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Circulating lipids, mammographic density, and risk of breast cancer in the Nurses’ Health Study and Nurses’ Health Study II

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Epidemiologic evidence supports an association between high mammographic density and increased breast cancer risk yet etiologic mechanisms remain largely unknown. Mixed evidence exists as to whether circulating lipid levels influence mammographic density and breast cancer risk. Therefore, we examined these associations in the Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHSII), two large prospective cohorts with information on PMD and circulating lipid measures, long follow-up, and breast cancer risk factor and outcome data.


We conducted a nested case–control study among women in the NHS and NHSII. Percent mammographic density (PMD) was measured using Cumulus software, a computer-assisted method, on digitized film mammograms. Cross-sectional associations between circulating lipids [total cholesterol (n = 1,502), high-density lipoprotein (HDL-C; n = 579), and triglycerides (n = 655)] and PMD were evaluated among controls. All analyses were stratified by menopausal status at time of mammogram. Relative risks for breast cancer by lipid and PMD measures were estimated among postmenopausal women in the full nested case–control study (cases/controls for cholesterol, HDL-C, and triglycerides were 937/975, 416/449, and 506/537, respectively).


There were no significant associations between circulating lipid levels and PMD among healthy women, irrespective of menopausal status. The association between PMD and breast cancer risk among postmenopausal women was not modified by circulating lipid levels (p interaction = 0.83, 0.80, and 0.34 for total cholesterol, HDL-C, and triglycerides, respectively).


Overall, no association was observed between lipid levels and PMD, and there was no evidence that lipid levels modified the association between PMD and breast cancer risk.

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We would 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 study was supported by research grants from the National Cancer Institute, National Institutes of Health, UM1 CA186107, UM1 CA176726, CA175080, CA124865, CA131332, R01 CA67262, P01 CA87969, R01 CA49449, Avon Foundation for Women, Susan G. Komen for the Cure®, and Breast Cancer Research Foundation. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Correspondence to Sarah A. Lucht.

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Dr. Borgquist reports receiving consultant fees and research support from Novartis and Roche. No conflict of interest was disclosed by the other authors.

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Lucht, S.A., Eliassen, A.H., Bertrand, K.A. et al. Circulating lipids, mammographic density, and risk of breast cancer in the Nurses’ Health Study and Nurses’ Health Study II. Cancer Causes Control 30, 943–953 (2019).

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