c‐erbB‐2 (HER‐2/neu) gene amplification is a better indicator of poor prognosis than protein over‐expression in operable breast‐cancer patients

Our aim was to compare the prognostic value of c‐erbB‐2 gene amplification analyzed by Southern blot with that of protein (p185) over‐expression measured by immunohistochemistry in 172 patients with operable breast cancer (BC). Amplification and p185 over‐expression were found in 31 (18%) and 51 (30%) BCs, respectively. All but 1 of the tumors showed both amplification and over‐expression, while 21 (12%) tumors displayed over‐expression without amplification. The risk of death associated with c‐erbB‐2 gene amplification and p185 over‐expression was evaluated by multivariate analysis, taking into account tumor size, histoprognostic grade, hormone receptors and axillary node status. During a mean follow‐up of 9.5 (±2) years, node involvement (p < 0.001), c‐erbB‐2 gene amplification (p = 0.02) and negative hormone receptors (p = 0.02) were found to be independent prognostic indicators of the risk of death. Over‐expression of p185 with no amplification was not correlated with this risk. When the risk of death associated with c‐erbB‐2 amplification was studied according to chemo‐ and hormone therapy, no significant difference was observed between subgroups of subjects. Amplification was also associated (p = 0.02) with the risk of multifocal distant metastases (i.e., metastases detected concomitantly in at least 2 sites) and, thus, with BC aggressiveness. These data show the importance of c‐erbB‐2 gene amplification in predicting the long‐term outcome of patients and in selecting eligible patients for c‐erbB‐2–targeted therapies. © 2001 Wiley‐Liss, Inc.