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Tamoxifen and the risk of breast cancer in women with a BRCA1 or BRCA2 mutation

  • Epidemiology
  • Published:
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Abstract

Purpose

Chemoprevention with a selective estrogen receptor modulator (tamoxifen or raloxifene) is a non-surgical option offered to high-risk women to reduce the risk of breast cancer. The evidence for tamoxifen benefit is based on trials conducted among predominantly postmenopausal women from the general population and on studies of contralateral breast cancer in women with a pathogenic variant (mutation hereafter) in BRCA1 or BRCA2. Tamoxifen has not been assessed as a primary prevention agent in women with an inherited BRCA mutation.

Methods

We conducted a prospective analysis of tamoxifen chemoprevention and the risk of breast cancer in women with a BRCA1 or BRCA2 mutation. Data on tamoxifen (and raloxifene) use was collected by questionnaire and updated biennially. Information on incident cancers was collected by self-report and was confirmed by medical record review. In a matched analysis, we estimated the hazard ratio (HR) and 95% confidence intervals (CI) for developing a first primary breast cancer associated with tamoxifen or raloxifene use, using Cox proportional hazards analysis.

Results

There were 4578 unaffected women in the cohort, of whom 137 reported tamoxifen use (3%), 83 reported raloxifene use (2%) and 12 used both drugs (0.3%). Women who used tamoxifen or raloxifene were matched 1:3 with women who used neither drug on year of birth, country of residence, year of study entry and gene (BRCA1 or BRCA2). We generated 202 matched pairs. After a mean follow-up of 6.8 years, there were 22 incident breast cancers diagnosed among tamoxifen/raloxifene users (10.9% of users) and 71 cases diagnosed among non-users (14.3% of non-users; HR = 0.64; 95% CI 0.40–1.03; P = 0.07).

Conclusion

Chemoprevention may be an effective risk-reduction option for BRCA mutation carriers, but further studies with longer follow-up are necessary.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Code availability

Available from the corresponding author upon reasonable request.

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Acknowledgements

We are grateful for the contributions of the women who participated in this study, without whom this research would not be possible. 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, Li Quan, Martina Delle Marchette, Serena Negri, Cristina Dell'Oro and Alessandra Inzoli.

Other members of the Hereditary Breast Cancer Clinical Study Group: Georgia Wiesner, Aletta Poll, Raymond Kim, Jeanna McCuaig, Dana Zakalik, Fergus Couch, Linda Steele, Howard Saal, Edmond Lemire, Kim Serfas, Kevin Sweet, Seema Panchal, Christine Elser, Robert E. Reilly, Joanne L. Blum, Cezary Cybulski, Daniel Rayson, Teresa Ramón y Cajal, Jeffrey Dungan, Stefania Zovato, Antonella Rastelli, Pal Moller, and Stephanie Cohen.

Funding

Steven A. Narod is the recipient of a Canada Research Chair (Tier I). Joanne Kotsopoulos is the recipient of a Canada Research Chair (Tier II). This work was supported by the Canadian Institutes of Health Research (FDN 154275), Canadian Cancer Society Research Institute grant (703058) and the Peter Gilgan Centre for Women’s Cancers at Women’s College Hospital, in partnership with the Canadian Cancer Society.

Author information

Authors and Affiliations

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

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

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

    Joanne Kotsopoulos & Steven A. Narod

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

    Jacek Gronwald, Tomasz Huzarski & Jan Lubinski

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

    Amber Aeilts

  5. Bhalwani Familial Cancer Clinic, Princess Margaret Cancer Centre, Toronto, Canada

    Susan Randall Armel

  6. Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada

    Susan Randall Armel

  7. David Geffen School of Medicine, UCLA, Los Angeles, CA, USA

    Beth Karlan

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

    Christian F. Singer

  9. Toronto-Sunnybrook Regional Cancer Center, Toronto, ON, Canada

    Andrea Eisen

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

    Nadine Tung

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

    Olufunmilayo Olopade

  12. Department of Oncology, Juravinski Cancer Centre and McMaster University, Hamilton, ON, Canada

    Louise Bordeleau

  13. Genomic Medicine Institute and Center for Personalized Genetic Healthcare, Cleveland Clinic, Cleveland, USA

    Charis Eng

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

    William D. Foulkes

  15. Division of Biomarkers of Early Detection and Prevention, City of Hope, Duarte, USA

    Susan L. Neuhausen

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

    Carey A. Cullinane

  17. Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA

    Tuya Pal

  18. Clinic of Obstetrics and Gynecology, Department of Medicine and Surgery, University of Milan Bicocca, Monza, Italy

    Robert Fruscio

  19. Bloomberg School of Nursing, University of Toronto, Toronto, ON, Canada

    Kelly Metcalfe

  20. Women’s College Research Institute, Women’s College Hospital, 76 Grenville St., 6Th Floor, Toronto, ON, M5S 1B2, Canada

    Steven A. Narod

Authors
  1. Joanne Kotsopoulos
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  2. Jacek Gronwald
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  3. Tomasz Huzarski
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  4. Amber Aeilts
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  5. Susan Randall Armel
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  6. Beth Karlan
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  7. Christian F. Singer
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  8. Andrea Eisen
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  9. Nadine Tung
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  12. Charis Eng
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  14. Susan L. Neuhausen
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  15. Carey A. Cullinane
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  16. Tuya Pal
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  18. Jan Lubinski
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  19. Kelly Metcalfe
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Consortia

and the Hereditary Breast Cancer Clinical Study Group

  • Georgia Wiesner
  • , Aletta Poll
  • , Raymond Kim
  • , Jeanna McCuaig
  • , Dana Zakalik
  • , Fergus Couch
  • , Linda Steele
  • , Howard Saal
  • , Edmond Lemire
  • , Kim Serfas
  • , Kevin Sweet
  • , Seema Panchal
  • , Christine Elser
  • , Robert E Reilly
  • , Joanne L Blum
  • , Cezary Cybulski
  • , Daniel Rayson
  • , Teresa y Cajal Ramón
  • , Jeffrey Dungan
  • , Stefania Zovato
  • , Antonella Rastelli
  • , Pal Moller
  •  & Stephanie Cohen

Contributions

JK and SAN: conceptualization, funding acquisition, investigation, methodology, project administration, supervision, writing. All authors contributed to data curation, project administration, manuscript review and editing. All data analyses were performed by PS. The first draft of the manuscript was written by JK and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Steven A. Narod.

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Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Women’s College Hospital Ethics Board. The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Consent for publication

Not applicable.

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The members of the Hereditary Breast Cancer Clinical Study Group are listed in acknowledgements section.

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Kotsopoulos, J., Gronwald, J., Huzarski, T. et al. Tamoxifen and the risk of breast cancer in women with a BRCA1 or BRCA2 mutation. Breast Cancer Res Treat 201, 257–264 (2023). https://doi.org/10.1007/s10549-023-06991-3

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