, USA.
⁸ Division of Human Genetics, The Ohio State University Medical Center, Comprehensive Cancer Center, Columbus, OH, USA.
⁹ Department of Medical Oncology, Sunnybrook Odette Cancer Center and University of Toronto, Toronto, ON, Canada.
¹⁰ Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
¹¹ Department of Oncology, Juravinski Cancer Centre, Hamilton, ON, Canada.
¹² Beth Israel Deaconess Medical Center, Cancer Risk and Prevention Program, Boston, MA, USA.
¹³ Department of Medicine and Human Genetics, University of Chicago, Chicago, IL, USA.
¹⁴ Cancer Genetics Program, Beaumont Hospital, Royal Oak, MI, USA.
¹⁵ Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
¹⁶ McGill Program in Cancer Genetics, Department of Oncology, McGill University, Montreal, QC, Canada.
¹⁷ Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
¹⁸ Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.
¹⁹ Genomic Medicine Institute, Center for Personalized Genetic Healthcare, Cleveland Clinic, Cleveland, OH, USA.
²⁰ Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada. steven.narod@wchospital.ca.
²¹ Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. steven.narod@wchospital.ca.

PMID: 38030749
PMCID: PMC10803363
DOI: 10.1038/s41416-023-02503-8

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.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

**Fig. 1. Breast Cancer Incidence.**
Cumulative incidence of breast cancer from index date for RRM versus Control.

See this image and copyright information in PMC

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. doi: 10.1086/375033. - DOI - PMC - PubMed
1. 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. doi: 10.1001/jama.2017.7112. - DOI - PubMed
1. 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. doi: 10.1056/NEJMoa031759. - DOI - PubMed
1. 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. doi: 10.1200/JCO.2001.19.15.3524. - DOI - PubMed
1. 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. doi: 10.1001/jama.292.11.1317. - DOI - PubMed

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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous