Comparison of HER2 status by fluorescence in situ hybridization and immunohistochemistry to predict benefit from dose escalation of adjuvant doxorubicin-based therapy in node-positive breast cancer patients.

Document Type


Publication Date



Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Chemotherapy, Adjuvant, Cyclophosphamide, Doxorubicin, Female, Fluorouracil, Gene Amplification, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Lymphatic Metastasis, Polymerase Chain Reaction, Prognosis, Randomized Controlled Trials as Topic, Receptor, erbB-2, Survival Analysis, Treatment Outcome, Tumor Markers, Biological


American Society of Clinical Oncology





First Page


Last Page




JAX Source

J Clin Oncol 2005 Jul 1; 23(19):4287-97.




PURPOSE: HER2 is a clinically important tumor marker in breast cancer; however, there is controversy regarding which method reliably measures HER2 status. We compared three HER2 laboratory methods: immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR), to predict disease-free survival (DFS) and overall survival (OS) after adjuvant doxorubicin-based therapy in node-positive breast cancer patients.

METHODS: This is a Cancer and Leukemia Group B (CALGB) study, using 524 tumor blocks collected from breast cancer patients registered to clinical trial CALGB 8541. IHC employed CB11 and AO-11-854 monoclonal antibodies; FISH used PathVysion HER2 DNA Probe kit; PCR utilized differential PCR (D-PCR) methodology.

RESULTS: Cases HER2 positive by IHC, FISH and D-PCR were 24%, 17%, and 18%, respectively. FISH and IHC were clearly related (kappa = 64.8%). All three methods demonstrated a similar relationship for DFS and OS. By any method, for patients with HER2-negative tumors, there was little or no effect of dose of adjuvant doxorubicin-based therapy. For patients with HER2-positive tumors, all three methods predicted a benefit from dose-intense (high-dose) compared with low- or moderate-dose adjuvant doxorubicin-based therapy.

CONCLUSION: FISH is a reliable method to predict clinical outcome following adjuvant doxorubicin-based therapy for stage II breast cancer patients. There is a moderate level of concordance among the three methods (IHC, FISH, PCR). None of the methods is clearly superior. Although IHC-positive/FISH-positive tumors yielded the greatest interaction with dose of therapy in predicting outcome, no combination of assays tested was statistically superior.

J Clin Oncol 2005 Jul 1; 23(19):4287-97.

Please contact the Joan Staats Library for information regarding this document.