title: HER2 mutation status in Japanese HER2-negative breast cancer patients.
abstract: OBJECTIVE
  Human epidermal growth factor receptor 2 (HER2) gene amplification is a major therapeutic target in breast cancer, and has been introduced as a predictive biomarker to identify patients who may benefit from therapy with anti-human epidermal growth factor receptor 2 agents. Human epidermal growth factor receptor 2 somatic mutations have been reported in patients without human epidermal growth factor receptor 2 gene amplification. Since these are activating mutations, these patients may also benefit from human epidermal growth factor receptor 2-targeted drugs.
  
  
  METHODS
  In this study, we searched for human epidermal growth factor receptor 2 mutations in a group of 286 Japanese breast cancer patients with human epidermal growth factor receptor 2-negative tumors. The activating mutations of human epidermal growth factor receptor 2 identified were analyzed by direct Sanger sequencing of two major areas: the extracellular domain at 309-310 and the kinase domain between 755 and 781.
  
  
  RESULTS
  Two tumors were found to have a human epidermal growth factor receptor 2 somatic mutation; one with I767M mutation and another with D769Y. No mutation was observed in the extracellular domain. One of these patients with human epidermal growth factor receptor 2 mutation recurred early with liver metastasis.
  
  
  CONCLUSIONS
  Better knowledge of human epidermal growth factor receptor 2 mutation status will help us to choose personalized molecular targeted therapy for use in human epidermal growth factor receptor 2-negative Japanese breast cancer patients.
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Endo
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya.
authors.forename: Yu
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya.
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Yoshimoto
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Asano
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Hato
authors.affiliation: Department of Breast and Endocrine Surgery, Hokkaido University Hospital, Sapporo.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Yamashita
authors.affiliation: Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Sato
authors.affiliation: Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fujii
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya t.toyama@med.nagoya-cu.ac.jp.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Toyama
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology; D044466:Asian People / Q000706:statistics & numerical data*; D001224:Aspartic Acid; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007532:Isoleucine; D007564:Japan / Q000453:epidemiology; D008715:Methionine; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009154:Mutation / Q000187:drug effects; D060787:Neoplasm Grading; D016133:Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014443:Tyrosine
chemical_list: D000970:Antineoplastic Agents; D001224:Aspartic Acid; D014408:Biomarkers, Tumor; D007532:Isoleucine; D008715:Methionine; D018719:Erb-b2 Receptor Tyrosine Kinases; D014443:Tyrosine; C508053:ERBB2 protein, human
keywords: DNA sequencing; HER2; Japanese; breast cancer; genes; mutation