MD patterns refer to the distribution of fat, connective, and epithelial tissue in the breast, and are strong predictors of BC risk. A high percentage of dense parenchyma on mammographic images confers a 4.0- to 6.0-fold risk to develop BC (1). Endogenous estrogens (Es) and perhaps As are important in the etiology ofBC (2-4). An association of MDs and hormone levels is supported by several observations. Hormone replacement therapy (HRT) increases MD (5). In the other hand, tamoxifen treatment improves MDs (6) by suppressing ovarian function through a gonadotropin-releasing hormone agonist (7). Moreover, MDs returned to baseline after tamoxifen was discontinued (8). However, two cross-sectional investigations detected no strong relation between MDs and serum E and progesterone (P) levels (9, 10).

Because some metabolites of endogenous Es may have more estrogenic effects than others, we hypothesized that differences in E metabolic pathways may be related to MDs. The metabolism of E2 follows two major competing pathways, C2-and C16a-OH-lation, and a minor C4-OH-lation (11-13). It has been proposed that women who metabolize a larger proportion of their endogenous Es through are at greater BC risk because has genotoxic effects, damages DNA, and enhances breast cell growth, whereas 2-OH-E, inhibits breast cell proliferation. However, before transformation into methoxy compounds by the enzyme catechol methyl transferase (COMT), 2-OH compounds have some estrogenic and growth promoting effects (13). The evidence on the association of the 2/16 ratio with BC is inconsistent (14-18), and a previous study on MDs reported results contrary to the original hypothesis (19). Women in the highest tertile of the 2/16 ratio were 6.0 times more likely to have a high risk mammographic pattern. In disagreement with the hypothesis that women from ethnic groups with lower BC risk have a higher 2/16 ratio, a comparison between Finnish and Asian women (20) reported a higher ratio in Finnish women. Herein, ethnic differences in urinary E, A, and E metabolite levels and their relation with MD were investigated.

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