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HER2 Testing by Local, Central, and Reference Laboratories in Specimens From the North Central Cancer Treatment Group N9831 Intergroup Adjuvant Trial

Edith A. Perez, Vera J. Suman, Nancy E. Davidson, Silvana Martino, Peter A. Kaufman, Wilma L. Lingle, Patrick J. Flynn, James N. Ingle, Daniel Visscher, Robert B. Jenkins

From the Mayo Clinic, Jacksonville, FL; Mayo Clinic, Rochester, MN; Sidney Kimmel Cancer Center at Johns Hopkins, Baltimore, MD; John Wayne Cancer Institute, Santa Monica, CA; Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon, NH; and the Metro Minnesota Clinical Community Oncology Program, St Louis Park, MN

Address reprint requests to Edith A. Perez, MD, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224; e-mail: perez.edith{at}mayo.edu

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.

Presented in part at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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