Abstract

BackgroundERBB2 (HER2) is a driver gene identified in non-small cell lung cancer (NSCLC). The prevalence, clinicopathology, genetic variability and treatment of HER2-positive NSCLC in Chinese population are unclear.Patients and MethodsEight hundred and fifty-nine patients with pathologically confirmed NSCLC were screened for HER2 mutations using Sanger sequencing. Next-generation sequencing (NGS) was performed in positive cases. HER2 amplification was detected with FISH. Overall survival (OS) was evaluated using Kaplan-Meier methods and compared with log-rank tests.ResultsTwenty-one cases carrying HER2 mutations were identified with a prevalence of 2.4%. HER2 mutations were more frequently encountered in females, non-smokers and adenocarcinoma. NGS was performed in 19 out of 21 patients, The results showed 16 cases with additional genetic aberrations, most commonly associated with TP53 (n = 6), followed by EGFR (n = 3), NF1 (n = 3), KRAS (n = 2) and other mutations. One patient harbored HER2 amplification. Four patients with stage IV received afatinib treatment, and three showed stable disease with a median progression-free survival of 4 months and one patient was diagnosed with progressive disease.ConclusionHER2 mutations represent a distinct subset of NSCLC. NGS showed that HER2 mutations commonly co-existed with other driver genes. Afatinib treatment displayed moderate efficacy in patients with HER2 mutations.

Highlights

  • Lung cancer is one of the leading causes of cancerrelated death worldwide [1]

  • Four patients with stage IV received afatinib treatment, and three showed stable disease with a median progression-free survival of 4 months and one patient was diagnosed with progressive disease

  • HER2 mutations represent a distinct subset of non-small cell lung cancer (NSCLC)

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Summary

Introduction

Testing for driver genes in patients with non-small cell lung cancer (NSCLC) is the new standard of clinical decision-making [2,3]. ERBB2 (HER2) is expressed in solid carcinomas including cancers of the breast, stomach, lung and pancreas [8]. Preclinical and clinical studies have confirmed that HER2 is a driver gene in NSCLC [912]. Three principal mechanisms of HER2 alteration include: protein overexpression, gene amplification and gene mutations [13]. In NSCLC, HER2 mutations were identified to represent a distinct subset of driver genes that usually excluded with other common driver genes like EGFR,KRAS and ALK ,based on published studies. ERBB2 (HER2) is a driver gene identified in non-small cell lung cancer (NSCLC). The prevalence, clinicopathology, genetic variability and treatment of HER2-positive NSCLC in Chinese population are unclear

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