Biological and clinical relevance of Kd values for estradiol binding in primary breast cancer tumors.
The question of whether the dissociation constant (Kd) observed for the binding between estradiol and the [3H]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 (greater than or equal to 10 fmol/mg cytosol protein) primary breast cancer patients. The median value for Kds was found to be 0.9 X 10(-10) M. Kd values were only weakly correlated to ER concentrations in the respective biopsies. Nevertheless, high Kd 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 Kd value. In contrast, the frequency of PgR-positivity is significantly lower among postmenopausal patients with high Kd values. Furthermore, postmenopausal patients with high Kd values (greater than 1.4 X 10(-10) M) tend to have shorter recurrence-free survivals than other ER-positive patients. A possible interpretation of these findings is that high Kd 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 Kd values might reflect the presence of an estradiol binding molecule(s) slightly different from normal ER in the tissue of postmenopausal patients.
Thorpe
S M
SM
University Department of Clinical Physiology and Nuclear Medicine, Finsen Institute, Rigshospitalet, Copenhagen, Denmark.
Rose
C
C
D001943:Breast Neoplasms / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006801:Humans; D008593:Menopause / Q000378:metabolism; D008875:Middle Aged; D011959:Receptors, Estradiol / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000032:analysis
D011959:Receptors, Estradiol; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D004958:Estradiol