P1-07-12: Assessment of Real World HER2 Status by Immunohistochemistry (IHC) and Fluorescence In Situ Hybridization (FISH) in Breast Cancers: Comparison with HERmark®, a Validated Quantitative Measure of HER2 Protein Expression.

Abstract Background: Accurate assessment of the HER2 status is critical in determining appropriate therapy for patients with invasive breast cancer. ASCO/CAP HER2 testing guidelines caution that up to 20% of routine HER2 testing by IHC/FISH may be unreliable (Wolff et al. JCO 2007;25:118). The HERmark assay is a novel quantitative HER2 protein measurement for determining HER2 status in breast cancer. Central HER2 testing showed high concordance (96-98%) with HERmark for positive and negative categories when equivocal subsets were excluded (Huang et al. Am J Clin Pathol 2010;134:303; Joensuu et al, 2008 SABCS, abstract 2071). In this study, we examined concordance between HERmark and routine HER2 testing by IHC and FISH from “real world” formalin-fixed, paraffin-embedded (FFPE) breast cancers submitted commercially for HERmark testing. Methods: 717 HERmark results on FFPE breast cancers tested from 2008 to 2010 and corresponding HER2 IHC/FISH results were reviewed. The IHC and FISH results, per pathology reports submitted at the time of HERmark testing, were compared to HERmark categorical (negative, equivocal, positive) results. Results: 590 (419) samples had IHC (FISH) and HERmark results available. Of these cases, 92% (94%) were either negative or equivocal by IHC (FISH). The HERmark testing reported 33% HERmark negative, 33% HERmark equivocal and 34% HERmark positive. Comparisons of HER2 status by IHC and FISH vs. HERmark are detailed in Table 1. 19% of cases classified as IHC 0 or 1+ were positive by HERmark; 35% classified as FISH negative were HERmark positive. Of the 158 triple negative cases by IHC/FISH (ER, PR and HER2 negative, data not shown), 38 (24%) were reclassified as HER2 positive by HERmark. Conclusions: Higher than expected discordance between HER2 IHC/FISH and the HERmark assay was observed in this study compared with central HER2 testing of prior study cohorts. Selection bias may have impacted these results as ≥ 92% of cases submitted for HERmark testing were either equivocal or negative by routine HER2 IHC/FISH. Central HER2 FISH retesting of these samples will be performed and compared with HERmark results to further evaluate the discordance observed in this analysis. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-07-12.