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

Kelly Metcalfe; Tomasz Huzarski; Jacek Gronwald; Joanne Kotsopoulos; Raymond Kim; Pal Moller; Tuya Pal; Amber Aeilts; Andrea Eisen; Beth Karlan; Louise Bordeleau; Nadine Tung; Olufunmilayo Olopade; Dana Zakalik; Christian F. Singer; William Foulkes; Fergus Couch; Susan L. Neuhausen; Charis Eng; Ping Sun; Jan Lubinski; Steven A. Narod; 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

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, Tomasz Huzarski, Jacek Gronwald, Joanne Kotsopoulos, Raymond Kim, Pal Moller, Tuya Pal, Amber Aeilts, Andrea Eisen, Beth Karlan, Louise Bordeleau, Nadine Tung, Olufunmilayo Olopade, Dana Zakalik, Christian F. Singer, William Foulkes, Fergus Couch, Susan L. Neuhausen, Charis Eng, Ping SunJan Lubinski, Steven A. Narod^*, 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

^*Corresponding author for this work

Obstetrics and Gynecology

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

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.

Original language	English (US)
Pages (from-to)	269-274
Number of pages	6
Journal	British Journal of Cancer
Volume	130
Issue number	2
DOIs	https://doi.org/10.1038/s41416-023-02503-8
State	Published - Feb 10 2024

Funding

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.

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41416-023-02503-8

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Metcalfe, K., Huzarski, T., Gronwald, J., Kotsopoulos, J., Kim, R., Moller, P., Pal, T., Aeilts, A., Eisen, A., Karlan, B., Bordeleau, L., Tung, N., Olopade, O., Zakalik, D., Singer, C. F., Foulkes, W., Couch, F., Neuhausen, S. L., Eng, C., ... Cohen, S. (2024). Risk-reducing mastectomy and breast cancer mortality in women with a BRCA1 or BRCA2 pathogenic variant: an international analysis. British Journal of Cancer, 130(2), 269-274. https://doi.org/10.1038/s41416-023-02503-8

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

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.",

author = "Kelly Metcalfe and Tomasz Huzarski and Jacek Gronwald and Joanne Kotsopoulos and Raymond Kim and Pal Moller and Tuya Pal and Amber Aeilts and Andrea Eisen and Beth Karlan and Louise Bordeleau and Nadine Tung and Olufunmilayo Olopade and Dana Zakalik and Singer, {Christian F.} and William Foulkes and Fergus Couch and Neuhausen, {Susan L.} and Charis Eng and Ping Sun and Jan Lubinski and Narod, {Steven A.} and Lea Velsher and Aletta Poll and Ellen Warner and Jeanna McCuaig and Susan Armel and Howard Saal and Linda Steele and Edmond Lemire and Kim Serfas and Leigha Senter and Kevin Sweet and Seema Panchal and Cullinane, {Carey A.} and Blum, {Joanne L.} and Daniel Rayson and {Ram{\'o}n y Cajal}, Teresa and Jeffrey Dungan and Robert Fruscio and Stefania Zovato and Stephanie Cohen",

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Metcalfe, K, Huzarski, T, Gronwald, J, Kotsopoulos, J, Kim, R, Moller, P, Pal, T, Aeilts, A, Eisen, A, Karlan, B, Bordeleau, L, Tung, N, Olopade, O, Zakalik, D, Singer, CF, Foulkes, W, Couch, F, Neuhausen, SL, Eng, C, Sun, P, Lubinski, J, Narod, SA, Velsher, L, Poll, A, Warner, E, McCuaig, J, Armel, S, Saal, H, Steele, L, Lemire, E, Serfas, K, Senter, L, Sweet, K, Panchal, S, Cullinane, CA, Blum, JL, Rayson, D, Ramón y Cajal, T, Dungan, J, Fruscio, R, Zovato, S & Cohen, S 2024, 'Risk-reducing mastectomy and breast cancer mortality in women with a BRCA1 or BRCA2 pathogenic variant: an international analysis', British Journal of Cancer, vol. 130, no. 2, pp. 269-274. https://doi.org/10.1038/s41416-023-02503-8

TY - JOUR

T1 - Risk-reducing mastectomy and breast cancer mortality in women with a BRCA1 or BRCA2 pathogenic variant

T2 - an international analysis

AU - Metcalfe, Kelly

AU - Huzarski, Tomasz

AU - Gronwald, Jacek

AU - Kotsopoulos, Joanne

AU - Kim, Raymond

AU - Moller, Pal

AU - Pal, Tuya

AU - Aeilts, Amber

AU - Eisen, Andrea

AU - Karlan, Beth

AU - Bordeleau, Louise

AU - Tung, Nadine

AU - Olopade, Olufunmilayo

AU - Zakalik, Dana

AU - Singer, Christian F.

AU - Foulkes, William

AU - Couch, Fergus

AU - Neuhausen, Susan L.

AU - Eng, Charis

AU - Sun, Ping

AU - Lubinski, Jan

AU - Narod, Steven A.

AU - Velsher, Lea

AU - Poll, Aletta

AU - Warner, Ellen

AU - McCuaig, Jeanna

AU - Armel, Susan

AU - Saal, Howard

AU - Steele, Linda

AU - Lemire, Edmond

AU - Serfas, Kim

AU - Senter, Leigha

AU - Sweet, Kevin

AU - Panchal, Seema

AU - Cullinane, Carey A.

AU - Blum, Joanne L.

AU - Rayson, Daniel

AU - Ramón y Cajal, Teresa

AU - Dungan, Jeffrey

AU - Fruscio, Robert

AU - Zovato, Stefania

AU - Cohen, Stephanie

PY - 2024/2/10

Y1 - 2024/2/10

N2 - 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.

AB - 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.

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U2 - 10.1038/s41416-023-02503-8

DO - 10.1038/s41416-023-02503-8

M3 - Article

C2 - 38030749

AN - SCOPUS:85177744303

SN - 0007-0920

VL - 130

SP - 269

EP - 274

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 2

ER -

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

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UN SDGs

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