Abstract P1-02-02: Concordance of microarray based determination of ER, PR and HER2 receptor status and local IHC/FISH assessment in the prospective neo-adjuvant breast registry symphony trial (NBRST)

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. Previously TargetPrint was shown to be strongly correlated with high quality IHC/FISH assessment, especially for ER and HER2. Concordance rates were 98% (k = 0.90) for ER; 85% (k = 0.62) for PR and 96% for HER2 (k = 0.78) in 619 patients (Viale et al., SABCS 2011). This study compares results from the microarray-based TargetPrint with IHC and FISH conducted according to local standard procedures in the prospective NBRST study. Methods The NBRST study includes women aged 18–90 with histologically proven breast cancer, who are scheduled to start neo-adjuvant chemotherapy (CT) or neo-adjuvant endocrine therapy (ET), and who provide written informed consent. The mRNA level of ER, PR and HER2 (TargetPrint) was assessed at the Agendia laboratory (Agendia Inc, Irvine, CA) in fresh and formalin fixed paraffin embedded tumor samples submitted from 40 institutes in the US. The results of the IHC/FISH assessments conducted according to local standard procedures were compared to the quantitative gene expression readouts. Results There were 355 eligible patients enrolled. 67% of patients are IHC ER positive and 25% Her2 IHC/FISH positive. 11 patients were IHC/FISH HER2 equivocal (all TargetPrint HER2 negative). Comparison of IHC and gene expression read out by TargetPrint showed a concordance of 88% (k = 0.75)for ER; 83% (k = 0.66) for PR and 89% (k = 0.70) for HER2. The discordance range for institutes who submitted more than 10 samples was 0-30% for ER, 0-47% for PR and 0-28% for HER2. 16% of all IHC ER+ samples were classified negative by microarray. In contrast, 4% of IHC ER- samples were classified positive by microarray. However for HER2, as many as 33% of IHC/FISH HER2+ samples were classified negative by microarray; 3% of IHC/FISH HER2- samples were classified positive by microarray. Conclusions Microarray based readout of ER, PR and HER2 status using TargetPrint is comparable to local IHC and FISH analysis in 355 analyzed samples from 40 US institutes but the discordance range for individual institutes was up to 30% for ER and 28% for Her2. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-02-02.