Epidemiologic studies of estrogen metabolism and breast cancer

Steroids
Regina G ZieglerCharles E Matthews

Abstract

Early epidemiologic studies of estrogen metabolism measured only 2-hydroxyestrone and 16α-hydroxyestrone and relied on direct enzyme immunoassays without purification steps. Eight breast cancer studies have used these assays with prospectively collected blood or urine samples. Results were inconsistent, and generally not statistically significant; but the assays had limited specificity, especially at the low concentrations characteristic of postmenopausal women. To facilitate continued testing in population-based studies of the multiple laboratory-based hypotheses about the roles of estrogen metabolites, a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed to measure concurrently all 15 estrogens and estrogen metabolites in human serum and urine, as unconjugated and total (glucuronidated+sulfated+unconjugated) concentrations. The assay has high sensitivity (lower limit of quantitation ∼1-2 pmol/L), reproducibility (coefficients of variation generally ⩽5%), and accuracy. Three prospective studies utilizing this comprehensive assay have demonstrated that enhanced 2-hydroxylation of parent estrogens (estrone+estradiol) is associated with reduced risk of postmenopausal breast cancer. In the Prostate...Continue Reading

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