A pilot study of urinary estrogen metabolites (16 alpha-OHE1 and 2-OHE1) in postmenopausal women with and without breast cancer

The two main pathways for metabolizing estrogen are via 16 alpha-hydroxylation and 2-hydroxylation. The 16 alpha-hydroxy metabolites are biologically active; the 2-hydroxy metabolites are not. It is suggested that women who metabolize a larger proportion of their endogenous estrogen via the 16 alpha-hydroxy pathway may be al significantly elevated risk of breast cancer compared with women who metabolize proportionally more estrogen via the 2-hydroxy pathway. In particular, it is suggested that the ratio of urinary 2-hydroxyestrone (2-OHE1) to 16 alpha-hydroxyestrone (16 alpha-OHE1) is an index of reduced breast cancer risk. This pilot study compared this ratio in postmenopausal women diagnosed with breast cancer to those of healthy controls. Urinary concentrations of estrone (E-1), 17 beta-estradiol (E-2) and estriol (E-3) were also quantified. White women who were subjects in a previous breast cancer case-control study at our institution were eligible for inclusion. All participants provided a sample of their first morning urine. The results from the first 25 cases and 23 controls are presented here. The ratio of 2-OHE1 to 16 alpha-OHE1 was 12% lower in the cases (p = 0.58). However, urinary E-1 was 30% higher (p = 0.10), E-2 was 58% higher (p = 0.07), E-3 was 15% higher (p = 0.48), and the sum of E-1, E-2, and E-3 was 22% higher (p = 0.16) in the cases. These preliminary results do not support the hypothesis that the ratio of the two hydroxylation metabolites (2-OHE1/16 alpha-OHE1) is an important risk factor for breast cancer or that it is a better predictor of breast cancer risk than levels of E-1, E-2 and E-3 measured in urine.