ER and PR Immunohistochemistry and HER2 FISH vs. Oncotype DX®: Implications for Breast Cancer Treatment
MiHee M Park, Joshua J Ebel, Debra L Zynger. Ohio State University Medical Center, Columbus, OH
Background: Hormone receptor and human epidermal growth factor (HER2) are potent clinical biomarkers to predict response to adjuvant therapy for breast cancer. Immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH) are validated techniques while reverse-transcriptase polymerase chain reaction (qRT-PCR) is a relatively new assay for this purpose. Our aim is to evaluate ER, PR, and HER2 concordance between IHC and FISH, and a commercially available qRT-PCR-based assay, Oncotype DX® (Genomic Health, Redwood City, CA, USA).
Design: A retrospective review of invasive breast carcinoma resections performed at our institution from 2008 to 2012 was conducted to isolate cases in which an Oncotype DX® assay was utilized. ER and PR by IHC and HER2 by FISH had been previously assessed. Cases were organized by whether biomarkers were performed on: biopsy only, resection only, or biopsy and resection. When biomarkers were performed on both the biopsy and resection, analysis was done on the resection data as this was the same tissue block used for Oncotype DX® testing. For discordant cases in which the biopsy was used, markers were newly performed on the resection block and this data was used for analysis. Statistical methods to calculate correlation and agreement included the Pearson correlation coefficient (r) and Cohen's kappa (κ), respectively.
Results: ER showed a concordance of 98.9% (262/265), r=0.42 (95% confidence interval (CI): 0.31-0.51). Positive percent agreement (PPA) for ER was 98.9% (262/265). Negative percent agreement (NPA) and κ could not be calculated because Oncotype DX® testing was not ordered for IHC ER-negative cases, precluding true negative results. PR was concordant in 91.3% (242/265), r=0.80 (95% CI: 0.75-0.84), and κ=0.63 (95% CI: 0.50-0.77). PPA for PR was 100% (218/218) and NPA was 51.1% (24/47). HER2 results were concordant in 99.2% (245/247), r=0.34 (95% CI: 0.23-0.45), and κ=0.12 (95% CI: -0.08-0.31). PPA for HER2 was 0% (0/2) and NPA was 100% (245/245). Of the 3 FISH HER2-amplified cases, 2 (66.7%) were negative and 1 (33.3%) was equivocal by Oncotype DX®; all FISH HER2-equivocal cases (n=3) were negative by Oncotype DX®.
Conclusions: While our results exhibited high to moderate concordance rates between IHC and Oncotype DX® for ER and PR biomarkers, our data showed poor PPA for HER2. Oncotype DX® may not accurately identify HER2-positive breast carcinomas in comparison to FISH. We recommend exercising caution in the interpretation of discordant results.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 31, Wednesday Morning