Urinary 2-hydroxyestrone/16α-hydroxyestrone ratio and risk of breast cancer in postmenopausal women

Background: It has been suggested that women who metabolize a larger proportion of their endogenous estrogen via the 16 alpha-hydroxylation pathway may be at elevated risk of breast cancer compared with women who metabolize proportionally more estrogen via the 2-hydroxylation pathway. However, the supporting epidemiologic data are scant. Consequently, we compared the ratio of urinary 2-hydroxyestrone (2-OHE1) to 16 alpha-hydroxyestrone (16 alpha-OHE1) in postmenopausal women with breast cancer and in healthy control subjects. Methods: Estrogen metabolites were measured in urine samples obtained from white women who had participated in a previous population-based, breast cancer case-control study at our institution. All P values are from two-sided tests. Results: All of the urinary estrogens measured, with the exception of estriol, were higher in the 66 case patients than in the 76 control subjects, The mean value of urinary 2-OHE1 in case patients was 13.8% (P = .20) higher than that in control subjects, 16 alpha-OHE1, was 12.1% (P = .23) higher, estrone was 20.9% higher (P = .14), and 17 beta-estradiol was 12.0% higher (P = .36), The ratio of 2-OHE1 to 16 alpha-OHE1 was 1.1% higher in the patients (P = .84), contrary to the hypothesis. Compared with women in the lowest third of the values for the ratio of urinary 2-OHE1 to 16 alpha-OHE1, women in the highest third were at a nonstatistically significantly increased risk of breast cancer (odds ratio = 1.13; 95% confidence interval = 0.46-2.78), again contrary to the hypothesis. Conclusion: This study does not support the hypothesis that the ratio of the two hydroxylated metabolites (2-OHE1/16 alpha-OHE1) is an important risk factor for breast cancer.