American Society of Clinical Oncology (ASCO)

Journal of Clinical Oncology

, volume 43 , issue 4 , pages 422-431

Hormonal Contraception and Breast Cancer Risk for Carriers of Germline Mutations in BRCA1 and BRCA2

Courtney MacDonald ^{1, 2, 3}

Joanne Kotsopoulos ^{4, 5}

Susan M. Domchek ^{6, 7}

Mary Beth Terry ^{8, 9}

James A Chamberlain ¹⁰

Julie Bassett ¹⁰

Amber M Aeilts ¹¹

I Andrulis ^{12, 13}

Saundra S Buys ¹⁴

Wanyuan Cui ^{1, 2}

Mary B. Daly ¹⁵

Andrea F Eisen ^{16, 17}

William D. Foulkes ¹⁸

Michael Friedlander ^{19, 20}

Jacek Gronwald ²¹

J. HOPPER ³

E John ^{22, 23, 24}

Beth Y. Karlan ^{25, 26}

Raymond H. Kim ^{27, 28}

Allison W Kurian ^{22, 23, 24}

J. Lubinski ²¹

Kelly Metcalfe ^{4, 29}

Katherine L. Nathanson ^{6, 7, 30}

Christian F. Singer ³¹

Melissa C Southey ^{10, 32, 33}

Heather Symecko ⁶

Nadine M. Tung ³⁴

S. A. Narod ^{4, 5}

R W Milne ^{3, 10, 33}

Hide authors affiliations Show authors affiliations: 34 affiliations

Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia |

Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia |

Centre for Epidemiology and Biostatistics, School of Population and Global health, The University of Melbourne, Melbourne, VIC, Australia |

⁴

Women's College Research Institute, Women's College Hospital, University of Toronto, Toronto, ON, Canada

University of Toronto

Women's College Hospital

⁵

Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada |

⁶

Basser Center for BRCA, University of Pennsylvania, Philadelphia, PA |

⁷

Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA |

⁸

Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY |

⁹

Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY |

¹⁰

Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia |

¹¹

Division of Human Genetics, Department of Internal Medicine, The Ohio State University, Columbus, Ohio |

¹²

Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada |

¹³

Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada |

¹⁴

Department of Internal Medicine and Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah |

¹⁵

Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA |

¹⁶

Odette Cancer Centre, Sunnybrook Health Sciences, Toronto, ON, Canada |

¹⁷

Department of Medicine, University of Toronto, Toronto, ON, Canada |

¹⁸

Department of Human Genetics, McGill University, Montreal, QC, Canada |

¹⁹

Department of Medical Oncology, Prince of Wales and Royal Hospital for Women, Sydney, NSW, Australia |

²⁰

School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia |

²¹

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

²²

Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California |

²³

Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, California |

²⁴

Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California |

²⁵

Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA |

²⁶

Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA |

²⁷

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network and Sinai Health, Toronto, ON, Canada |

²⁸

Ontario Institute for Cancer Research, Toronto, ON, Canada |

²⁹

Bloomberg School of Nursing, University of Toronto, Toronto, ON, Canada |

³⁰

Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA |

³¹

Department of Obstetrics and Gynecology and Center for Breast Health, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria |

³²

Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Melbourne, VIC, Australia |

³³

Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia

Monash University

Monash Health

³⁴

BETH ISRAEL DEACONESS MEDICAL CENTER, BOSTON, MA |

Publication type: Journal Article

Publication date: 2025-02-01

American Society of Clinical Oncology (ASCO)

Journal of Clinical Oncology

scimago Q1

wos Q1

SJR: 11.205

CiteScore: 38.9

Impact factor: 41.9

ISSN: 0732183X, 15277755

DOI: 10.1200/jco.24.00176

Copy DOI

PubMed ID: 39356978

Abstract

PURPOSE

It is uncertain whether, and to what extent, hormonal contraceptives increase breast cancer (BC) risk for germline BRCA1 or BRCA2 mutation carriers.

METHODS

Using pooled observational data from four prospective cohort studies, associations between hormonal contraceptive use and BC risk for unaffected female BRCA1 and BRCA2 mutation carriers were assessed using Cox regression.

RESULTS

Of 3,882 BRCA1 and 1,509 BRCA2 mutation carriers, 53% and 71%, respectively, had ever used hormonal contraceptives for at least 1 year (median cumulative duration of use, 4.8 and 5.7 years, respectively). Overall, 488 BRCA1 and 191 BRCA2 mutation carriers developed BC during median follow-up of 5.9 and 5.6 years, respectively. Although for BRCA1 mutation carriers, neither current nor past use of hormonal contraceptives for at least 1 year was statistically significantly associated with BC risk (hazard ratio [HR], 1.40 [95% CI, 0.94 to 2.08], P = .10 for current use; 1.16 [0.80 to 1.69], P = .4, 1.40 [0.99 to 1.97], P = .05, and 1.27 [0.98 to 1.63], P = .07 for past use 1-5, 6-10, and >10 years before, respectively), ever use was associated with increased risk (HR, 1.29 [95% CI, 1.04 to 1.60], P = .02). Furthermore, BC risk increased with longer cumulative duration of use, with an estimated proportional increase in risk of 3% (1%-5%, P = .002) for each additional year of use. For BRCA2 mutation carriers, there was no evidence that current or ever use was associated with increased BC risk (HR, 0.70 [95% CI, 0.33 to 1.47], P = .3 and 1.07 [0.73 to 1.57], P = .7, respectively).

CONCLUSION

Hormonal contraceptives were associated with increased BC risk for BRCA1 mutation carriers, especially if used for longer durations. Decisions about their use in women with BRCA1 mutations should carefully weigh the risks and benefits for each individual.

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MacDonald C. et al. Hormonal Contraception and Breast Cancer Risk for Carriers of Germline Mutations in BRCA1 and BRCA2 // Journal of Clinical Oncology. 2025. Vol. 43. No. 4. pp. 422-431.

GOST all authors (up to 50) Copy

MacDonald C. et al. Hormonal Contraception and Breast Cancer Risk for Carriers of Germline Mutations in BRCA1 and BRCA2 // Journal of Clinical Oncology. 2025. Vol. 43. No. 4. pp. 422-431.

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BibTex (up to 50 authors) Copy

@article{2025_MacDonald,

author = {Courtney MacDonald and Joanne Kotsopoulos and Susan M. Domchek and Mary Beth Terry and James A Chamberlain and Julie Bassett and Amber M Aeilts and I Andrulis and Saundra S Buys and Wanyuan Cui and Mary B. Daly and Andrea F Eisen and William D. Foulkes and Michael Friedlander and Jacek Gronwald and J. HOPPER and E John and Beth Y. Karlan and Raymond H. Kim and Allison W Kurian and J. Lubinski and Kelly Metcalfe and Katherine L. Nathanson and Christian F. Singer and Melissa C Southey and Heather Symecko and Nadine M. Tung and S. A. Narod and R W Milne and others},

title = {Hormonal Contraception and Breast Cancer Risk for Carriers of Germline Mutations in BRCA1 and BRCA2},

journal = {Journal of Clinical Oncology},

year = {2025},

volume = {43},

publisher = {American Society of Clinical Oncology (ASCO)},

month = {feb},

url = {https://ascopubs.org/doi/10.1200/JCO.24.00176},

number = {4},

pages = {422--431},

doi = {10.1200/jco.24.00176}

}

MLA

Cite this

MLA Copy

MacDonald, Courtney, et al. “Hormonal Contraception and Breast Cancer Risk for Carriers of Germline Mutations in BRCA1 and BRCA2.” Journal of Clinical Oncology, vol. 43, no. 4, Feb. 2025, pp. 422-431. https://ascopubs.org/doi/10.1200/JCO.24.00176.

Publisher

American Society of Clinical Oncology (ASCO)

Journal

Journal of Clinical Oncology

scimago Q1

wos Q1

SJR

11.205

CiteScore

38.9

Impact factor

41.9

ISSN

0732183X (Print)

15277755 (Electronic)

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