Urinary estrogen metabolites and mammographic parenchymal patterns in postmenopausal women

It has been hypothesized that women who metabolize their endogenous estroge ns predominantly via 16(alpha)- hydroxylation rather than via 2-hydroxylati on and, as a result, have a low ratio of 2-hydroxyestrone (2-OHE1): 16(alph a)-hydroxyestrone (16(alpha)-OHE1) are at an increased risk of breast cance r. Epidemiological evidence in support of this hypothesis is scarce and mos tly based on measurements made after the onset of the disease. To gain insi ght into the role of these metabolites in the etiology of breast cancer, we assessed their relationship with high-density Wolfe mammographic parenchym al patterns (P2/DY), a recognized indicator of risk of this tumor. The stud y was nested within a large cross-sectional survey on determinants of mammo graphic patterns carried out in a population-based breast screening program in Northern Greece. Urinary levels of 2-OHE1 and 16(alpha)-OHE1 were measu red in a random sample of 70 postmenopausal women with P2/DY mammographic p atterns and in a random sample of 70 women with N1 mammographic patterns, i ndividually matched to the P2/DY women on year of birth, years since menopa use and date of urine collection. Women with a P2/DY pattern had, on averag e, 58% higher levels of 2-OHE1 (P = 0.002) and 15% higher levels of 16(alph a)- OHE1 (P = 0.37) than those with an N1 pattern. The ratio of 2-OHE1:16(a lpha)-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 poten tial confounders (prevalence odds ratio, 6.2; 95% CI, 1.7-22.9; test for li near trend, P = 0.002). These findings seem to suggest that a high, rather than a low, 2-OHE1:16(alpha)-OHE1 ratio may be associated with an increase in breast cancer risk at postmenopausal ages, unless the pathway through wh ich estrogen metabolites may affect breast cancer risk is unrelated to mamm ographic parenchymal patterns.