Relation of Serum Estrogen Metabolites with Terminal Duct Lobular Unit Involution Among Women Undergoing Diagnostic Image-Guided Breast Biopsy

Hannah Oh, Zeina G. Khodr, Mark E. Sherman, Maya Palakal, Ruth M. Pfeiffer, Laura Linville, Berta M. Geller, Pamela M. Vacek, Donald L. Weaver, Rachael E. Chicoine, Roni T. Falk, Hisani N. Horne, Daphne Papathomas, Deesha A. Patel, Jackie Xiang, Xia Xu, Timothy Veenstra, Stephen M. Hewitt, John A. Shepherd, Louise A. BrintonJonine D. Figueroa, Gretchen L. Gierach

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


Higher levels of circulating estrogens and estrogen metabolites (EMs) have been associated with higher breast cancer risk. In breast tissues, reduced levels of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini per TDLU, have also been linked to elevated breast cancer risk. However, it is unknown whether reduced TDLU involution mediates the risk associated with circulating EMs. In a cross-sectional analysis of 94 premenopausal and 92 postmenopausal women referred for clinical breast biopsy at an academic facility in Vermont, we examined the associations of 15 EMs, quantified using liquid chromatography-tandem mass spectrometry, with the number of TDLUs and acini count/TDLU using zero-inflated Poisson regression with a robust variance estimator and ordinal logistic regression models, respectively. All analyses were stratified by menopausal status and adjusted for potential confounders. Among premenopausal women, comparing the highest vs. the lowest tertiles, levels of unconjugated estradiol (risk ratio (RR) = 1.74, 95 % confidence interval (CI) = 1.06–2.87, p trend = 0.03), 2-hydroxyestrone (RR = 1.74, 95 % CI = 1.01–3.01, p trend = 0.04), and 4-hydroxyestrone (RR = 1.74, 95 % CI = 0.99–3.06, p trend = 0.04) were associated with significantly higher TDLU count. Among postmenopausal women, higher levels of estradiol (RR = 2.09, 95 % CI = 1.01–4.30, p trend = 0.04) and 16α-hydroxyestrone (RR = 2.27, 95 % CI = 1.29–3.99, p trend = 0.02) were significantly associated with higher TDLU count. Among postmenopausal women, higher levels of EMs, specifically conjugated estrone and 2- and 4-pathway catechols, were also associated with higher acini count/TDLU. Our data suggest that higher levels of serum EMs are generally associated with lower levels of TDLU involution.

Original languageEnglish
Pages (from-to)305-315
Number of pages11
JournalHormones and Cancer
Issue number5-6
Publication statusPublished - 2016 Dec 1
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics of the National Cancer Institute. Breast Cancer Research Stamp Funds (MES, LAB) and cooperative agreement U01CA70013 (BMG, PMV, DLW, REC) from the National Cancer Institute funded some of the data collection for this study. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

Publisher Copyright:
© 2016, Springer Science+Business Media New York (outside the USA).

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cancer Research


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