title: Association between the HER2 Ile655Val polymorphism and response to trastuzumab in women with operable primary breast cancer.
abstract: BACKGROUND
  Human epidermal growth factor receptor 2 (HER2) Ile655Val polymorphism may affect the efficacy of trastuzumab treatment of breast cancer.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Breast Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing.
authors.forename: X
authors.initials: X
authors.lastname: Han
authors.affiliation: Breast Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing.
authors.forename: L
authors.initials: L
authors.lastname: Diao
authors.affiliation: Breast Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing.
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, PR China.
authors.forename: W
authors.initials: W
authors.lastname: Xue
authors.affiliation: Breast Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing.
authors.forename: T
authors.initials: T
authors.lastname: Ouyang
authors.affiliation: Breast Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Breast Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing.
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.affiliation: Breast Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing.
authors.forename: Z
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Breast Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing.
authors.forename: T
authors.initials: T
authors.lastname: Fan
authors.affiliation: Breast Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing.
authors.forename: B
authors.initials: B
authors.lastname: Lin
authors.affiliation: Breast Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing zlxyt2@bjmu.edu.cn.
authors.forename: Y
authors.initials: Y
authors.lastname: Xie
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: HER2 gene; breast cancer; polymorphism; response; trastuzumab