Long-term prognostic significance of HER-2/neu in untreated node-negative breast cancer depends on the method of testing

Overexpression was classified semiquantitatively according to a score (0 to 3+) (HER-2_SCO). FISH was used to analyse HER2/neu amplification (HER-2_AMP). Patients classified 2+ by IHC were examined with FISH for amplification (HER-2_ALG). Patients with 3+ overexpression as well as amplification of HER-2/neu were positive for the combined variable HER2_COM. These variables were compared with tumour size, histological grade and hormone receptor status.HER-2_SCO was 3+ in 20% of all tumours. HER-2_ALG was positive in 22% and amplification (HER-2_AMP) was found in 17% of all tumours. Eleven percent of the tumours showed simultaneous 3+ overexpression and amplification. Only histological grade (relative risk [RR] 3.22, 95% confidence interval [CI] 1.73–5.99, P = 0.0002) and HER-2_AMP (RR 2.47, 95% CI 1.12–5.48, P = 0.026) were significant for disease-free survival in multivariate analysis. For overall survival, both histological grade (RR 3.89, 95% CI 1.77–8.55, P = 0.0007) and HER-2_AMP (RR 3.08, 95% CI 1.24–7.66, P = 0.016) retained their independent significance.The prognostic significance of HER-2/neu in node-negative breast cancer depends on the method of testing: only the amplification of HER-2/neu is an independent prognostic factor for the long-term prognosis of untreated node-negative breast cancer.Human epidermal growth factor receptor-2 is a proto-oncogene that encodes a cell-surface receptor designated HER-2/neu or c-erbB-2. Gene amplification and/or protein overexpression occurs in 14–30% of all breast cancers [1-3]. Initially, the adverse prognostic impact of HER-2/neu in breast cancer was the main focus of research. However, results from different study groups were not entirely consistent. Studies that supported the initially reported adverse prognosis in breast cancer [1,3] were later followed by reports that failed to show any association with prognosis [4,5]. Although no consensus exists concerning the prognostic value of HER-2/neu, an increasing quanti