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History of infertility and risk of breast cancer: a prospective cohort study

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

Research on infertility and risk of breast cancer has been conflicting, potentially because many well-established breast cancer risk factors, such as pregnancy history, are strongly correlated with infertility.

Methods

We followed participants in the Nurses’ Health Study II from 1989 to 2015 (n = 103,080) for the development of invasive breast cancer and calculated Hazard Ratios (HR) and 95% confidence intervals (CI) using Cox regression. Participants with a self-reported history of infertility (12 months of trying without conception) were compared to gravid women with no history of infertility. We classified breast cancer by menopausal status and investigated mediation by reproductive factors.

Results

Over 26 years of follow-up, 26,208 (25.4%) women reported a history of infertility, and 3,201 women were newly diagnosed with invasive breast cancer. We observed no association between infertility history and risk of overall breast cancer (HR: 1.05, 95% CI: 0.97–1.14) or premenopausal breast cancer (RR: 0.93, 95% CI: 0.83–1.03). However, we observed a modest association between history of infertility and risk of postmenopausal breast cancer (HR: 1.13, 95% CI: 1.00–1.28), approximately 50% of which could be attributed to lower total parity and later age at first birth (95% CI: 8.2%–91.0%).

Conclusions

Women with a history of infertility were at increased risk of postmenopausal breast cancer. Older age at first birth and lower total parity explained approximately half of the association between infertility and risk of postmenopausal breast cancer.

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Data availability

The data underlying this article cannot be shared publicly due to participant confidentiality and privacy concerns. Further information including the procedures to obtain and access data from the Nurses’ Health Studies is described at https://www.nurseshealthstudy.org/researchers (contact email: nhsaccess@channing.harvard.edu).

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Acknowledgements

We would like to thank participants in the Nurses’ Health Study cohorts and Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital as home of the Nurses' Health Study II. The authors would like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention’s National Program of Cancer Registries (NPCR) and/or the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program. Central registries may also be supported by state agencies, universities, and cancer centers. Participating central cancer registries include the following: Alabama, Alaska, Arizona, Arkansas, California, Delaware, Colorado, Connecticut, Florida, Georgia, Hawaii, Idaho, Indiana, Iowa, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Mississippi, Montana, Nebraska, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Puerto Rico, Rhode Island, Seattle SEER Registry, South Carolina, Tennessee, Texas, Utah, Virginia, West Virginia, Wyoming.

Funding

This work was supported by grants HD096033 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, U01 CA176726, U01 HL145386.

Author information

Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, 1295 N. Martin Ave, Tucson, AZ, 85724, USA

    Leslie V. Farland

  2. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Siwen Wang, Jorge E. Chavarro & Yi-Xin Wang

  3. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Janet W. Rich-Edwards, Jorge E. Chavarro & Stacey A. Missmer

  4. Division of Women’s Health, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Janet W. Rich-Edwards

  5. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA

    Audrey J. Gaskins

  6. Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Jorge E. Chavarro

  7. Department of Population Health Sciences, Weill Cornell College of Medicine, NewYork, NY, USA

    Rulla M. Tamimi

  8. Department of Obstetrics and Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI, USA

    Stacey A. Missmer

  9. University of Arizona Cancer Center, University of Arizona, Tucson, USA

    Leslie V. Farland

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  1. Leslie V. Farland
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Contributions

LVF, SAM, RMT conceived, designed, and supervised the study. SW performed the statistical analysis. LVF, YW, AJG, JWRE, SW, JEC, RMT, and SAM drafted and critically reviewed the manuscript and approved the final version.

Corresponding author

Correspondence to Leslie V. Farland.

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Conflict of interest

The authors have nothing to disclose.

Ethical approval

The study protocol was approved by the institutional review boards of the Brigham and Women’s Hospital and Harvard T.H. Chan School of Public Health, and those of participating registries as required. Return of completed questionnaires implied consent to participate in the study.

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Farland, L.V., Wang, S., Rich-Edwards, J.W. et al. History of infertility and risk of breast cancer: a prospective cohort study. Breast Cancer Res Treat 199, 185–193 (2023). https://doi.org/10.1007/s10549-023-06907-1

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  • DOI: https://doi.org/10.1007/s10549-023-06907-1

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