|Association between the HER2 Ile655Val polymorphism and response to trastuzumab in women with operable primary breast cancer|
|Han, X.1; Diao, L.1; Xu, Y.1; Xue, W.2; Ouyang, T.1; Li, J.1; Wang, T.1; Fan, Z.1; Fan, T.1; Lin, B.1; Xie, Y.1|
|关键词||HER2 gene polymorphism trastuzumab breast cancer response|
|刊名||ANNALS OF ONCOLOGY|
|WOS标题词||Science & Technology|
|关键词[WOS]||ADJUVANT CHEMOTHERAPY ; GENETIC-POLYMORPHISM ; OPEN-LABEL ; CODON 655 ; RISK ; MULTICENTER ; ONCOGENE ; EFFICACY ; ANTIBODY ; THERAPY|
Human epidermal growth factor receptor 2 (HER2) Ile655Val polymorphism may affect the efficacy of trastuzumab treatment of breast cancer.
HER2 Ile655Val polymorphism was determined in 4167 patients with primary breast cancer using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. We investigated the associations between the HER2 Ile655Val polymorphism and clinical outcomes in women with HER2-negative breast cancer and with HER2-positive breast cancer who received trastuzumab or who did not.
At a median follow-up of 44 months, HER2 Ile655Val polymorphism was not significantly associated with survival either in the entire study population of 4167 patients or in 2976 HER2-negative breast cancer patients. Among 816 HER2-positive patients who received adjuvant chemotherapy and/or endocrine therapy without trastuzumab treatment, patients with the Val/Ile or the Val/Val genotype had a significantly worse disease-free survival (DFS) and distant DFS (DDFS) than those with the Ile/Ile genotype (DFS, adjusted hazard ratio [HR] 1.5; 95% confidence interval [CI] 1.0-2.3; P = 0.037; DDFS, adjusted HR 1.9; 95% CI 1.2-2.9 P = 0.005). In contrast, among 212 HER2-positive patients who received chemotherapy in combination with trastuzumab treatment, patients with the Val/Ile or the Val/Val genotype had a significantly better DFS and DDFS than those with the Ile/Ile genotype (5-year DFS, 100% versus 83%; P = 0.008; 5-year DDFS, 100% versus 89%; P = 0.031).
HER2 Ile655Val polymorphism affects the function of HER2 gene only restricted in HER2-positive breast cancers. HER2-positive breast cancer patients with the Val variant have an aggressive phenotype, but are sensitive to trastuzumab treatment.
|项目编号||2013CB9 ; 30973436 ; 81071629|
|资助机构||973 project ; program for Breast Cancer Tissue Bank of Beijing ; National Natural Science Foundation of China|
|作者单位||1.Peking Univ, Breast Ctr, Canc Hosp & Inst, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing 100142, Peoples R China|
2.Peking Univ, Dept Pathol, Canc Hosp & Inst, Beijing 100142, Peoples R China
|Han, X.,Diao, L.,Xu, Y.,et al. Association between the HER2 Ile655Val polymorphism and response to trastuzumab in women with operable primary breast cancer[J]. ANNALS OF ONCOLOGY,2014,25(6):1158-1164.|
|APA||Han, X..,Diao, L..,Xu, Y..,Xue, W..,Ouyang, T..,...&Xie, Y..(2014).Association between the HER2 Ile655Val polymorphism and response to trastuzumab in women with operable primary breast cancer.ANNALS OF ONCOLOGY,25(6),1158-1164.|
|MLA||Han, X.,et al."Association between the HER2 Ile655Val polymorphism and response to trastuzumab in women with operable primary breast cancer".ANNALS OF ONCOLOGY 25.6(2014):1158-1164.|