erbB-2 (HER-2) and breast cancer progression

The purpose of this study was to explore differences in erbB-2 alterations in recurrent or metastatic disease, as compared with the primary tumor. Primary invasive breast cancers and subsequent local, regional, or distant metastases from 113 patients were examined. Primary and all metastatic or recurrent tumors were evaluated for erbB-2 expression using immunohistochemistry (with CB11, TAB 250, DAKO anti-erbB-2, HercepTest) and fluorescence in situ hybridization. Immunohistochemical data derived from the 4 reagents on the same tumor sample were highly correlated (pair-wise correlation range, 78-90%). Immunohistochemical and fluorescence in situ hybridization erbB-2 data were also generally concordant (average agreement, 82%; range, 75-87%). Approximately 80% of the primary and recurrent or metastatic tissues from the same patient had similar patterns of erbB-2 protein expression and gene copy number, although in approximately 20%, disagreement was observed. Discordant cases were mostly erbB-2 normal primary tumors with altered metastases, although the opposite pattern was also observed. Interestingly, erbB-2 discordance, based on CB11 data, was associated with subsequent survival, whereas there were no similar associations with other erbB-2 stains. In approximately 80% of patients, erbB-2 protein expression and gene copy number were similar in the primary tumor and locally recurrent or distant metastases. The lack of complete concordance suggests clonal selection or genetic drift in some cases.