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


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.


CONCLUSIONS
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.
Department of Medical Oncology , Zhejiang Cancer Hospital, Hangzhou, China.|Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou, China.
Zhengbo
Z
Song
Department of Medical Oncology , Zhejiang Cancer Hospital, Hangzhou, China.|Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou, China.
Xinmin
X
Yu
Department of Medical Oncology , Zhejiang Cancer Hospital, Hangzhou, China.|Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou, China.
Zhiyong
Z
Shi
Department of Medical Oncology , Zhejiang Cancer Hospital, Hangzhou, China.|Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou, China.
Jun
J
Zhao
Department of Medical Oncology , Zhejiang Cancer Hospital, Hangzhou, China.|Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou, China.
Yiping
Y
Zhang
D044466:Asian People / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
HER2 mutation; genetic variability; non-small cell lung cancer; prevalence; treatment