PMID- 15994142 OWN - NLM STAT- MEDLINE DCOM- 20050726 LR - 20220321 IS - 0732-183X (Print) IS - 0732-183X (Linking) VI - 23 IP - 19 DP - 2005 Jul 1 TI - 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. PG - 4287-97 AB - 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. FAU - Dressler, Lynn G AU - Dressler LG AD - Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, CB 7295, Mason Farm Rd, Chapel Hill, NC 27599-7295, USA. dressler@med.unc.edu FAU - Berry, Donald A AU - Berry DA FAU - Broadwater, Gloria AU - Broadwater G FAU - Cowan, David AU - Cowan D FAU - Cox, Kelly AU - Cox K FAU - Griffin, Stephanie AU - Griffin S FAU - Miller, Ashley AU - Miller A FAU - Tse, Jessica AU - Tse J FAU - Novotny, Debra AU - Novotny D FAU - Persons, Diane L AU - Persons DL FAU - Barcos, Maurice AU - Barcos M FAU - Henderson, I Craig AU - Henderson IC FAU - Liu, Edison T AU - Liu ET FAU - Thor, Ann AU - Thor A FAU - Budman, Dan AU - Budman D FAU - Muss, Hy AU - Muss H FAU - Norton, Larry AU - Norton L FAU - Hayes, Daniel F AU - Hayes DF LA - eng GR - CA02599/CA/NCI NIH HHS/United States GR - CA03927/CA/NCI NIH HHS/United States GR - CA04326/CA/NCI NIH HHS/United States GR - CA04457/CA/NCI NIH HHS/United States GR - CA07968/CA/NCI NIH HHS/United States GR - CA08025/CA/NCI NIH HHS/United States GR - CA11789/CA/NCI NIH HHS/United States GR - CA12046/CA/NCI NIH HHS/United States GR - CA12449/CA/NCI NIH HHS/United States GR - CA21060/CA/NCI NIH HHS/United States GR - CA25119/CA/NCI NIH HHS/United States GR - CA26806/CA/NCI NIH HHS/United States GR - CA31809/CA/NCI NIH HHS/United States GR - CA31946/CA/NCI NIH HHS/United States GR - CA31983/CA/NCI NIH HHS/United States GR - CA32291/CA/NCI NIH HHS/United States GR - CA33601/CA/NCI NIH HHS/United States GR - CA35279/CA/NCI NIH HHS/United States GR - CA35406/CA/NCI NIH HHS/United States GR - CA35421/CA/NCI NIH HHS/United States GR - CA37135/CA/NCI NIH HHS/United States GR - CA37447/CA/NCI NIH HHS/United States GR - CA41287/CA/NCI NIH HHS/United States GR - CA45374/CA/NCI NIH HHS/United States GR - CA45389/CA/NCI NIH HHS/United States GR - CA45418/CA/NCI NIH HHS/United States GR - CA45564/CA/NCI NIH HHS/United States GR - CA45808/CA/NCI NIH HHS/United States GR - CA47545/CA/NCI NIH HHS/United States GR - CA47555/CA/NCI NIH HHS/United States GR - CA47559/CA/NCI NIH HHS/United States GR - CA47577/CA/NCI NIH HHS/United States GR - CA47642/CA/NCI NIH HHS/United States GR - CA54697/CA/NCI NIH HHS/United States GR - CA77440/CA/NCI NIH HHS/United States GR - CA77651/CA/NCI NIH HHS/United States GR - NCI-U01-CA64061-05/CI/NCPDCID CDC HHS/United States PT - Comparative Study PT - Evaluation Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - 0 (Biomarkers, Tumor) RN - 80168379AG (Doxorubicin) RN - 8N3DW7272P (Cyclophosphamide) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - U3P01618RT (Fluorouracil) RN - CAF protocol SB - IM MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - Biomarkers, Tumor/metabolism MH - Breast Neoplasms/metabolism/pathology/*therapy MH - Chemotherapy, Adjuvant/methods MH - Cyclophosphamide/therapeutic use MH - Doxorubicin/*administration & dosage/therapeutic use MH - Female MH - Fluorouracil/therapeutic use MH - Gene Amplification MH - Humans MH - *Immunohistochemistry MH - *In Situ Hybridization, Fluorescence/*methods MH - Lymphatic Metastasis MH - Polymerase Chain Reaction MH - Prognosis MH - Randomized Controlled Trials as Topic MH - Receptor, ErbB-2/*metabolism MH - Survival Analysis MH - Treatment Outcome EDAT- 2005/07/05 09:00 MHDA- 2005/07/27 09:00 CRDT- 2005/07/05 09:00 PHST- 2005/07/05 09:00 [pubmed] PHST- 2005/07/27 09:00 [medline] PHST- 2005/07/05 09:00 [entrez] AID - 23/19/4287 [pii] AID - 10.1200/JCO.2005.11.012 [doi] PST - ppublish SO - J Clin Oncol. 2005 Jul 1;23(19):4287-97. doi: 10.1200/JCO.2005.11.012.