PRECLINICAL REPORTSPrevalence and influence on outcome of HER2/neu, HER3 and NRG1 expression in patients with metastatic colorectal cancerStahler, Arndta,b; Heinemann, Volkera,d; Neumann, Jensb,d; Crispin, Alexanderc; Schalhorn, Andreasa; Stintzing, Sebastiana,d; Giessen-Jung, Clemensa; Fischer von Weikersthal, Ludwige; Vehling-Kaiser, Ursulaf; Stauch, Martinag; Quietzsch, Detlefh; Holch, Julian W.a; Kruger, Stephana; Haas, Michaela; Michl, Marliesa; von Einem, Jobsta; Kirchner, Thomasb,d; Jung, Andreasb,d; Modest, Dominik P.a,dAuthor Information aDepartment of Medicine III, Comprehensive Cancer Centre, University Hospital Grosshadern bDepartment of Pathology cInstitute of Medical Informatics, Biometry, and Epidemiology, University of Munich dGerman Department of Translational Cancer Research (DKTK), German Cancer Research Centre (DKFZ), Heidelberg eKlinikum St Marien, Oncology, Amberg fOncological surgery, Landshut gCentre of ambulatory treatment for oncological and haematological diseases, Kronach hKlinikum Chemnitz, Chemnitz, Germany Correspondence to Dominik P. Modest, MD, Department of Medicine III, Comprehensive Cancer Centre, University Hospital Grosshadern, Marchioninistrasse 15, Munich D-81377, Germany Tel: +49 89 4400 72208; fax: +49 89 4400 75252/+49 89 7095 5256;e-mail: email@example.com Received March 7, 2017 Accepted April 6, 2017 Anti-Cancer Drugs: August 2017 - Volume 28 - Issue 7 - p 717-722 doi: 10.1097/CAD.0000000000000510 Buy Metrics Abstract Our aim was to explore the impact of the HER2/neu, HER3 receptor as well as their ligands’ neuregulin (NRG1) expression on the outcome of patients with metastatic colorectal cancer (mCRC). NRG1, HER2/neu and HER3 expression was evaluated in 208 patients with mCRC receiving 5-FU/LV plus irinotecan or irinotecan plus oxaliplatin as the first-line treatment. Biomarker expression was correlated with the outcome of patients. NRG1 (low: 192 vs. high: 16), HER2/neu (low: 201 vs. high: 7) and HER3 (low: 69 vs. high: 139) expressions were assessed in 208 patients. High versus low NRG1 expression significantly affected progression-free survival (PFS) [4.7 vs. 8.2 months, hazard ratio (HR): 2.45; 95% confidence interval (CI): 1.45–4.13; P=0.001], but not overall survival (OS) (15.5 vs. 20.7 months, HR: 1.33; 95% CI: 0.76–2.35; P=0.32). High versus low HER3 expression (PFS: 7.1 vs. 8.8 months, HR: 1.11; 95% CI: 0.82–1.50; P=0.50; OS: 19.8 vs. 21.1 months, HR: 0.95; 95% CI: 0.70–1.30; P=0.75) and high compared with low HER2/neu expression (PFS: 7.7 vs. 8.0 months, HR: 1.07; 95% CI: 0.71–1.60; P=0.75; OS: 16.6 vs. 21.1 months, HR: 1.13; 95% CI: 0.75–1.71; P=0.57) did not influence outcome. High NRG1 expression was associated with inferior PFS in the FIRE-1 trial. We did not detect a prognostic impact of HER2/neu and HER3 overexpression in mCRC. The frequency of overexpression was comparable with other studies. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.