Association of Estrogen Metabolism with Breast Cancer Risk in Different Cohorts of Postmenopausal Women
Menée à partir de données de 4 cohortes portant sur 1 298 patientes atteintes d'un cancer du sein après la ménopause et sur 1 524 témoins, cette étude évalue l'association entre le niveau d'estrone, d'estradiol et de 13 métabolites des œstrogènes, mesuré avant le diagnostic, et le risque de développer ultérieurement la maladie
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.%U
Cancer Research 2016