Quantitative detection of HER2 protein concentration in breast cancer tissue does not increase the number of patients eligible for adjuvant HER2-targeted therapy

Bechmann,Troels; Olsen,Dorte  Aalund; Jakobsen,Erik  Hugger; Madsen,Jonna  Skov; Brandslund,Ivan; Jylling,Anne  Marie Bak; Steffensen,Karina  Dahl; Jakobsen,Anders

doi:10.3892/or.2013.2289

Quantitative detection of HER2 protein concentration in breast cancer tissue does not increase the number of patients eligible for adjuvant HER2-targeted therapy

Authors:
- Troels Bechmann
- Dorte Aalund Olsen
- Erik Hugger Jakobsen
- Jonna Skov Madsen
- Ivan Brandslund
- Anne Marie Bak Jylling
- Karina Dahl Steffensen
- Anders Jakobsen
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Affiliations: Department of Oncology, Vejle Hospital, Vejle, Denmark, Department of Biochemistry, Vejle Hospital, Vejle, Denmark, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark, Department of Pathology, Odense University Hospital, Odense, Denmark
Published online on: February 15, 2013 https://doi.org/10.3892/or.2013.2289
Pages: 1475-1482

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Abstract

Human epidermal growth factor receptor-2 (HER2) is overexpressed in 15-20% of breast cancer patients and is associated with an aggressive tumor and a poor prognosis. Currently, patients are selected for adjuvant HER2-targeted therapy based on HER2 status by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). In this study, we assessed the clinical significance of tissue HER2 status determined by a quantitative immunoassay using ADVIA Centaur. We investigated the hypothesis that the clinical outcome is worse in a group of patients defined as tissue HER2-positive only by Centaur, but not treated with adjuvant HER2-targeted therapy, compared to patients defined as HER2-positive by IHC/FISH and therefore treated with adjuvant HER2-targeted therapy. Tumor tissue was obtained at primary surgery from 415 breast cancer patients between 2004 and 2010. HER2 status was determined by quantitative immunoassay of fresh-frozen tissue and by IHC/FISH of corresponding paraffin-embedded tissue. We compared the clinical outcome in four groups of patients defined by tissue HER2 status and adjuvant HER2-targeted therapy. The final analysis included 379 patients after a median follow-up of 3.9 years for invasive disease-free survival (IDFS) and 4.2 years for overall survival (OS). The quantitative Centaur assay defined a greater number of patients (100 patients, 26.4%) as HER2-positive than IHC/FISH (63 patients, 16.6%) (P<0.0001). No significant difference in IDFS (P=0.159) and OS (P=0.150) was observed among the four groups of patients. However, in the IHC/FISH-positive group without adjuvant HER2-targeted therapy (group 2), a significantly greater number of events was found compared to the Centaur-positive group without adjuvant HER2-targeted therapy (group 3) for both IDFS (P=0.025) and OS (P=0.020). Quantitative HER2 determination by Centaur did not define a new group of patients eligible for HER2-targeted therapy. Currently, tissue HER2 status defined by IHC/FISH analysis remains the gold standard.

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