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Epidemiology

Parity, breastfeeding, and the risk of early-onset breast cancer in women with a BRCA1 pathogenic variant

British Journal of Cancer volume 133, pages 104–110 (2025)Cite this article

Subjects

Abstract

Background

It is not clear if breastfeeding and/or parity are associated with the risk of breast cancer among women with a germline pathogenic variant in BRCA1. We sought to evaluate the associations of these two factors with early-onset breast cancer in the BRCA1 pathogenic variant.

Methods

This case-control study included individuals with a BRCA1 pathogenic variant enroled in a longitudinal study using reproductive and disease histories ascertained at the time of enrolment. Cases had invasive breast cancer prior to age 45, and controls had no breast cancer prior to age 45. Logistic regression was used to evaluate the associations of parity and breastfeeding with cancer risk.

Results

Parity per se was not associated with breast cancer risk (OR = 1.09; 95%CI 0.95–1.25); however, among women who never breastfed, the OR for parous vs. nulliparous women was 1.45 (95%CI 1.20–1.75). After matching for parity, ever breastfeeding was associated with 25% lower odds of breast cancer (95%CI 0.61–0.91), and the odds ratio was 0.53 (95%CI 0.40–0.72) for those who breastfed for 20 or more months.

Discussion

Our findings suggest a potential role for breastfeeding in the prevention of young-onset breast cancer among individuals with a BRCA1 pathogenic variant and provide insight into possible prevention targets.

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Data availability

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

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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 Fatima, Rebecca Raj, Pooja Chaudhary, Pooja Patel, Suvetha Krishnapillai, Banafsheh Mesbahi, Angela Cheriyan, Anasua Kundu, Nurun Nahar, Abigail Sims, Alexandra Parco, Christine Zhu, Cindy Zhang, Elizabeth Hall, Lisa Asbroek, Izzar Linares, Shaelyn Laurie, Kamrun Urmi, Amina Mahmood, Mayra Gholizadeh, Nazia Awan, Neelam Dehal, Yasmin Tehrani, Jasdeep Brar, Marsela Supriadi, Jenani Anantharajah, Grace Li, Hannah Horvath, Laavanya Somasundaram, Anne Matip, Forough Armaghan, Mohamed Bekkouche, Yasaman Ghazi, Qadriy Naimi, Miao Jia, Li Quan, Angelo Wang, Baker Hawa, Bhakti Almoula, Bhumi Patel, Brynne Stewart, Charlotte Francis, Cynthia (Chen) Ji, Fabiah Mahmood, Fahmida Rahman, Jasdeep Brar, Jenani Anantharajah, Jie Zhaung, Leila Gayo, Liao Jia, Madeline Firmanto, Matthew Gertig, Mayra Robalino, Rachel Trister, Sheena Sajan, Sukhnit Kandola, Martina Delle Marchette, Serena Negri, Cristina Dell’Oro, Alessandra Inzoli, Rosa Alfonso, Consol Lopez and Francesco Cusco.

Funding

Joanne Kotsopoulos is a recipient of a Tier II Canada Research Chair. Steven A. Narod is the recipient of a Tier I Canada Research Chair. Charis Eng is the Sondra J. and Stephen R. Hardis Endowed Chair of Cancer Genomic Medicine at the Cleveland Clinic. This work was supported by a Canadian Cancer Society Research Institute grant (703058), a Terry Fox Program Project grant (TFP-185032), the Peter Gilgan Foundation, and a Contract 194751-2017 from Norwegian Cancer Society. Funding supported the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Author information

Authors and Affiliations

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

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

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

    Joanne Kotsopoulos & Steven A. Narod

  3. Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada

    Christopher A. Maxwell

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

    Jan Lubinski, Tomasz Huzarski, Jacek Gronwald & Cezary Cybulski

  5. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Sinai Health System, Hospital for Sick Children, Ontario Institute for Cancer Research, Department of Medicine, University of Toronto, Toronto, ON, Canada

    Raymond H. Kim

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

    Nadine Tung

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

    Andrea Eisen

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

    William Foulkes

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

    Amber Aeilts

  10. Division of Biomarkers of Early Detection and Prevention, Department of Population Sciences, City of Hope, Duarte, CA, USA

    Susan L. Neuhausen

  11. Department of Oncology, McMaster University, Hamilton, ON, Canada

    Louise Bordeleau

  12. Department of Medical Biophysics, University of Toronto, Princess Margaret Cancer Centre, Toronto, ON, Canada

    Rama Khokha

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

    Tuya Pal

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

    Beth Karlan

  15. Clinic of Obstetrics and Gynecology, IRCCS Fondazione San Gerardo dei Tintori, Monza, Italy

    Robert Fruscio

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

    Fergus Couch

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

    Georgia Wiesner

  18. Princess Margaret Hospital—Cancer Centre—Toronto, Toronto, ON, Canada

    Jeanna McCuaig

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

    Dana Zakalik

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

    Linda Steele

  21. Division of Human Genetics, Cincinnati Children’s Hospital, Cincinnati, OH, USA

    Howard Saal

  22. Division of Medical Genetics, Department of Pediatrics, University of Saskatchewan, Saskatoon, SK, Canada

    Edmond Lemire

  23. Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada

    Kim Serfas

  24. Division of Human Genetics, Ohio State University Wexner Medical Center, Columbus, OH, USA

    Kevin Sweet

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

    Seema Panchal

  26. Princess Margaret Cancer Centre, Mount Sinai Hospital, University of Toronto, Toronto, Canada

    Christine Elser

  27. St. Mary’s Hospital Center, Lewiston, NY, USA

    Robert E. Reilly

  28. The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Joanne L. Blum

  29. Queen Elizabeth II Health Science Centre, Halifax, NS, Canada

    Daniel Rayson

  30. Familial Cancer Clinic. Medical Oncology. Hospital Santa Creu i Sant Pau, Barcelona, Spain

    Teresa Ramón y. Cajal

  31. Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Jeffrey Dungan

  32. Familial Cancer Clinics, Istituto Oncologico Veneto, IRCCS, Padova, Italy

    Stefania Zovato

  33. Unità Tumori Ereditari, Istituto Oncologico Veneto, IRCCS Padova, Padova, Italy

    Antonella Rastelli

  34. Department of Tumour Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo, Norway

    Pal Moller

  35. Department of Dermatology, Tufts Medical Center, Boston, MA, USA

    Stephanie Cohen

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

    Christian F. Singer

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

    Charis Eng

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

    Olufunmilayo Olopade

Authors
  1. Joanne Kotsopoulos
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  2. Christopher A. Maxwell
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  3. Jan Lubinski
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  4. Tomasz Huzarski
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  5. Raymond H. Kim
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  6. Nadine Tung
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  7. Andrea Eisen
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  8. William Foulkes
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  9. Amber Aeilts
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  10. Susan L. Neuhausen
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  11. Louise Bordeleau
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  12. Rama Khokha
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  13. Tuya Pal
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  14. Beth Karlan
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  15. Robert Fruscio
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  16. Fergus Couch
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  17. Ping Sun
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  18. Jacek Gronwald
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  19. Steven A. Narod
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Consortia

on behalf of the Hereditary Breast Cancer Clinical Study Group

  • Georgia Wiesner
  • , Aletta Poll
  • , Jeanna McCuaig
  • , Dana Zakalik
  • , 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
  • , Stephanie Cohen
  • , Christian F. Singer
  • , Charis Eng
  •  & Olufunmilayo Olopade

Contributions

Study conception, study design, and methodology (SAN, JK, CM). Funding acquisition (SAN, JK). Data curation (SAN, JK, PS). Formal analysis (PS, SN, JK). Drafting of manuscript (SAN, JK, CS). Data contribution (JK, CAM, JL, TH, RHK, NT, AE, WF, AA, SLN, LB, RK, TP, BK, RF, FC, PS, JG, SAN). Review and editing of manuscript (JK, CAM, JL, TH, RHK, NT, AE, WF, AA, SLN, LB, RK, TP, BK, RF, FC, PS, JG, SAN).

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.

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Kotsopoulos, J., Maxwell, C.A., Lubinski, J. et al. Parity, breastfeeding, and the risk of early-onset breast cancer in women with a BRCA1 pathogenic variant. Br J Cancer 133, 104–110 (2025). https://doi.org/10.1038/s41416-025-03029-x

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