Abstract P1-01-12: Comparison of local clinical subtyping to central molecular classification using microarray-based expression test in breast cancer patients

Background: Measurement of estrogen receptor (ER), progesteron receptor (PR) and human epidermal growth factor receptor 2 (HER2) status in early breast cancer is critical for informing treatment recommendations. Targetprint®, a commercially available microarray-based test, measures mRNA levels of ER, PR and HER2 genes. The aim of this study was to investigate the concordance and accuracy of local clinical subtyping by inmunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) with TargetPrint®. Material and Methods: We collected data retrospectively from 109 early breast cancer patients from 17/5/2012 to 17/4/2015. All of them underwent surgery. ER, PR and HER2 status were assessed by IHC in tumor samples. For HER2 IHC 2+ cases, additional FISH was used. These results were compared with microarray mRNA quantifications. Microarrays were all performed in formalin-fixed paraffin-embedded (FFPE) tumor samples. Accuracy of TargetPrint® was evaluated with positive (PPV) and negative (NPV) predictive value considering IHC as "Gold Standard". Corcondance between techniques was evaluated with percentage of concordance and Cohen9s κ coefficient. The interpretation of k Coefficient is done by correlating its value with a qualitative scale (Landis and Koch, 1977): 0 is considered poor; 0,01-0.20 is slight; 0,21-0,40 is fair; 0,41-0,60 is moderate; 0,61-0,80 is substantial; 0,81-1 is almost perfect. Results: 100% of tumor samples were RE positive for both IHC and TargetPrint®. All 109 patients resulted HER2 IHC negative, 3 of them were HER2 TargetPrint® positive. Regarding RP, 80% of tumor samples were IHC and TargetPrint® positive, 11% IHC and TargetPrint® negative, 5% negative by IHC and positive by TargetPrint® and 4% positive by IHC and negative by TargetPrint®. For ER, concordance was 100%, k=1. For PR, concordance was 90,83%, k=0,65 (95%CI 0,45-0,85). In the case of HER2, percentage of concordance was 97,25%, k=0 (kappa paradox). TargetPrint had PPV 1 and NPV 0 assesing ER. For PR, TargetPrint PPV is 0,93 and NPV is 0,75. For HER2, TargetPrint PPV is 0 and NPV is 0,97. Conclusions: To the best of our knowledge, this is the first study exploring concordance between IHC/FISH and Targetprint® in FFPE tumor samples. According to previous data in fresh tissue, almost perfect concordance for ER and HER2 as well as substantial concordance for PR were seen. We suggest lack of accuracy in IHC technique, in microarray test or intra-tumor heterogeneity as possible reasons for the less consistent accordance in PR. It would be interesting to further design a prospective study to address this question. Citation Format: Fernandez-Abad M, Cortes-Salgado A, Martinez-Janez N, Cortez-Castedo P, Munoz-Del Toro J, Lopez-Miranda E, Guerra-Alia EM, Gion-Cortes M, Reguera-Puertas P, Martinez-Saez O, Molina-Cerrillo J, Villamayor M, Roberts-Cervantes E, Gomez-Rueda A, Carrato-Mena A. Comparison of local clinical subtyping to central molecular classification using microarray-based expression test in breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-01-12.