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- W2589242534 abstract "611 Background: Common practice for comparing different technologies measuring the same biomarker is to establish cut-offs using Receiver Operator Characteristic (ROC) curves and maximizing sensitivity/specificity. We introduce a new method for establishing RT-qPCR cut-points using gene expression across biologic subtypes and compare to standard methods. Methods: A RT-qPCR training set was established to identify biologic subtypes of breast cancer using the PAM50 gene expression signature. 155 invasive breast cancers and 16 normal breast samples, procured in formalin-fixed paraffin-embedded tissue blocks, were used to identify prototypic samples for the common biologic subtypes (Luminal A, Luminal B, HER2-enriched, Basal-like, and Normal). Cut-points for ESR1, PGR, and ERBB2 were determined based on their expression across the training set subtypes and used to determine sensitivity/specificity in an independent test set of 793 invasive breast cancers from the GEICAM 9906 study (randomized phase III trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by paclitaxel for early breast cancer). Fixed cut-points (low vs intermediate/high) were applied to the continuous RT-qPCR data and compared to IHC scores tested for in a central facility. Results: There was good agreement between RT-qPCR gene expression and immunohistochemistry scoring for clinical markers ESR1/er, PGR/pr, and ERBB2/her2. The accuracy was significantly lower for MKI67/ki67, EGFR/egfr, and KRT5/ck5/6 (Table). Discrepancies between the Herceptest and CISH for 2+ and 3+ samples showed that RT-qPCR agreed better with the Herceptest (AUC: 0.95 vs 0.93). Conclusions: Calling cut-points based on RT-qPCR expression across subtypes is reproducible across datasets and has good agreement with expression by immunohistochemistry for clinically used biomarkers. Agreement between gene and protein expression for common biomarkers in breast cancer. Accuracy Area under curve (AUC) Sensitivity (%) Specificity (%) Gene/protein expression ESR1/er 0.89 96 72 PGR/pr 0.90 83 86 ERBB2/her2 0.95 92 87 ki67/MKI67 0.74 71 62 EGFR/egfr 0.82 80 71 KRT5/ck5/6 0.61 61 53" @default.
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- W2589242534 date "2011-05-20" @default.
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- W2589242534 title "Determining agreement between immunohistochemistry and RT-qPCR for standard biomarkers in breast cancer: Validation on GEICAM 9906 clinical trial." @default.
- W2589242534 doi "https://doi.org/10.1200/jco.2011.29.15_suppl.611" @default.
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