HER2 amplification level is not a prognostic factor for HER2-positive breast cancer with trastuzumab-based adjuvant treatment: a systematic review and meta-analysis.

Qian-Qian Xu,Ying Zhong,Feng Mao,Yi-Dong Zhou,Yan-Na Zhang,Jing-Hong Guan,Xue-Jing Wang,Qiang Sun,Ya-Li Xu,Chang-Jun Wang,Song-Jie Shen,Yan Lin,Xiao-Hui Zhang,Bo Pan

doi:10.18632/oncotarget.11541

Abstract

BackgroundTrastuzumab-based therapy is a standard, targeted treatment for HER2-positive breast cancer in the adjuvant setting. However, patients do not benefit equally from it and the association between HER2 amplification level and patients' survival remains controversial. A systematic review and meta-analysis was conducted by incorporating all available evidence to evaluate the association between disease free survival (DFS) and HER2 amplification level.ResultsThree cohort studies involving 1360 HER2-positive breast cancer patients stratified by HER2 amplification magnitude were eligible for meta-analysis. The combined HRs for DFS were 1.05 (95% CI: 0.80−1.36, p = 0.74) and 0.97 (95% CI: 0.73−1.29, p = 0.83) for HER2 gene copy number (GCN) and HER2/CEP 17 ratio. No evidence of heterogeneity or public bias was found.MethodsDatabases including PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL), were searched for eligible literature. HER2 amplification level was evaluated by fluorescence in situ hybridization (FISH) in terms of gene copy number (GCN) and HER2/CEP17 ratio. Hazard ratios (HRs) for DFS with 95% confidence interval (CI) according to the amplification level of HER2 were extracted. The outcomes were synthesized based on a fixed-effects model.ConclusionsHER2 amplification level is not a prognostic factor for HER2-positive breast cancer with trastuzumab-based targeted therapy in the clinical adjuvant setting.

Highlights

The human epidermal growth factor receptor 2 (HER2) is a 185-kd glycoprotein with tyrosine kinase activity
Three cohort studies involving 1360 HER2-positive breast cancer patients stratified by HER2 amplification magnitude were eligible for meta-analysis
The combined Hazard ratios (HRs) for disease free survival (DFS) were 1.05 and 0.97 for HER2 gene copy number (GCN) and HER2/CEP 17 ratio

Summary

Introduction

The human epidermal growth factor receptor 2 (HER2) is a 185-kd glycoprotein with tyrosine kinase activity. HER2 positivity has been shown to confer an adverse prognosis [1,2,3] and serve as a predictor of clinical response to treatment with the humanized monoclonal antibody trastuzumab [4, 5]. Trastuzumab shows considerable clinical efficacy and extends the overall survival of certain patients with HER2-positive breast cancer [6,7,8,9,10]. Studies have been conducted to investigate the relationship between HER2 status and response to trastuzumab or clinical outcomes in HER2-positive breast cancer cohorts with trastuzumab-containing treatment. All included participants were HER2-positive breast cancer patients who received trastuzumab-based therapy according to the standard dose regimen. Trastuzumab-based therapy is a standard, targeted treatment for HER2-positive breast cancer in the adjuvant setting. A systematic review and meta-analysis was conducted by incorporating all available evidence to evaluate the association between disease free survival (DFS) and HER2 amplification level

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Results

Conclusion