Prognosis of breast cancer: evidence for interaction between c-erbB-2 overexpression and number of involved axillary lymph nodes

Abstract

The prognostic significance of c-erbB-2 oncogene amplification or overexpression in relation to axillary lymph node metastasis is controversial. We investigated this question in 159 cases of operable breast cancer: 56 patients with node negative disease and 103 patients with pathological involvement of axillary lymph nodes. c-erbB-2 overexpression was assessed by immunohistochemistry using a polyclonal antibody raised 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 considered (P = 0.0124), and also for patients with positive axillary lymph nodes (P = 0.0026). c-erbB-2 overexpression had no influence on survival of node negative patients (P = 0.7972). A multivariate survival analysis using the Cox proportional hazard model revealed that number of involved lymph nodes, c-erbB-2 overexpression, ER status, and tumour size 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 between these two factors was observed (P = 0.0002), suggesting that the expression of prognostic power of c-erbB-2 overactivity is related to the number of involved axillary lymph nodes. The 159 patients were then subdivided into three groups: node negative (-ve) (56); 1-6 node positive ( + ve) (55); and ≥7 node +ve (48). This cutoff criterion gave the most numerically equitable distribution of the 159 patients into three groups. The relative risk of death increased stepwise from 0.86 (95% CI 0.26-2.78) for node negative patients, to 1.95 (95% CJ 0.82-63) for 1-6 node positive patients, to 2.23 (95% Cl 1.15-4.35) for >7 node positive patients. Our results suggest that the prognostic influence of c-erbB-2 overexpression increases arithmatically with increasing number of involved axillary lymph nodes.