Change of HER-2/neu status in a subset of distant metastases from breast carcinomas

It is assumed that HER-2/neu status remains consistent in breast carcinoma during metastatic spread, but in most previous studies primary tumours were compared with concurrent regional lymph node metastases. The present study investigated 31 breast carcinomas and their corresponding lymph node and distant metastases for HER-2/neu status by immunohistochemistry (HercepTest) and fluorescence in situ hybridization (FISH) (PathVysion). In 14 cases, serum HER-2/neu (SHER-2) was measured sequentially using the Bayer Immuno 1 HER-2/neu assay. Comparing HER-2/neu immunohistochemistry of primary tumours and distant metastases case by case, increased HER-2/neu expression was found in the distant metastases in 15 cases (48.4%), three (9.7%) of which showed an increase from score 0 to score 3+. In contrast, lymph node metastases showed the same HER-2/neu expression as the primary tumours, confirmed by FISH. Two cases, which showed HER-2/neu score 3+ and HER-2/neu amplification in the primary tumours, revealed increased SHER-2 levels above 50 ng/ml at the first measurement. Five of the 14 cases (36%) showed an increase of SHER-2 above 50 ng/ml towards the end of the patients' life. On the basis of these results, there is evidence that in a subset of breast carcinomas, HER-2/neu amplification and overexpression occur de novo in distant metastases at a late disease stage.