Influence of circulating c-erbB-2 serum protein on response to adjuvant chemotherapy in node-positive breast cancer patients

This retrospective case control study investigated the therametric value of the circulating c-erbB-2 gene product (Her-2, NEU) as (1) an eligibility criterion for high doses of chemotherapy and (2) response to standard adjuvant chemotherapy in node-positive breast cancer patients. Preoperative c-erbB-2 levels were measured in 211 locally advanced (> 3 nodes positive), pre- and perimenopausal breast cancer patients to determine if circulating levels of the gene product can assist in the determination of appropriate therapeutic options. 152 of 211 breast cancer patients received post-operatively a combination chemotherapy including the anthracycline analog mitoxantrone, while 59 patients were treated with conventional CMF therapy. Using 120 fmol/ml as a cut-off level, elevated c-erbB-2 values were found in 26 (12.3%) patients with locally advanced breast cancer. In univariate analysis significant survival differences were detected when c-erbB-2 'positive' patients were compared with c-erbB-2 'negative' patients. However, no significant survival differences were detected, when c-erbB-2 'positive' patients were compared according to regimen of adjuvant treatment. In multivariate analysis c-erbB-2 was an independent prognostic factor for predicting disease-free survival, but not for overall survival. High levels of c-erbB-2 were associated with low estrogen and progesterone receptor concentrations of the tumor cytosol. There was no correlation between elevated c-erbB-2 values and age, tumor size or degree of nodal involvement. c-erbB-2 was a better predictor of risk of recurrence than extent of nodal involvement or hormone receptor status.