[267] 100% Concordance between IHC and FISH HER2 Testing Cannot Be Achieved Using N9831 Cohort

AE McCullough, B Chen, DW Hillman, KS Tenner, RB Jenkins, MM Reinholz, WL Lingle, AC Dueck, EA Perez. Mayo Clinic, Scottsdale AZ, Rochester MN, Jacksonville FL

Background: Accuracy of HER2 testing is critical for selecting patients eligible for targeted anti-HER2 therapy. One aspect of the 2007 CAP/ASCO guideline recommendations for HER2 testing is to standardize HER2 interpretation.
Design: We analyzed HER2 IHC and FISH results in patients enrolled in NCCTG N9831 trial using the interpretation guidelines provided by the testing manufacturers (Dako HercepTest for IHC and Abbott/Vysis PathVysion for FISH) and the 2007 CAP/ASCO guidelines.
Results: A total of 2809 cases with both IHC and FISH HER2 results are included in this analysis. 2467 cases (88%) are IHC 3+ using HercepTest criteria of >10% 3+ staining; 2577 cases (92%) are HER2 amplified using PathVysion criteria of HER2:CEP17 ratio >=2.0. Using the 2007 CAP/ASCO interpretation guidelines, 2367 cases (84%) are HER2 IHC 3+, and 2539 cases (90%) are HER2 amplified. 252 cases (9.0%) are HER2 amplified but showed no or equivocal overexpression. 80 cases (2.8%) showed HER2 overexpression without amplification. 49 cases (1.7%) are HER2 IHC 0 or 1+, but showed HER2 amplification. A concordance of 99% is achieved between IHC and FISH when tumors show 100% of 3+ staining by IHC. The detailed data on concordance between both methods are presented in the table.

Concordance of IHC and FISH (N=2809)
IHCFISH >=2.0FISH >2.2
3+> 10%2377/2467 (96.4%)2365/2467 (95.9%)
3+>20%2325/2403 (96.8%)2317/2403 (96.4%)
3+>30%2293/2367 (96.9%)2287/2367 (96.6%)
3+>40%2205/2252(97.9%)2202/2252 (97.8%)
3+>50%2142/2180(98.3%)2141/2180 (98.2%)
3+>60%2092/2124 (98.5%)2091/2124 (98.4%)
3+>70%1987/2012 (98.8%)1986/2012 (98.7%)
3+>80%1827/1845 (99.0%)1826/1845 (98.9%)
3+>90%1707/1723(99.1%)1706/1723 (99.0%)
3+=100%1706/1722 (99.1%)1705/1722 (99.0%)

Conclusions: No IHC 3+ percentage predicted 100% FISH amplification. Testing with either one of the methods would exclude small numbers of patients from potential benefits of anti-HER2 therapy. These data do not suggest superiority of either IHC or FISH for determining HER2 status. Clinical outcome data will be discussed. We gratefully acknowledge support from the Breast Cancer Research Foundation, Genentech, and NIH CA25224 for this study.
Category: Breast

Tuesday, March 23, 2010 1:00 PM

Poster Session IV # 1, Tuesday Afternoon


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