PLASMA C-ERBB-2 LEVELS IN BREAST-CANCER PATIENTS - PROGNOSTIC-SIGNIFICANCE IN PREDICTING RESPONSE TO CHEMOTHERAPY

Purpose: to determine the significance of plasma c-erbB-2 levels to as sess the extent of disease spread and to predict the response to chemo therapy in node-positive breast cancer patients. Methods: We determine d plasma levels of c-erbB-2 in 79 stages II and III breast cancer pati ents who received cyclophosphamide, methotrexate, and flourouracil (CM F)/cyclophosphamide, methotrexate, flourouracil, vincristine, and pred nisone (CMFVP) chemotherapy. All patients had a minimum follow-up of g reater than 60 months or until disease recurrence. plasma samples were obtained before and after chemotherapy. Plasma c-erbB-2 levels were q uantified by enzyme-linked immunoassay. c-erbB-2 levels were analyzed in relation to the patients' axillary lymph node status, menopausal st atus, disease status, disease-free survival (DFS), and steroid recepto r status of tumor. Results: Plasma c-erbB-2 levels varied widely in br east cancer patients. In general, when all patients were included in t he analyses, plasma c-erbB-2 levels before chemotherapy correlated sig nificantly with the number of positive axillary lymph nodes and with p ostchemotherapy c-erbB-2 levels. No association wets observed between pre- or postchemotherapy c-erbB-2 levels and other variables (patients ' age at diagnosis, receptor status of the tumor, or disease status). The prognostic significance of different factors (ie, nodal status [on e to three v > three positive nodes], menopausal status [pre- v postme nopausal women], estrogen receptor [ER] status [ER + v ER -], and pre- and postchemotherapy c-erbB-2 levels) in predicting DFS was determine d in all study patients. Among the variables examined, nodal status wa s the strangest predictor of DFS in these patients. The second most si gnificant prognostic marker was postchemotherapy c-erbB-2 level. Prech emotherapy c-erbB-2 levels showed prognostic significance for DFS in a subset of breast cancer patients (ie, patients with > three positive nodes). Patients with greater than three positive lymph nodes and thos e with greater than 100 fmol/ml of plasma c-erbB-2 levels before thera py had significantly shorter DFS than did those patients with 100 fmol /mL or less c-erbB-2 levels. Conclusion: In breast cancer patients, de termination of c-erbB-2 levels before therapy.is an important biomarke r to assess the extent of disease spread in the lymph nodes. Postchemo therapy c-erbB-2 levels are also a prognostic indicator for DFS in pat ients who receive chemotherapy. finally in a subgroup af patients with greater than three positive nodes, prechemotherapy c-erbB-2 levels ar e a prognostic marker for response of patients to standard chemotherap y. (C) 1998 by American Society of Clinical Oncology.