Abnormal oxidative metabolism of estradiol 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 17α, C-2, or 16α position, were used to measure both the rate and extent of 17β-ol oxidation (the initial metabolic step) and the subsequent 2- and 16α-oxidative reactions. The mean ± SEM values 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 16α-hydroxylation in the latter population. Because the 16α-hydroxylated compounds (including estriol) are themseleves potent estrogens, these changes may have important hyperestrogenic consequences that could have a bearing on the etiology of the disease.