. 2025 Jul;133(1):104-110.

doi: 10.1038/s41416-025-03029-x. Epub 2025 May 2.

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

Joanne Kotsopoulos^{1

2}, Christopher A Maxwell³, Jan Lubinski⁴, Tomasz Huzarski⁴, Raymond H Kim⁵, Nadine Tung⁶, Andrea Eisen⁷, William Foulkes⁸, Amber Aeilts⁹, Susan L Neuhausen¹⁰, Louise Bordeleau¹¹, Rama Khokha¹², Tuya Pal¹³, Beth Karlan¹⁴, Robert Fruscio¹⁵, Fergus Couch¹⁶, Ping Sun¹, Jacek Gronwald⁴, Steven A Narod^{17

18}; Hereditary Breast Cancer Clinical Study Group

Collaborators, Affiliations

Collaborators

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

Affiliations

¹ Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada.
² Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
³ Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
⁴ International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
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.
⁶ Beth Israel Deaconess Medical Center, Boston, MA, USA.
⁷ Toronto-Sunnybrook Regional Cancer Center, Toronto, ON, Canada.
⁸ McGill Program in Cancer Genetics, Department of Oncology, McGill University, Montreal, QC, Canada.
⁹ Division of Human Genetics, The Ohio State University Medical Center, Comprehensive Cancer Center, Columbus, OH, USA.
¹⁰ Division of Biomarkers of Early Detection and Prevention, Department of Population Sciences, City of Hope, Duarte, CA, USA.
¹¹ Department of Oncology, McMaster University, Hamilton, ON, Canada.
¹² Department of Medical Biophysics, University of Toronto, Princess Margaret Cancer Centre, Toronto, ON, Canada.
¹³ Department of Medicine, Vanderbilt University, Nashville, TN, USA.
¹⁴ Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
¹⁵ Clinic of Obstetrics and Gynecology, IRCCS Fondazione San Gerardo dei Tintori, Monza, Italy.
¹⁶ Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
¹⁷ Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada. steven.narod@wchospital.ca.
¹⁸ Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. steven.narod@wchospital.ca.

PMID: 40316726
PMCID: PMC12238466 (available on 2026-05-02)
DOI: 10.1038/s41416-025-03029-x

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

Joanne Kotsopoulos et al. Br J Cancer. 2025 Jul.

. 2025 Jul;133(1):104-110.

doi: 10.1038/s41416-025-03029-x. Epub 2025 May 2.

Authors

Collaborators

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

Affiliations

¹ Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada.
² Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
³ Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
⁴ International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
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.
⁶ Beth Israel Deaconess Medical Center, Boston, MA, USA.
⁷ Toronto-Sunnybrook Regional Cancer Center, Toronto, ON, Canada.
⁸ McGill Program in Cancer Genetics, Department of Oncology, McGill University, Montreal, QC, Canada.
⁹ Division of Human Genetics, The Ohio State University Medical Center, Comprehensive Cancer Center, Columbus, OH, USA.
¹⁰ Division of Biomarkers of Early Detection and Prevention, Department of Population Sciences, City of Hope, Duarte, CA, USA.
¹¹ Department of Oncology, McMaster University, Hamilton, ON, Canada.
¹² Department of Medical Biophysics, University of Toronto, Princess Margaret Cancer Centre, Toronto, ON, Canada.
¹³ Department of Medicine, Vanderbilt University, Nashville, TN, USA.
¹⁴ Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
¹⁵ Clinic of Obstetrics and Gynecology, IRCCS Fondazione San Gerardo dei Tintori, Monza, Italy.
¹⁶ Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
¹⁷ Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada. steven.narod@wchospital.ca.
¹⁸ Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. steven.narod@wchospital.ca.

PMID: 40316726
PMCID: PMC12238466 (available on 2026-05-02)
DOI: 10.1038/s41416-025-03029-x

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.

PubMed Disclaimer

Conflict of interest statement

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.

References

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. - PubMed
1. Mavaddat N, Barrowdale D, Andrulis IL, Domchek SM, Eccles D, Nevanlinna H, et al. Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Cancer Epidemiol Biomark Prev. 2012;21:134–47. - PMC - PubMed
1. Hartmann LC, Schaid DJ, Woods JE, Crotty TP, Myers JL, Arnold PG, et al. Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. N. Engl J Med. 1999;340:77–84. - PubMed
1. Nolan E, Vaillant F, Branstetter D, Pal B, Giner G, Whitehead L, et al. RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers. Nat Med. 2016;22:933–9. - PubMed
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Parity, breastfeeding, and the risk of early-onset breast cancer in women with a BRCA1 pathogenic variant

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

References

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous