title: Relationships between serum HER2 ECD, TIMP-1 and clinical outcomes in Taiwanese breast cancer.
abstract: BACKGROUND
  Serum levels of the extracellular domain of HER2/neu (HER2 ECD) have been demonstrated to be associated with clinical outcomes. A disintegrin and metalloproteinase-10, a sheddase of HER2/neu, can drive cancer progression and its activity is inhibited by tissue inhibitor of metalloproteinase-1 (TIMP-1). However, elevated TIMP-1 expression has been associated with a poor prognosis of breast cancer. Therefore, this study was performed to explore the relationships between serum HER2 ECD, TIMP-1 and clinical outcomes.
  
  
  METHODS
  One hundred and eighty-five female breast cancer patients, who received curative mastectomy without neo-adjuvant chemotherapy at Chang-Gung Memorial Hospital, were recruited with informed consent for this study. Pre-operative serum levels of HER2 ECD and TIMP-1 were measured using an enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Twenty-three cases (12.4%) were classified HER2 ECD positive. HER2 ECD positivity was significantly associated with age, lymph node involvement, histological grade, estrogen receptor status, progesterone receptor status, tissue HER2/neu overexpression, and disease-free survival (DFS). In an age, stage, ER and HER2/neu status matched subgroup (N = 41), the serum level of TIMP-1 was significantly associated with HER2 ECD positivity and DFS.
  
  
  CONCLUSIONS
  A high serum TIMP-1 was significantly associated with HER2 ECD positivity and a poorer DFS among Taiwanese primary breast cancer patients with HER2 overexpression.
authors.affiliation: Graduate Institute of Clinical Medical Sciences,Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Hsiu-Pei
authors.initials: HP
authors.lastname: Tsai
authors.forename: Shin-Cheh
authors.initials: SC
authors.lastname: Chen
authors.forename: Huei-Tzu
authors.initials: HT
authors.lastname: Chien
authors.forename: Yi-Yin
authors.initials: YY
authors.lastname: Jan
authors.forename: Tzu-Chieh
authors.initials: TC
authors.lastname: Chao
authors.forename: Miin-Fu
authors.initials: MF
authors.lastname: Chen
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Hsieh
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000401:mortality* / Q000628:therapy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D012189:Retrospective Studies; D015996:Survival Rate; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D019715:Tissue Inhibitor of Metalloproteinase-1; C560822:TIMP1 protein, human; C508053:ERBB2 protein, human