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Background: HER2 positivity is most frequently assessed by a combination of immunohistochemical (IHC) and in situ hybridization (ISH) testing. We previously reported (Dowsett et al, J Clin Oncol, 2009, 27, 2962) in the HERA trial that the degree of benefit from trastuzumab in the 1 year arm and the prognosis in the no-trastuzumab (observation) arm was unaffected by the level of HER2 amplification above the cut-off of 2.0 (HER2/CEP17 ratio). We have now assessed whether IHC staining intensity, which is a measure of the protein target for trastuzumab, had an effect on prognosis or benefit from treatment. Patients and method: 3,401 patients were HER2 positive either by being assessed as IHC 3+ positive or with a FISH ratio of >2.0 in the central laboratory for the HERA trial (Kassel, Germany). We conducted a case-control analysis in which 425 patients were identified as the cases by their experiencing a disease-free survival (DFS) event in the 1-year (n=168) or observation (n=257) arms after a median 2 years’ follow-up. The cases were matched to controls (850 controls, 1:2 ratio). Images were collected using the Ariol image analysis system (Genetix Ltd.) of tissue sections stained by the DAKO HercepTest in the central laboratory. Images were analysed for degree of staining intensity which was quantified as a continuous variable. Relationship of staining intensity with FISH copy number and FISH HER2/CEP17 ratio were assessed. The impact of HER2 staining intensity on risk of a disease-free event was determined using a conditional logistic regression model in SAS 9.2. Results: Image intensity results were available on 381 (89.6%) cases and 755 (88.8%) controls. There were highly significant correlations between HER2 staining intensity and copy number in the whole population (Spearman Correlation, r=0.464, P Conclusion: In tumours overexpressing HER2, gene copy number is more significantly related to IHC staining intensity than HER2/CEP17 ratio. Like degree of amplification, IHC staining intensity does not relate to prognosis of HER2 positive chemotherapy-treated patients or to the benefit they derive from 1 year of adjuvant trastuzumab. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD10-01.