HER2 mutations in Chinese patients with non-small cell lung cancer

// Zhengbo Song 1,2 , Xinmin Yu 1,2 , Zhiyong Shi 1,2 , Jun Zhao 1,2 and Yiping Zhang 1,2 1 Department of Medical Oncology , Zhejiang Cancer Hospital, Hangzhou, China 2 Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou, China Correspondence to: Yiping Zhang, email: // Keywords : non-small cell lung cancer, HER2 mutation, prevalence, genetic variability, treatment Received : November 14, 2015 Accepted : July 27, 2016 Published : August 16, 2016 Abstract Background: 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. Patients and Methods: Eight 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. Results: Twenty-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. Conclusion: HER2 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.