Local versus central HER2 immunohistochemistry correlates with kinetic RT-PCR but only central immunohistochemistry and RT-PCR predict pathological complete response: results from the neoadjuvant multicenter GeparTrio trial.
Authors: S Loibl, B Müller, M Roller, R Kronenwett, S Darb-Esfahani, M Komor, C von Toerne, R Wirtz, G von Minckwitz, C Denkert
Journal: Cancer Research (2009)

Abstract Abstract #1070 Background: There are several methods for determination of HER2 overexpression. Immunohistochemistry (IHC) has been set up as the gold standard in routine diagnostics to identify patients eligible for anti-HER2 therapy. Nonetheless, there is still controversy about the predictive value of HER2 overexpression and pathological response to neoadjuvant anthracycline/taxane-based chemotherapy.&amp;#x2028; Methods: In this study, we investigated the HER2 expression levels in formalin-fixed, paraffin-embedded pre-treatment punch biopsies by kinetic one-step RT-PCR (kRT-PCR); local IHC performed at the pathological institutes of the participating centers; and centrally performed IHC in 150 patients from the neoadjuvant GeparTrio study (NCT00544765), where patients were treated with docetaxel, doxorubicin and cyclophosphamide (TAC) but received no trastuzumab therapy regardless of the individual HER2 status. HER2 was considered positive for IHC if expression was 3+ and for mRNA expression if normalized level was &amp;gt;/= 18.0 arbitrary units (as defined by bimodal expression for this cohort). We evaluated the associations by Spearman's rho correlation between the different methods as well as the best method that might predict a pathological complete response to this neoadjuvant chemotherapy.&amp;#x2028; Results: A randomly selected subset out of 150 of 2,090 patients was included in this analysis. This is a representative collective of TAC-treated patients from the GeparTrio trial with a pCR rate (ypT0; ypTis/ypN0) of 23%. The different methods revealed a HER2 positivity of 31% for the local analyses, 16% for the central HER2 testing and 20% positivity for kRT-PCR analyses for this study collective, compared to 28% for the entire trial population. Local determination of HER2 showed a correlation with central laboratory (RS=.418, P&amp;lt;.001, N=106) and kRT-PCR results (RS=.428, P&amp;lt;.001, N=120), and centrally assessed HER2 expression correlated with the results of kRT-PCR (RS=.923, P&amp;lt;.001, N=115). Binary logistic regression with the locally determined HER2 expression revealed no significant results in prediction of a pathological complete response (P=.802, N=121), whereas the results from central IHC (P=.038, OR 2.84, N=119) as well as the results from kRT-PCR (P=.047, OR 2.47, N=134) were significant.&amp;#x2028; Conclusions: The value of HER2 expression and response to neoadjuvant chemotherapy is still controversial. Our results on this subset of patients show that kRT-PCR of HER2 mRNA expression and centrally performed IHC but not local HER2 assessment predicts pCR for neoadjuvant TAC chemotherapy. Theses results need further confirmation on a larger group of patients. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1070.