Abstract P2-05-06: Quantitative measurement of HER2 expression in breast cancers: comparison with “real world” HER2 testing in a multi-center Collaborative Biomarker Study (CBS) and correlation with clinicopathological features
Authors: Yardley DA , Kaufman PA , Adams JW , Krekow L , Savin M , Lawler WE , Zrada S , Starr A , Einhorn H , Schwartzberg LS , Huang W , Weidler J , Lie Y , Paquet A , Haddad M , Anderson S , Brigino M , Bosserman L 
Published: August 2014

Abstract
Background: Accurate determination of HER2 status is critical in determining appropriate therapy for breast cancer patients. The HERmark® assay is a novel method to quantitatively measure HER2 total protein expression (H2T) in breast cancer. In this study, we compared HERmark H2T with central laboratory HER2 retesting and local (site reported) HER2 testing of formalin-fixed, paraffin-embedded (FFPE) breast cancer tissues. The quantitative total HER2 measurements (H2T) by HERmark and results of local HER2 tests were correlated with tumor pathohistological characteristics and overall survival of breast cancer patients.
Methods: 232 FFPE breast cancer tissues were provided by 11 CBS study sites for HER2 testing by the HERmark assay and central laboratory IHC re-testing performed in blinded fashion. Local HER2 immunohistochemistry and/or fluorescence in situ hybridization (FISH) results and valid HERmark H2T and central HER2 IHC results were obtained in 192 cases for analysis.
Results: H2T showed a significant correlation with central HER2 IHC staining intensity (P &lt; 0.0001). The concordance rates of positive and negative HERmark status (excluding equivocal) with those of local HER2 status determined by the CBS sites, and with those of central HER2 IHC status were 84% (Kappa = 0.68) and 96% (Kappa = 0.91), respectively. Higher H2T levels significantly correlated with higher tumor grade (p = 0.007) and negative ER/PR status (p = 0.002). Twenty-six (14%) cases showed discordant (conversion of negative and positive) results between local HER2 status and HERmark status. Of the discordant cases, HERmark significantly agreed with H-score of central HER2 IHC retesting (p = 0.014), as compared with local HER2 status. The concordant negative group (local HER2 negative/H2T low) demonstrated better overall survival (OS) (HR = 0.198, p = 0.0001), compared to that of concordant positive group (local HER2 positive/H2T high). The concordant negative group also showed better OS than that of discordant local HER2 negative/H2T high group (HR = 0.065, p = 0.0003), but showed no significant difference in OS as compared to that of discordant local HER2 positive/H2T low group (HR = 1.774, p = 0.499).). In 24 cases (13%) considered to be “triple negative” by local HER2, ER and PR testing, HERmark re-classified 4 cases (17%) as HER2 positive.
Conclusions: H2T by HERmark yields a continuum of quantitative HER2 protein measurements that shows an excellent correlation with central HER2 IHC retesting and confirms the known correlations between HER2 expression with tumor grade and ER/PR status. OS results of concordant HER2 positive or negative groups (between local HER2 testing and HERmark H2T) confirmed that HER2 positive patients (excluding adjuvant trastuzumab therapy) have worse OS than patients with HER2 negative disease. However, in the HERmark and local HER2 discordant groups, OS appeared to track better with H2T by HERmark and not with the local HER2 status. Novel quantitative HER2 measurements may identify patients with false (+) and (−) HER2 status by local HER2 testing and may provide added clinical value to routine “real world” HER2 testing.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-06.