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Urinary Estrogen Metabolites and Mammographic Parenchymal Patterns in Postmenopausal Women¹

Cancer and Public Health Unit, Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London WC1E 7HT, England [E. R., I. d. S. S., B. D. S.]; Department of Hygiene and Epidemiology, University of Athens Medical School, Athens, Greece GR-14561 [E. R., A. L.]; Strang Cornell Cancer Research Laboratory, New York, New York 10021 [H. L. B., D. W. S.]; and First Surgical Clinic, Hygeia Diagnostic Centre of Athens, Athens, Greece GR-14561 [D. L.]

It has been hypothesized that women who metabolize their endogenous estrogens predominantly via 16-hydroxylation rather than via 2-hydroxylation and, as a result, have a low ratio of 2-hydroxyestrone (2-OHE1):16-hydroxyestrone (16-OHE1) are at an increased risk of breast cancer. Epidemiological evidence in support of this hypothesis is scarce and mostly based on measurements made after the onset of the disease. To gain insight into the role of these metabolites in the etiology of breast cancer, we assessed their relationship with high-density Wolfe mammographic parenchymal patterns (P2/DY), a recognized indicator of risk of this tumor. The study was nested within a large cross-sectional survey on determinants of mammographic patterns carried out in a population-based breast screening program in Northern Greece. Urinary levels of 2-OHE1 and 16-OHE1 were measured in a random sample of 70 postmenopausal women with P2/DY mammographic patterns and in a random sample of 70 women with N1 mammographic patterns, individually matched to the P2/DY women on year of birth, years since menopause and date of urine collection. Women with a P2/DY pattern had, on average, 58% higher levels of 2-OHE1 (P = 0.002) and 15% higher levels of 16-OHE1 (P = 0.37) than those with an N1 pattern. The ratio of 2-OHE1:16-OHE1 was 35% higher (P = 0.005) in women with a P2/DY pattern. Women in the highest one-third of this ratio were six times more likely to have a P2/DY pattern than those in the lowest one-third after adjusting for potential confounders (prevalence odds ratio, 6.2; 95% CI, 1.7–22.9; test for linear trend, P = 0.002). These findings seem to suggest that a high, rather than a low, 2-OHE1:16-OHE1 ratio may be associated with an increase in breast cancer risk at postmenopausal ages, unless the pathway through which estrogen metabolites may affect breast cancer risk is unrelated to mammographic parenchymal patterns.

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