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Epidemiology

Birthweight, height, and body mass index in relation to the expression of stem cell markers among women with benign breast biopsies in the Nurses’ Health Study II

British Journal of Cancer volume 133, pages 1695–1707 (2025)Cite this article

Subjects

Abstract

Background

The amount and activity of breast stem cell population may play an important role in breast carcinogenesis. However, little is known about whether early-life and adult anthropometric measures, including body mass index (BMI), birthweight, and height, are associated with stem cell marker expressions in non-cancerous breast tissue.

Methods

Among 730 women with biopsy-confirmed benign breast disease (BBD) in the Nurses’ Health Study II, we quantified immunohistochemical staining of stem cell markers (CD44, CD24, ALDH1A1) in histopathologically normal epithelial and stromal breast tissue. Linear regression was conducted to estimate the associations of anthropometric measures with stem cell marker expression, adjusting for potential confounders.

Results

BMI at age 18 (≥23.0 vs. <19.0 kg/m2), BMI at benign breast biopsy (≥30.0 vs. <21.0 kg/m2), and change in BMI since age 18 (>7.0 vs. ≤0 kg/m2) were inversely associated with CD44 expression levels in epithelium and stroma combined (β [95% CI]= -0.30 [-0.55, -0.04]; -0.34 [−0.59, −0.08]; −0.38 [−0.65, −0.10]; respectively). Change in BMI since age 18 (>7.0 vs. ≤0 kg/m2) was also inversely associated with ALDH1A1 expression in epithelium (−0.31 [−0.62, −0.001]) and stroma (−0.63 [−1.18, −0.08]). Birthweight and height were not associated.

Conclusion

Adiposity measures may be associated with stem cell marker expression among cancer-free women.

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Data availability

The datasets generated and/or analysed during the current study are available in the Nurses’ Health Study repository after reasonable request.

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Acknowledgements

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 centres. Participating central cancer registries include the following: Alabama, Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Hawaii, Idaho, Indiana, Iowa, Kentucky, Louisiana, Massachusetts, Maine, Maryland, 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 the National Cancer Institute at the National Institutes of Health [CA240341 to LY, CA131332, CA175080 to RMT, P01 CA87969, UM1 CA186107, U01 CA176726], Avon Foundation for Women, Susan G. Komen for the Cure®, and Breast Cancer Research Foundation. HO was supported by the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea (NRF) grant (NRF-2023S1A5C2A03095169).

Author information

Author notes

  1. These authors contributed equally: Lusine Yaghjyan, Rulla M. Tamimi.

Authors and Affiliations

  1. Department of Health Policy and Management, Korea University, Seoul, South Korea

    Hannah Oh

  2. Interdisciplinary Program in Precision Public Health, Department of Public Health Sciences, Korea University, Seoul, South Korea

    Hannah Oh

  3. Department of Epidemiology, College of Public Health and Health Professions and College of Medicine, University of Florida, Gainesville, FL, USA

    Lusine Yaghjyan

  4. Department of Pathology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Yujing J. Heng, Gabrielle M. Baker & Brian R. Sardella

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

    Matt B. Mahoney, Divya Murthy & Bernard Rosner

  6. Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA

    Rulla M. Tamimi

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Contributions

HO performed statistical analyses, drafted the manuscript, and interpreted results. LY conceived of and designed the study, made substantial contributions to interpretation of data and critical revision of the manuscript, provided final review and approval, and supervised the overall study progress. YJH assessed laboratory (immunohistochemistry) results and made substantial contributions to interpretation of data and critical revision of the manuscript. GMB made substantial contributions to interpretation of data and critical revision of the manuscript. BRS made substantial contributions to interpretation of data and critical revision of the manuscript. MBM made substantial contributions to interpretation of data and critical revision of the manuscript. DM made substantial contributions to curation of data and critical revision of the manuscript. BR made substantial contributions to interpretation of data and critical revision of the manuscript. RMT conceived of and designed the study, made substantial contributions to interpretation of data and critical revision of the manuscript, and provided final review and approval. LY and RMT shared senior authorship on this manuscript. All authors read and approved the final manuscript.

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Correspondence to Hannah Oh.

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Oh, H., Yaghjyan, L., Heng, Y.J. et al. Birthweight, height, and body mass index in relation to the expression of stem cell markers among women with benign breast biopsies in the Nurses’ Health Study II. Br J Cancer 133, 1695–1707 (2025). https://doi.org/10.1038/s41416-025-03194-z

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