ELEVATED SERUM C-ERBB-2 ANTIGEN LEVELS AND DECREASED RESPONSE TO HORMONE-THERAPY OF BREAST-CANCER

Purpose: Decisions concerning the use of hormone therapy to treat meta static breast cancer are made on the basis of the presence of estrogen receptor (ER). Despite the presence of ER, half of patients will not respond to hormone treatment, The purpose of this study was to determi ne the effect of overexpression of HER-2/neu on the response to hormon e therapy. Patients and Methods: Sera from 300 metastatic breast cance r patients with ER-positive (ER(+)), ER status unknown, or ER(-)/proge sterone receptor positive (PR(+)) randomized to receive second-line ho rmone therapy with either megestrol acetate or fadrozole were evaluate d. An enzyme immunoassay (EIA) specific for the extracellular domain o f the c-erbB-2 (HER-2/neu) oncogene product was used to detect serum l evels. Results: Fifty-eight patients (19.3%) had elevated serum c-erbB -2 protein levels, using a selected cut-point of 30 U/mL. The response rate (complete responses [CRs] plus partial responses [PRs] plus stab le disease [S]) to endocrine therapy was 40.9% in 242 patients with lo w serum c-erbB-2 levels and only 20.7% in 58 patients with elevated se rum c-erbB-2 levels (P = .004). The median duration of treatment respo nse wets longer in the group with low serum c-erbB-2 levels (15.5 mont hs) compared with the group with elevated serum c-erbB-2 levels (11.6 months). Survival was also significantly shorter in patients with elev ated serum c-erbB-2 levels (P < .0001). Conclusion: Patients with ER()/E-erbB-2(+) metastatic breast cancer are less likely to respond to h ormone treatment than ER(+)/c-erbB-2(-) patients. Their survival durat ion is also shorter. (C) 1995 by American Society of Clinical Oncology .