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 metastatic 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 determine the effect of overexpression of HER-2/neu on the response to hormone therapy. Patients and Methods: Sera from 300 metastatic breast cancer patients with ER-positive (ER(+)), ER status unknown, or ER(-)/progesterone receptor positive (PR(+)) randomized to receive second-line hormone therapy with either megestrol acetate or fadrozole were evaluated. An enzyme immunoassay (EIA) specific for the extracellular domain of the c-erbB-2 (HER-2/neu) oncogene product was used to detect serum levels. 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 stable disease [S]) to endocrine therapy was 40.9% in 242 patients with low serum c-erbB-2 levels and only 20.7% in 58 patients with elevated serum c-erbB-2 levels (P = .004). The median duration of treatment response wets longer in the group with low serum c-erbB-2 levels (15.5 months) compared with the group with elevated serum c-erbB-2 levels (11.6 months). Survival was also significantly shorter in patients with elevated serum c-erbB-2 levels (P < .0001). Conclusion: Patients with ER(+)/E-erbB-2(+) metastatic breast cancer are less likely to respond to hormone treatment than ER(+)/c-erbB-2(-) patients. Their survival duration is also shorter. (C) 1995 by American Society of Clinical Oncology.