PURPOSE: To evaluate concordance between local and central laboratory HER2 
testing results in patients from the North Central Cancer Treatment Group 
(NCCTG) N9831 adjuvant trial of trastuzumab.
PATIENTS AND METHODS: NCCTG N9831 is a randomized, phase III clinical trial 
comparing three drug regimens: doxorubicin/cyclophosphamide followed by 
paclitaxel with trastuzumab added concurrently, sequentially, or not at all as 
adjuvant therapy for women with HER2-positive resected breast cancer. 
Originally, patients were eligible if their tumors were HER2 positive by either 
local laboratory immunohistochemistry (IHC) or fluorescence in situ 
hybridization (FISH). A protocol modification in 2002 made central laboratory 
testing mandatory, with additional testing of discordant cases conducted by a 
reference laboratory. Concordance between local and central laboratory, and 
level of agreement between central and reference laboratory HER2 findings in 
discordant cases were examined.
RESULTS: HER2 positivity was confirmed in 85.8% of 2,535 patients registered 
since March 2002. When local and central evaluation used the same methodology, 
concordance was 88.1% for FISH and 81.6% for a diagnostic test for presence of 
the HER2 protein. Among discordant cases examined at the reference laboratory, 
there was 94.3% agreement for IHC (0, 1+, 2+) and 95.2% agreement for FISH (not 
gene amplified).
CONCLUSION: There was a high degree of discordance between local and central 
testing for IHC and FISH, but a high degree of agreement between central and 
reference laboratories. These findings support the importance of using 
high-volume, experienced laboratories for HER2 testing to improve the process of 
selecting patients likely to benefit from trastuzumab therapy.