PROGNOSIS OF BREAST-CANCER - EVIDENCE FOR INTERACTION BETWEEN C-ERBB-2 OVEREXPRESSION AND NUMBER OF INVOLVED AXILLARY LYMPH-NODES

The prognostic significance of c-erbB-2 oncogene amplification or over expression in relation to axillary lymph node metastasis is controvers ial. We investigated this question in 159 cases of operable breast can cer: 56 patients with node negative disease and 103 patients with path ological involvement of axillary lymph nodes. c-erbB-2 overexpression was assessed by immunohistochemistry using a polyclonal antibody raise d against a synthetic peptide fragment of the oncoprotein. The overall incidence of c-erbB-2 overexpression was 35%. c-erbB-2 overexpression was significantly related to survival when all patients were consider ed (P = 0.0124), and also for patients with positive axillary lymph no des (P = 0.0026). c-erbB-2 overexpression had no influence on survival of node negative patients (P = 0.7972). A multivariate survival analy sis using the Cox proportional hazard model revealed that number of in volved lymph nodes, c-erbB-2 overexpression, ER status, and tumour siz e were independently related to prognosis (P = 0.0000, 0.0012, 0.0112, and 0.0204, respectively). When an interaction term was introduced in the Cox model between c-erbB-2 overexpression and number of involved axillary lymph nodes, a statistically highly significant interaction b etween these two factors was observed (P = 0.0002), suggesting that th e expression of prognostic power of c-erbB-2 overactivity is related t o the number of involved axillary lymph nodes. The 159 patients were t hen subdivided into three groups: node negative (-ve) (56); 16 node po sitive (+ve) (55); and greater than or equal to 7 node +ve (48). This cutoff criterion gave the most numerically equitable distribution of t he 159 patients into three groups. The relative risk of death increase d stepwise from 0.86 (95% CI 0.26-2.78) for node negative patients, to 1.95 (95% CI 0.82-4.63) for 1-6 node positive patients, to 2.23 (95% CI 1.15-4.35) for >7 node positive patients. Our results suggest that the prognostic influence of c-erbB-2 overexpression increases arithmat ically with increasing number of involved axillary lymph nodes. (C) 19 95 Wiley-Liss, Inc.