Infertility and breast cancer risk: the complex association in postmenopausal women

From the Harris research group, Public Health Sciences Division

In the vast landscape of breast cancer research, understanding the multifaceted risk factors contributing to its development is crucial. Some of the risk factors that may contribute to an increased risk of developing breast cancer include genetic mutations, age, alcohol use, and physical inactivity. Among these, infertility—a condition experienced by a significant portion of women globally—has emerged as a reproductive risk factor for breast cancer. The relationship is complex, intersecting with factors such as nulliparity (the condition of never having given birth to a child), the number of pregnancies, and age at first pregnancy. New research led by Dr. Holly Harris, an Associate Professor in the Public Health Sciences Division at Fred Hutch, and published in Breast Cancer Research and Treatment, explores this complexity to advise future healthcare recommendations and enlighten millions of women concerning their health risks.

The study examined data from 131,784 postmenopausal women from the Women's Health Initiative (WHI) study, including 23,406 with a history of infertility. In this study infertility was defined as trying to become for more than one year without becoming pregnant. Therefore, the history of infertility should be seen as a condition that can be temporary and can change over time. This study estimated the risk of developing breast cancer in postmenopausal women associated with infertility, adjusting for multiple factors that potentially influence breast cancer risk such as age, reproductive history, and lifestyle choices, identifying a modest yet significant association between infertility and heightened risk of postmenopausal breast cancer. Age at first birth further strongly influenced the association, therefore signifying a complicated interplay between infertility and timing of reproduction in breast cancer risk elevation. Dr. Harris commented on the importance: "This is an important finding because it adds another piece to the jigsaw of how different reproductive factors interrelate with each other across the course of a person's life and affect breast cancer risk."

breast cancer risk." Dr. Harris said their findings were important because "most prior studies of breast cancer and infertility were limited by short follow-up periods, focusing more on premenopausal breast cancer.” She goes on to emphasize that, “Our study is different in that it extends to focus on postmenopausal breast cancer, which makes up the vast majority of diagnoses, and also examines the impact of infertility on breast cancer risk independent of in vitro fertilization (IVF) treatments." This difference determines many unanswered questions and provides some understanding of how infertility, on its own and not through IVF treatments, results in an increased risk of breast cancer.

Dr. Harris said their findings were important because "most prior studies of breast cancer and infertility were limited by short follow-up periods, focusing more on premenopausal breast cancer.” She goes on to emphasize that, “Our study is different in that it extends to focus on postmenopausal breast cancer, which makes up the vast majority of diagnoses, and also examines the impact of infertility on breast cancer risk independent of in vitro fertilization (IVF) treatments." This difference determines many unanswered questions and provides some understanding of how infertility, on its own and not through IVF treatments, results in an increased risk of breast cancer.

However, the study's insights come with an acknowledgment of its limitations, which are instrumental in charting the course for future research. The reliance on self-reported data on infertility could introduce non-differential misclassification, challenging the precision in defining and understanding infertility's causes. Additionally, the generalizability of the findings is constrained by the demographics of the study's participants, who predominantly represent a healthier demographic with a higher socio-economic status than the general U.S. population. Such nuances could potentially skew the detection rates of postmenopausal breast cancer and reported rates of infertility, underlining the need for future studies to encompass a more diverse array of populations. This approach would enable a more comprehensive exploration of how ethnicity and socio-economic disparities in healthcare access impact both infertility and breast cancer screening outcomes.

This study not only underscores the significance of incorporating detailed reproductive histories, including infertility, into breast cancer risk assessments but also advocates for enhanced focus on early reproductive health as a pivotal factor in breast cancer risk management. It beckons further investigation into the subtle dynamics of infertility and other reproductive factors in relation to breast cancer risk, aiming for advancements in prevention strategies and support mechanisms for women worldwide. As the medical community continues to unravel the complex relationship between reproductive history and cancer risk, research endeavors like this one are invaluable in advancing our collective knowledge and fostering improved health outcomes for women across the globe.

The WHI is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services.

Fred Hutch/University of Washington/Seattle Children’s Cancer Consortium Member Dr. Holly Harris contributed to this study.

 

Farland, L. V., Lind, K. E., Thomson, C. A., Saquib, N., Shadyab, A. H., Schnatz, P. F., Robles-Morales, R., Qi, L., Strickler, H., Lane, D. S., Murugappan, G., Roe, D. J., & Harris, H. R. (2024). Infertility and risk of postmenopausal breast cancer in the women's health initiative. Breast cancer research and treatment, 10.1007/s10549-024-07257-2. Advance online publication.