Estrogen Metabolism in Women with Breast Cancer

The three dominant oxidative biotransformations of estradiol were examined in 10 normal women and 33 females with breast cancer by using a recently devised radiometric method. Estradiol tracers, labeled with 3H specifically in the 17 alpha, C-2, or 16 alpha position, were used to measure both the rate and extent of 17 beta-ol oxidation (the initial metabolic step) and the subsequent 2- and 16 alpha-oxidative reactions. The mean +/- SEM values for the extent of extradiol metabolism at these three specific sites for the extent of estradiol metabolism at these three specific sites were 76.9 +/- 5.3%, 31.1 +/- 4.0%, and 9.3 +/- 0.8%, respectively in normal subjects. Corresponding data in patients with breast cancer--i.e., 73.0 +/- 4.2%, 32.7 +/- 2.7%, and 14.9 +/- 1.5%--revealed a significantly greater extent of 16 alpha-hydroxylation in the latter population. Because the 16 alpha-hydroxylated compounds (including estriol) are themselves potent estrogens, these changes may have important hyperestrogenic consequences that could have a bearing on the etiology of the disease.