Cancer Res; 77(4); 1-8
Joshua N. Sampson, Roni T. Falk, Catherine Schairer, Steven C. Moore, Barbara J. Fuhrman, Cher M. Dallal, Doug C. Bauer, Joanne F Dorgan, Xiao-Ou Shu, Wei Zheng, Louise A. Brinton, Mitchell H. Gail, Regina G. Ziegler, Xia Xu, Robert Hoover and Gretchen L. Gierach
DOI: 10.1158/0008-5472.CAN-16-1717 Published 23 December 2016
Abstract
Endogenous estradiol and estrone are linked causally to increased risks of breast cancer. In this study, we evaluated multiple competing hypotheses for how metabolism of these parent estrogens may influence risk. Prediagnostic concentrations of estradiol, estrone, and 13 metabolites were measured in 1298 postmenopausal cases of breast cancer and 1524 matched controls in four separate patient cohorts. Median time between sample collection and diagnosis was 4.4-12.7 years across the cohorts. Estrogen analytes were measured in serum or urine by liquid chromatographic-tandem mass spectrometry. Total estrogen levels (summing all 15 estrogens/estrogen metabolites) were associated strongly and positively with breast cancer risk. Normalizing total estrogen levels, we also found that a relative increase in levels of 2-hydroxylation pathway metabolites, or in the ratio of 2-hydroxylation:16-hydroxylation pathway metabolites, were associated inversely with breast cancer risk. These associations varied by total estrogen levels, with the largest risk reductions occurring in women in the highest tertile. With appropriate validation, these findings suggest opportunities for breast cancer prevention by modifying individual estrogen metabolism profiles through either lifestyle alterations or chemopreventive strategies.
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