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Clinical significance of quantitative HER2 gene amplification as related to its predictive value in breast cancer patients in neoadjuvant setting

Authors :
Wu,Ziping
Xu,Shuguang
Zhou,Liheng
Yin,Wenjin
Lin,Yanpin
Du,Yueyao
Wang,Yaohui
Jiang,Yiwei
Yin,Kai
Zhang,Jie
Lu,Jinsong
Source :
OncoTargets and Therapy.
Publication Year :
2018
Publisher :
Dove Press, 2018.

Abstract

Ziping Wu,1,* Shuguang Xu,1,* Liheng Zhou,1 Wenjin Yin,2 Yanpin Lin,1 Yueyao Du,1 Yaohui Wang,1 Yiwei Jiang,1 Kai Yin,1 Jie Zhang,1 Jinsong Lu1 1Department of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: The aims of this study were to determine whether the quantitative HER2 gene amplification level is related to the key clinicopathological features that represent the aggressiveness of breast cancer (BC) and to determine whether the quantitative HER2 gene amplification level could predict the treatment response in the subset of HER2-positive patients who received neoadjuvant targeted therapy.Materials and methods: Patients treated with weekly cisplatin- and paclitaxel-based neoadjuvant chemotherapy, who had undergone both immunohistochemistry and the fluorescence in situ hybridization test for HER2, were included in the study (n=103). For HER2-positive patients, defined as immunohistochemistry score 3+ or fluorescence in situ hybridization ratio ≥2.0, trastuzumab was recommended with neoadjuvant chemotherapy (n=45). Pathological complete response was defined as complete pathological remission of tumor cells both in breast and axillary lymph nodes postoperation.Results: In all patients enrolled in the study, a higher HER2 amplification level was significantly correlated with larger tumor size and the absence of ER and PR expression. In HER2-positive patients treated with neoadjuvant trastuzumab concurrent with chemotherapy, both univariate and multivariate logistic regression showed that a higher HER2/CEP17 ratio and HER2 gene copy number were associated with a higher pathological complete response rate. When calculated by receiver operating characteristics analysis, an optimal cutoff of 4.5 for the HER2/CEP17 ratio was expected to distinguish the most sensitive candidate for treatment with a combination of trastuzumab and neoadjuvant chemotherapy.Conclusion: A higher HER2 amplification level was correlated with larger tumor size and reduced ER and PR expression, which may indicate more aggressive tumor behavior. For HER2-positive patients, the HER2/CEP17 ratio and HER2 gene copy number may be good predictive factors for concurrent neoadjuvant trastuzumab and chemotherapy. Keywords: breast cancer, neoadjuvant, quantitative HER2 gene amplification, pathological complete response, predictive

Details

Language :
English
ISSN :
11786930
Database :
OpenAIRE
Journal :
OncoTargets and Therapy
Accession number :
edsair.dovemedicalp..60e85581d374e074509be7eb2b390839