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
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
, 9609 Medical Center Dr., Rm. 7E220, Bethesda, MD, 20892, USA.
Horm Cancer. 2016 Dec;7(5-6):305-315. doi: 10.1007/s12672-016-0265-2. Epub 2016 May 2.
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.
循环雌激素和雌激素代谢产物（EMs）水平升高与乳腺癌风险增加相关。在乳腺组织中，终末导管小叶单位（TDLU）退化水平降低，表现为每个TDLU中TDLU和腺泡数量增加，这也与乳腺癌风险升高有关。然而，尚不清楚TDLU退化减少是否介导了与循环EMs相关的风险。在佛蒙特州一家学术机构对94名绝经前和92名绝经后妇女进行临床乳腺活检的横断面分析中，我们分别使用具有稳健方差估计器的零膨胀泊松回归和有序逻辑回归模型，研究了15种通过液相色谱 - 串联质谱法定量的EMs与TDLU数量以及腺泡计数/TDLU之间的关联。所有分析均按绝经状态分层，并对潜在混杂因素进行了调整。在绝经前妇女中，比较最高三分位数与最低三分位数，未结合雌二醇水平（风险比（RR）=1.74，95%置信区间（CI）=1.06 - 2.87，p趋势=0.03）、2 - 羟雌酮（RR = 1.74，95% CI = 1.01 - 3.01，p趋势=0.04）和4 - 羟雌酮（RR = 1.74，95% CI = 0.99 - 3.06，p趋势=0.04）与TDLU计数显著升高相关。在绝经后妇女中，雌二醇水平升高（RR = 2.09，95% CI = 1.01 - 4.30，p趋势=0.04）和16α - 羟雌酮（RR = 2.27，95% CI = 1.29 - 3.99，p趋势=0.02）与TDLU计数显著相关。在绝经后妇女中，EMs水平升高，特别是结合雌酮以及2 - 和4 - 途径儿茶酚，也与腺泡计数/TDLU升高相关。我们的数据表明，血清EMs水平升高通常与TDLU退化水平降低相关。
