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Premenopausal plasma 25-hydroxyvitamin D, mammographic density, and risk of breast cancer

  • Epidemiology
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Abstract

Epidemiologic evidence for an association between plasma 25-hydroxyvitamin D [25(OH)D] and breast cancer is inconsistent. Data are especially limited for premenopausal women and for associations with mammographic density. To test the hypothesis that plasma concentration of 25(OH)D is associated with mammographic density, we conducted a cross-sectional study among 835 premenopausal women in the Nurses’ Health Studies. We measured 25(OH)D in blood samples and used multivariable linear regression to quantify the association of average percent density by quartile of plasma 25(OH)D. In a nested case-control analysis including 493 breast cancer cases, we evaluated risk of breast cancer associated with vitamin D status within tertiles of mammographic density. Women in the top quartile of plasma 25(OH)D levels had an average percent breast density 5.2 percentage points higher than women in the bottom quartile (95 % confidence interval: 1.8, 8.7; P trend <0.01), after adjusting for predictors of 25(OH)D and established breast cancer risk factors. Plasma 25(OH)D concentration was significantly inversely associated with breast cancer risk among women with high mammographic density (P trend < 0.01) but not among women in lower tertiles of mammographic density (P-interaction < 0.01). These results do not support the hypothesis that vitamin D is inversely associated with percent mammographic density in premenopausal women. There was evidence that the association between premenopausal 25(OH)D and breast cancer risk varies by mammographic density, with an inverse association apparent only among women with high mammographic density.

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Acknowledgments

We thank Barbara DeSouza and Divya Prithviraj for their assistance with data collection and analysis. We would also like to thank the participants and staff of the Nurses Health Studies’ for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data. This work was supported in part by the Breast Cancer Research Foundation and the National Institutes of Health (CA124865, CA87969, CA49449, CA67262, CA50385, CA176726, and CA131332). K.A.B. was supported by the Nutritional Epidemiology of Cancer Training Grant (R25 CA098566) and the Simeon J. Fortin Charitable Foundation, Bank of America, N.A., Co-Trustee.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA

    Kimberly A. Bertrand, Susan E. Hankinson, Walter Willett & Rulla M. Tamimi

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

    Kimberly A. Bertrand, Bernard Rosner, A. Heather Eliassen, Susan E. Hankinson, Walter Willett & Rulla M. Tamimi

  3. Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA

    Bernard Rosner

  4. Division of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA

    Susan E. Hankinson

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

    Kathryn M. Rexrode

  6. Department of Nutrition, Harvard School of Public Health, Boston, MA, USA

    Walter Willett

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  1. Kimberly A. Bertrand
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  2. Bernard Rosner
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  3. A. Heather Eliassen
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  4. Susan E. Hankinson
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Correspondence to Kimberly A. Bertrand.

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Bertrand, K.A., Rosner, B., Eliassen, A.H. et al. Premenopausal plasma 25-hydroxyvitamin D, mammographic density, and risk of breast cancer. Breast Cancer Res Treat 149, 479–487 (2015). https://doi.org/10.1007/s10549-014-3247-5

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