P1-07-06: High Concordance of Protein (by IHC), Gene (by FISH; HER-2 Only) and Microarray Readout (by TargetPrint) of ER/PR/HER2: Results from the MINDACT Trial.
Authors: Viale G , Bogaerts J , van't Veer L , Rutgers E , Piccart M , de Snoo F , Engelen K , Russo L , Dell'Orto P , Glas A , Cardoso F ,   On Behalf of the TRANSBIG Consortium & the MINDACT Investigators
Published: June 2012

Abstract
Background
Previously, the micro-array readout of ER, PR and HER2 by TargetPrint was shown to be strongly correlated with high quality immunohistochemistry (IHC)/FISH assessment, especially for ER and HER2. Concordance rates were 93% (k=0.79) for ER; 83% (k=0.65) for PR and 96% for HER2 (k=0.88) in 636 patients (Roepman et al., Clin Cancer Res, 2009).
This study analysis was undertaken to further determine the correlation of microarray readout with IHC/FISH assessment both locally and centrally determined in the 1st 800 pts enrolled in the MINDACT trial. This work is essential to determine the quality of biological data in the two risk assessment methods used in MINDACT based upon which adjuvant chemotherapy decision is made, in order to exclude bias.
Methods: ER/PR/HER2 IHC assessment was performed on the 1st 800 primary breast cancers (BC) of pts enrolled in the MINDACT study. The assessment was performed locally at each center (n=800) and by central review at the laboratory of the European Institute of Oncology (n=626). A tumor was classified positive for ER and PR when 1% of tumor cells showed positive staining. HER2 IHC status was scored as 0, 1+, 2+ or 3+; a score of 3+ was considered positive. In 2+ cases FISH was performed to assess final HER2 status. Gene expression data for ER, PR and HER2 were obtained by TargetPrint stratified as receptor positive or negative using previously determined and validated thresholds for ER, PR and HER2 mRNA levels (n=800).
Results: Comparison of local assessment (IHC & FISH for HER2) with central review indicated highly similar results for receptor readout with a concordance of 98% (k=0.90) for ER; and 96% for HER2 (k=0.80) and slightly lower for PR (90% (k=0.72)).
Comparison of central assessment (IHC & FISH for HER2) with micro array readout by TargetPrint indicated highly similar results for receptor readout with a concordance of 97% (k=0.88) for ER and 95% for HER2 (k=0.76). For PR the concordance was lower but still quite acceptable (85% (k=0.62)).
Conclusion: Local and centrally assessed ER, PR and HER2 status in the first 800 MINDACT patient samples indicate a high level of quality for pathology in the local participating hospitals. These results exclude any bias induced by a lower quality of “traditional” pathology results as compared to the centrally assessed MammaPrint, both used for risk assessment and adjuvant chemotherapy decision in the MINDACT trial. The microarray-based assessment of ER, PR and HER2 gives results comparable to IHC & FISH and provides an objective and quantitative assessment of tumor receptor status. These results indicate that TargetPrint can serve as a second pathology assessment for locally assessed parameters, especially since TargetPrint is part of a multi-profile platform for breast cancer treatment management. This work was funded by the Breast Cancer Research Foundation and the EU Framework Program VI.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-07-06.