Biological and clinical relevance of K d values for estradiol binding in primary breast cancer tumors

Abstract

The question of whether the dissociation constant ( K d) observed for the binding between eastradiol and the [ 3 H]estrogen receptor (ER) indicates the existence of a single class of estrogen binding proteins in breast cancer tissue has been examined among a population of 3020 ER-positive (⩾ 10 fmol/mg cytosol protein) primary breast cancer patients. The median value for K d s was found to be 0.9 × 10 −10 M . K d values were only weakly correlated to ER concentrations in the respective biopsies. Nevertheless, high K d values were associated with lower measured ER concentrations among pre/perimenopausal patients. Meanwhile, the frequencies of PgR-positivity are consistently high among pre/perimenopausal patients irrespective of K d value. In contrast, the frequency of PgR-positivity is significantly lower among postmenopausal patients with high K d values. Furthermore, postmenopausal patients with high K d values (> 1.4 × 10 −10 M) tend to have shorter recurrence-free survivals than other ER-positive patients. A possible interpretation of these findings is that high K d values reflect physiologically normal, cyclically high endogenous concentrations of estradiol in tumor tissue among pre/perimenopausal patients. Among the postmenopausal patients, the presence of high K d values might reflect the presence of an estradiol binding molecule(s) slightly different from normal ER in the tissue of postmenopausal patients.