Clinicopathologic Characteristics of Patients with HER2 Insertions in Non-small Cell Lung Cancer

The human epidermal growth factor receptor-2 (HER2) genes have been described in a subset of non-small cell lung cancer (NSCLC). To help identify and treat these patients, we investigated the frequency, clinicopathologic characteristics, and clinical outcomes of patients who had NSCLC with or without HER2 insertions. The mutational status of the HER2 (exons 19-20) gene was assessed in a cohort of 1875 patients with NSCLC. All patients were also analyzed for mutations in EGFR, KRAS, BRAF, ALK, RET, and ROS1. Clinical characteristics, including age, sex, smoking status, stage, histology, tumor size, differentiation, overall survival, and relapse-free survival, were collected. Among 1875 NSCLCs examined, 35 (1.9 %) were HER2 insertion. Compared with the HER2 insertion-negative group, patients with HER2 insertions were more likely to be never smokers (97.1 %, 34/35 patients, P < 0.001), significantly associated with female (91.4 %, 32/35 patients, P < 0.001), adenocarcinoma (91.4 %, 32/35 patients, P = 0.01), and with a tendency to be no more than 60 years of age (71.4 %, 25/35 patients, P = 0.051). HER2 insertion could define a distinct subset of NSCLC, which had a higher prevalence among females, nonsmokers, and adenocarcinoma. HER2 should be in the clinical genotyping of lung cancer, so patients may benefit from HER2-targeted therapy.