P1-07-22: A Venezuelan Study of Breast Cancer Estrogen Receptor, Progesterone Receptor and HER2 Receptor Expression by the Standard Method, Immunohistochemistry (IHC), Compared to a New Method, Quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR).

Abstract

Abstract Background: Assessment of ER, PR and HER2 is of significant importance in breast cancer diagnosis and treatment. We have performed the first large assessment of central IHC for ER, PR and HER2 by a South American (Caracas, Venezuela) Central Lab to Central Lab RT-PCR by Oncotype DX®. Design: Breast cancer specimens from the Fundación BADAN were evaluated by IHC for ER (clone 1D5), PR (clone 636) using 1% staining for positivity using ASCO/CAP guidelines and HER2 (clone A0485) using ASCO/CAP guidelines of 3+ in ≥30%. Standardized quantitative RT-PCR analysis for ER and PR used Oncotype DX with the pre-defined cutoffs of 6.5 units and 5.5 units for positivity, respectively. For HER2 the standard pre-defined cutoffs were used: positive ≥11.5 units, equivocal >10.7-<11.5 units, and negative ≥10.7 units. For HER2 concordance analysis the equivocal range was excluded from both assays according to ASCO/CAP Guidelines (Wolff et al, 2006). For all quantitative RT-PCR assessments the reference normalized expression measurements ranged from 0 to 15, where each 1-unit increase reflects about a 2-fold increase in RNA. Result: Evaluable data was obtained in 96 pts for ER, 95 pts for PR (1 patient assessment unavailable) and 89 pts for HER2 (7 patient assessments unavailable). Two-by-two tables (below) compare IHC versus RT-PCR for ER, PR and HER2. The overall concordance for ER between IHC and RT-PCR was 94% (Kappa 0.467; 95% CI 0.107, 0.828); for PR between IHC and RT-PCR was 92% (Kappa 0.668; 95% CI 0.457, 0.878); and for HER2 between IHC and RT-PCR was 97% (Kappa = 0.649; 95% CI 0.280, 1.000). Three IHC 2+ cases and 4 equivocal cases by Oncotype DX were excluded from Concordance and Kappa statistics. Conclusion: RT-PCR by Oncotype DX for ER, PR and HER2 status is useful for active monitoring of IHC assays as mandated by ASCO/CAP guidelines. There is a high degree of overall concordance between central IHC performed in South America (Caracas, Venezuela) and central RT-PCR for ER, PR and HER2 status. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-07-22.