Purpose: 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 HER2-targeted therapy. The aim of this study was to survey the proportion of patients who had HER2 aberration and to investigate the correlation between HER2 amplification and HER2 overexpression in immunohistochemistry (IHC) as a real-world data.
Methods: We surveyed the incidence of HER2 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.
Results: Of 2,119 patients with cancer, 189 patients (8.9%) had HER2 aberration in their tumor specimen. Of 189 patients, 113 (5.3%) patients had HER2 amplification, 82 (3.9%) patients had HER2 mutations, and 11 (0.5%) patients had HER2 fusion. Of note, 10 patients (0.5%) had concurrent HER2 amplification and HER2 fusion. In addition, we identified that HER2 protein overexpression was strongly related to HER2 amplification by NGS. Of 74 patients with HER2 amplification only by NGS test, 64 patients (86.5%) had HER2 overexpression by IHC. Of 10 patients with concurrent HER2 amplification and fusion, 80% patients were HER2 overexpression. Among 51 patients with only HER2 mutation (SNV), 9 patients (17.6%) were HER2 (+). Interestingly, almost all patients with colorectal cancer (11 of 12) with HER2 amplification had very strong HER2 overexpression (3+) in their tumor specimen.
Conclusion: In conclusion, we showed that when patients with metastatic cancer receive NGS test, approximately 8.9% have HER2 aberrations in their tumor specimen. Most patients have HER2 amplification, and a small percentage of patients have HER2 fusion. A great majority of patients with HER2 amplification and/or HER2 fusion had HER2 (+) tumor by IHC.