title: Quantitative detection of HER2 protein concentration in breast cancer             tissue does not increase the number of patients eligible for adjuvant HER2-targeted             therapy.
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.
authors: The Faculty of Health Sciences, University of Southern Denmark, and Department of Pathology, Odense University Hospital, Odense, Denmark. troels.bechmann@slb.regionsyddanmark.dk
authors: Troels
authors: T
authors: Bechmann
authors: Dorte Aalund
authors: DA
authors: Olsen
authors: Erik Hugger
authors: EH
authors: Jakobsen
authors: Jonna Skov
authors: JS
authors: Madsen
authors: Ivan
authors: I
authors: Brandslund
authors: Anne Marie Bak
authors: AM
authors: Jylling
authors: Karina Dahl
authors: KD
authors: Steffensen
authors: Anders
authors: A
authors: Jakobsen
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D016612:Paraffin Embedding; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human