P5-11-09: High Concordance for Microarray Based Determination of ER, PR and HER2 Receptor Status and Local IHC/FISH Assessment Worldwide in 749 Patients.

Abstract

Abstract Background The level of estrogen receptor (ER), progesterone receptor (PR) and HER2 expression is predictive for prognosis and/or treatment response in breast cancer patients. However, differences in fixation and IHC and subjective interpretation can substantially affect the accuracy and reproducibility of the results. The commercially available TargetPrint test measures the mRNA expression level of ER, PR and HER2 and provides high quality second opinion for local IHC/FISH assessment. This study compares results from the microarray-based TargetPrint with IHC and FISH (for HER2 IHC2+) generated by local standard procedures. Methods Prospective tumor samples were collected for 749 patients diagnosed with breast cancer stage I to IV between February 2008 and January 2011. The mRNA level of ER, PR and HER2 (TargetPrint) was assessed in the Agendia laboratories (Agendia Inc, Irvine, CA; Agendia BV, Amsterdam, the Netherlands) in fresh tumor samples submitted from 22 hospitals from Europe, New Zealand, Japan and US. The results of the IHC/FISH assessments performed according to the local standards at the hospitals were compared to the quantitative gene expression readouts. Results Of the 749 samples, IHC assessment was unknown for 5 ER samples and 4 PR samples; FISH was unknown for 24 samples. TargetPrint read out was not assessed for HER2 for 11 samples. Median age of these patients was 61 years. Comparison of IHC and gene expression read out by TargetPrint showed a concordance of 95% for ER; 82% for PR and 91% for HER2. In this study, only 4% of all IHC ER positive samples were classified negative by microarray. In contrast, 14% of IHC ER negative samples were classified positive by microarray. However for HER2, 28% of IHC/FISH HER2 positive samples were classified negative by microarray and 5% of IHC/FISH HER2 negative samples were classified positive by microarray. Samples with discordant classifications for TargetPrint and local assessment are being reviewed in greater detail by a central pathologist. Conclusions Microarray based readout of ER, PR and HER2 status using TargetPrint is highly comparable to local IHC and FISH analysis in 749 analyzed samples in various hospitals worldwide. The results indicate mRNA expression read out for ER, PR and HER2 by TargetPrint provides high quality second opinion for local IHC/FISH assessment. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-11-09.