Clinical Implication of <i>HER2</i> Aberration in Patients With Metastatic Cancer Using Next-Generation Sequencing: A Pan-Tumor Analysis.

Abstract

Human epidermal growth factor receptor 2 (HER2) protein expression or gene amplification is a significant predictive biomarker for identifying patients with cancer, who may benefit from <i>HER2</i>-targeted therapy. The aim of this study was to survey the proportion of patients who had <i>HER2</i> aberration and to investigate the correlation between <i>HER2</i> amplification and HER2 overexpression in immunohistochemistry (IHC) as a real-world data. We surveyed the incidence of <i>HER2</i> aberration including mutation (single-nucleotide variant [SNV]), amplification (copy-number variation), and fusion by next-generation sequencing (NGS) in 2,119 patients with cancer from Samsung Medical Center in South Korea. Of 2,119 patients with cancer, 189 patients (8.9%) had <i>HER2</i> aberration in their tumor specimen. Of 189 patients, 113 (5.3%) patients had <i>HER2</i> amplification, 82 (3.9%) patients had <i>HER2</i> mutations, and 11 (0.5%) patients had <i>HER2</i> fusion. Of note, 10 patients (0.5%) had concurrent <i>HER2</i> amplification and <i>HER2</i> fusion. In addition, we identified that HER2 protein overexpression was strongly related to <i>HER2</i> amplification by NGS. Of 74 patients with <i>HER2</i> amplification only by NGS test, 64 patients (86.5%) had HER2 overexpression by IHC. Of 10 patients with concurrent <i>HER2</i> amplification and fusion, 80% patients were HER2 overexpression. Among 51 patients with only <i>HER2</i> mutation (SNV), 9 patients (17.6%) were HER2 (+). Interestingly, almost all patients with colorectal cancer (11 of 12) with <i>HER2</i> amplification had very strong HER2 overexpression (3+) in their tumor specimen. In conclusion, we showed that when patients with metastatic cancer receive NGS test, approximately 8.9% have <i>HER2</i> aberrations in their tumor specimen. Most patients have <i>HER2</i> amplification, and a small percentage of patients have <i>HER2</i> fusion. A great majority of patients with <i>HER2</i> amplification and/or <i>HER2</i> fusion had HER2 (+) tumor by IHC.