MENOPAUSAL INFLUENCE ON EXPRESSION OF EPIDERMAL GROWTH-FACTOR RECEPTORS, HER-S NEU ONCOPROTEIN, AND CATHEPSIN-D IN BREAST-CANCER/

Identification of patients with lymph node-negative breast cancer at h igh risk for early relapse appears related to expression of epidermal growth factor receptors (EGFR), HER-2/neu oncoprotein, and cathepsin D in tumor biopsies. We evaluated estrogen dependence of these markers by examining their levels as a function of menopausal status. EGFR was determined by an [I-125] epidermal growth factor (EGF) competitive bi nding assay and expressed as fmol/mg membrane protein. HER-2/neu oncop rotein and cathepsin D were measured by EIA and expressed as U/mg extr act protein and pmol/mg cytosol protein, respectively. EGF receptors w ere tested in biopsies from 173 pre- and 91 postmenopausal patients; n o significant difference was observed. K-d values were also comparable . Thirty-nine percent of premenopausal and 29% of postmenopausal patie nts had EGF receptors > 30 fmol/mg indicating overexpression. HER-2/ne u oncoprotein ranged from 10 to 2203 for pre- (n = 293) and from 10 to 3360 U/mg extract protein for postmenopausal patients (n = 134) with medians of 136 and 162, respectively. Again, menopausal status did not appear to influence expression. Thirty-five percent of premenopausal and 41% of postmenopausal patients had tumors overexpressing HER-2/neu oncoprotein using cutoff value of 200 U/mg. Cathepsin D had virtually identical median values in premenopausal (n 469, median = 49 mol/mg) and postmenopausal patients (n = 257, median = 48); 67% of biopsies fr om premenopausal and 63% from postmenopausal women overexpressed cathe psin D. These data indicate that menopausal status does not affect exp ression of these putative prognostic factors in human breast cancer.