Publication Year: 2000 Visited: 111

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HER-2 as a Predictive Marker in Node-Positive (N+) Breast Cancer (BC) Patients (Pts) Randomly Treated with CMF or an Anthracycline-Based Regimen. Angelo Di Leo, Denis Larsimont, David Gancberg, Tero Järvinen, Marc Beauduin, Stella Dolci, Marianne Paesmans, Jean-Pierre Lobelle, Jorma Isola, Martine J. Piccart, Jules Bordet Institute, Brussels, Belgium; Tampere Univ Hosp, Tampere, Finland; Jolimont-Lobbes Hosp, Haine St Paul, Belgium; Pharmacia-Upjohn, Brussels, Belgium.

Last year we presented the 4-yr results of a randomised trial comparing two epirubicin-cyclophosphamide regimens (HEC: full dose; EC: low dose-intensity) with classical CMF, in 777 N+ BC pts (Proc ASCO 18:69a, 1999). Archival samples of the primary tumor were collected for 481 of these pts to assess the predictive value of HER-2. HER-2 was evaluated by immunohistochemistry (IHC) in one laboratory (lab2), using different antibodies (Abs). Below we report the results of the event-free survival (EFS) comparison between HEC and CMF{table}These results suggest that the predictive value of HER-2 may vary according to the Abs selected for IHC evaluation. We have also explored the reproducibility of HER-2 evaluation by IHC. 321 of the original 481 samples were independently evaluated in two different laboratories (lab1 and lab2) using the same Ab (CB-11) and cut-off. While 250 cases were HER-2 negative in both labs, 32 (45 %) of the 71 lab1 positive cases were HER-2 negative in lab2. The discordance observed between the two labs may result from the antigen retrieval procedures. These data suggest that the evaluation of HER-2 by IHC needs to be standardised. We are now evaluating HER-2 by fluorescence in situ hybridization (FISH). We are also examining topo-isomerase II alpha (topo IIa) gene amplification and deletion by FISH. In vitro data from our group (Jarvinen et al, Am J Pathol, in press) suggest that HER-2 and topo IIa amplified tumors are sensitive to anthracyclines, while HER-2 amplified/topo IIa deleted tumors are resistant. Results of the FISH analysis will be available for the meeting.