The New Hormone Receptor Cutoff: For Defining Hormone Receptor Positivity What Is the Impact of the New 1% Cutoff Versus the Old 10% Cutoff on Hormone Receptor Concordance between Local IHC, Central IHC and Central RT–PCR?
FL Baehner, R Gray, B Childs, T Maddala, M Liu, S Rowley, N Davidson, S Shak, LJ Goldstein, GW Sledge, JA Sparano, S Badve. University of California, San Francisco, San Francisco, CA; Genomic Health, Redwood City, CA; Eastern Cooperative Oncology Group, Indianapolis, IA; Sanofi Aventis, Bridgewater, NJ
Background: Accurate assessment of hormone receptors (HR) in breast carcinoma is important. It is recommended that >1% should be used as the standard cutoff to define HR positivity (CAP 2009). To characterize the effect that this has on the concordance between laboratories and methods, we examined HR concordance between local and central IHC and central RT-PCR using clinical trial breast cancers from E2197.
Design: Tumors from 761 E2197 pts were examined. ER and PR results were obtained by: local IHC (reported by the site), central IHC (1D5 and 636 performed in duplicate on 1.0 mm core TMAs using Allred scores of >2, the traditional cutpoint (corresponding to either 10% of cells staining 1+ or 1% of cells staining 2+) & the new cutoff of ≥2 (1% of cells 1+ positive)); and, by central quantitative RT-PCR analysis using Oncotype DX (RNA extracted from formalin fixed paraffin embedded tissue, pre-defined cutoffs of 6.5 for ER and 5.5 for PR).
Results: Results from local IHC (761 pts) were compared with central IHC (755 pts) and RT-PCR (761 pts). Using a central IHC cutoff of AS>2 the concordance between central and local IHC was 90% for ER, 84% for PR and 90% for HR, while for central IHC and central RT-PCR it was 93% for ER, 90% for PR and 93% for HR. Using a central IHC cutoff of AS≥2 the concordance between central and local IHC was 91% for ER, 84% for PR and 90% for HR while for central RT-PCR it was 94% for ER, 89% for PR and 93% for HR.
Conclusions: The new HR cutpoint had a negligible impact on ER and PR concordance between central and local IHC and between central IHC and central RT-PCR. A standardized cutoff value of 1% may be easier to uniformly apply and concordance studies to examine the impact of this new cutoff are warranted.
|Local IHC vs Central IHC (AS>2)||90 (88, 92)||84 (82, 87)||90 (87, 92)|
|Local IHC vs Central IHC (AS≥2)||91 (88,93)||84 (81,86)||90 (87,92)|
|Local IHC vs RT-PCR||91 (89, 93)||87 (85, 90)||91 (89, 93)|
|Central IHC (AS>2) vs RT-PCR||93 (91, 94)||90 (88, 92)||93 (91, 95)|
|Central IHC (AS≥2) vs RT-PCR||94 (92,95)||89 (87,92)||93 (91,95)|