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

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...

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Published in:Hormones & cancer 2016-12, Vol.7 (5-6), p.305-315
Main Authors: Oh, Hannah, Khodr, Zeina G., Sherman, Mark E., Palakal, Maya, Pfeiffer, Ruth M., Linville, Laura, Geller, Berta M., Vacek, Pamela M., Weaver, Donald L., Chicoine, Rachael E., Falk, Roni T., Horne, Hisani N., Papathomas, Daphne, Patel, Deesha A., Xiang, Jackie, Xu, Xia, Veenstra, Timothy, Hewitt, Stephen M., Shepherd, John A., Brinton, Louise A., Figueroa, Jonine D., Gierach, Gretchen L.
Format: Article
Language:English
Subjects:
Adult
Breast - metabolism
Breast - pathology
Breast Neoplasms - diagnosis
Breast Neoplasms - metabolism
Cell Biology
Chromatography, Liquid
Cross-Sectional Studies
Endocrinology
Estradiol - blood
Estradiol - isolation & purification
Female
Humans
Hydroxyestrones - blood
Hydroxyestrones - isolation & purification
Image-Guided Biopsy
Internal Medicine
Medicine
Medicine & Public Health
Microbiology
Middle Aged
Oncology
Original Paper
Postmenopause - blood
Premenopause - blood
Systems Biology
Tandem Mass Spectrometry
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Summary: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.
ISSN:1868-8497
1868-8500
DOI:10.1007/s12672-016-0265-2