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A metabolomic analysis of adiposity measures and pre- and postmenopausal breast cancer risk in the Nurses’ Health Studies



Adiposity is consistently positively associated with postmenopausal breast cancer and inversely associated with premenopausal breast cancer risk, though the reasons for this difference remain unclear.


In this nested case–control study of 1649 breast cancer cases and 1649 matched controls from the Nurses’ Health Study (NHS) and the NHSII, we selected lipid and polar metabolites correlated with BMI, waist circumference, weight change since age 18, or derived fat mass, and developed a metabolomic score for each measure using LASSO regression. Logistic regression was used to investigate the association between this score and breast cancer risk, adjusted for risk factors and stratified by menopausal status at blood draw and diagnosis.


Metabolite scores developed among only premenopausal or postmenopausal women were highly correlated with scores developed in all women (r = 0.93–0.96). Higher metabolomic adiposity scores were generally inversely related to breast cancer risk among premenopausal women. Among postmenopausal women, significant positive trends with risk were observed (e.g., metabolomic waist circumference score OR Q4 vs. Q1 = 1.47, 95% CI = 1.03–2.08, P-trend = 0.01).


Though the same metabolites represented adiposity in pre- and postmenopausal women, breast cancer risk associations differed suggesting that metabolic dysregulation may have a differential association with pre- vs. postmenopausal breast cancer.

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Fig. 1: Spearman correlations of metabolites with adiposity measures, by class of metabolite.

Data availability

The data generated in this study are not publicly available due to participant confidentiality and privacy concerns but are available upon request. Further information including the procedures to obtain and access data from the Nurses’ Health Studies is described at


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We would like to thank the participants and staff of the Nurses’ Health Study 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 and WY. The authors assume full responsibility for the analyses and interpretation of these data.


This study was funded by the National Institutes of Health (NIH)/National Cancer Institute (NCI) with the following grants: UM1 CA186107, P01 CA87969, R01 CA49449, R01 CA050385, U01 CA176726, R01 CA67262 and T32 CA009001.

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Authors and Affiliations



KB and AHE designed the study. CC and JA performed metabolomic profiling. KB and OZ performed the statistical analysis. BD, RB, RT, BR and AHE performed interpretation of results. AHE, BR and RT supervised the study. All authors reviewed the manuscript and approved its final version.

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Correspondence to Kristen D. Brantley.

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The authors declare no competing interests.

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The return of the self-administered questionnaires and blood samples were considered to imply consent. 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. The study was performed in accordance with the Declaration of Helsinki.

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Brantley, K.D., Zeleznik, O.A., Dickerman, B.A. et al. A metabolomic analysis of adiposity measures and pre- and postmenopausal breast cancer risk in the Nurses’ Health Studies. Br J Cancer (2022).

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