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Urinary estrogens and estrogen metabolites and mammographic density in premenopausal women

  • Epidemiology
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Abstract

Mammographic density is a strong and independent risk factor for breast cancer and is considered an intermediate marker of risk. The major predictors of premenopausal mammographic density, however, have yet to be fully elucidated. To test the hypothesis that urinary estrogen metabolism profiles are associated with mammographic density, we conducted a cross-sectional study among 352 premenopausal women in the Nurses’ Health Study II (NHSII). We measured average percent mammographic density using a computer-assisted method. In addition, we assayed 15 estrogens and estrogen metabolites (jointly termed EM) in luteal-phase urine samples. We used multivariable linear regression to quantify the association of average percent density with quartiles of each individual EM as well as the sum of all EM (total EM), EM groups defined by metabolic pathway, and pathway ratios. In multivariable models controlling for body mass index and other predictors of breast density, women in the top quartile of total EM had an average percent density 3.4 percentage points higher than women in the bottom quartile (95 % confidence interval: −1.1, 8.0; p trend = 0.08). A non-significant positive association was noted for the 2-hydroxylation pathway catechols (breast density was 4.0 percentage points higher in top vs. bottom quartile; p trend = 0.06). In general, we observed no associations with parent estrogens or the 4- or 16-hydroxylation pathways or pathway ratios. These results suggest that urinary luteal estrogen profiles are not strongly associated with premenopausal mammographic density. If these profiles are associated with breast cancer risk, they may not act through influences on breast density.

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Acknowledgments

We thank Barbara DeSouza and Divya Prithviraj for their assistance with data collection. This work was supported in part by the Breast Cancer Research Foundation, the National Institutes of Health, National Cancer Institute (NCI) (CA124865, CA67262, and CA50385), the Intramural Research Program of the NCI Division of Cancer Epidemiology and Genetics, and with federal funds of the NCI awarded under Contract HHSN261200800001E to SAIC-Frederick. K.A.B. was supported by the Nutritional Epidemiology of Cancer Training Grant (R25 CA098566). The content of this publication does not necessarily reflect the views or policies of the U.S. Department of Health and Human Services; nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

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 & 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, A. Heather Eliassen, Susan E. Hankinson, Bernard Rosner & Rulla M. Tamimi

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

    Susan E. Hankinson

  4. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA

    Gretchen L. Gierach & Regina G. Ziegler

  5. Laboratory of Proteomics and Analytic Technologies, SAIC-Frederick, Inc., National Cancer Institute at Frederick, Frederick, MD, USA

    Xia Xu

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

    Bernard Rosner

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  1. Kimberly A. Bertrand
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  2. A. Heather Eliassen
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  4. Gretchen L. Gierach
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  5. Xia Xu
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  7. Regina G. Ziegler
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Correspondence to Kimberly A. Bertrand.

Additional information

Regina G. Ziegler, Rulla M. Tamimi—co-last authors.

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Bertrand, K.A., Eliassen, A.H., Hankinson, S.E. et al. Urinary estrogens and estrogen metabolites and mammographic density in premenopausal women. Breast Cancer Res Treat 136, 277–287 (2012). https://doi.org/10.1007/s10549-012-2240-0

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