title: Prognostic value of HER3, PTEN and p-HER2 expression in patients with HER2positive breast cancer.
abstract: BACKGROUND
  HER2 overexpression is an unfavorable prognostic factor in patients with breast cancer, but it is also a target for the monoclonal antibody trastuzumab, which is effective in adjuvant and palliative settings. HER2 positivity is an inclusion criterion for immunotherapy, but it is not a positive predictive factor, and only half of patients benefit from the treatment.
  
  
  OBJECTIVE
  The aim of this study was to evaluate the prognostic and predictive value of HER3, PTEN and phosphorylated HER2 (p-HER2) expression in primary breast tumors of patients treated with trastuzumab in an adjuvant or palliative regimen.
  
  
  METHODS
  Immunohistochemical (IHC) analysis with 3 antibodies specific to the proteins was performed in tumor specimens obtained from 81 HER2-positive patients treated with trastuzumab.
  
  
  RESULTS
  HER3 overexpression was present in 55.6% of the examined tumors, and PTEN or pHER2 positivity was present in 32.0% and 34.6% of them, respectively. HER3 overexpression and PTEN positivity correlated with larger tumor size (p=0.016 and p=0.008, respectively). p-HER2 positivity correlated with more advanced clinical stage of the disease (p=0.032). There was no correlation between the proteins' expression and survival for 31 patients treated with trastuzumab in the palliative regimen.
  
  
  CONCLUSIONS
  HER3 overexpression, PTEN positivity and p-HER2 positivity in tumor cells of HER2-positive patients correlate with more advanced clinical stage of breast cancer. Expression of these proteins does not predict outcome of trastuzumab treatment.
authors.affiliation: Department of Chemotherapy, Medical University of Łódź, Copernicus Memorial Hospital, Łódź, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Dębska-Szmich
authors.affiliation: Department of Pathology, Medical University of Łódź, Łódź, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Kusińska
authors.affiliation: Department of Chemotherapy, Medical University of Łódź, Copernicus Memorial Hospital, Łódź, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Czernek
authors.affiliation: Department of Chemotherapy, Medical University of Łódź, Copernicus Memorial Hospital, Łódź, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Szydłowska-Pazera
authors.affiliation: Department of Chemotherapy, Medical University of Łódź, Copernicus Memorial Hospital, Łódź, Poland.
authors.forename: Maja
authors.initials: M
authors.lastname: Habib-Lisik
authors.affiliation: Department of Surgical Oncology, Medical University of Łódź, Copernicus Memorial Hospital, Łódź, Poland.
authors.forename: Janusz H
authors.initials: JH
authors.lastname: Piekarski
authors.affiliation: Department of Pathology, Copernicus Memorial Hospital, Łódź, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Olas
authors.affiliation: Department of Pathology, Polish Mother Memorial Hospital, Łódź, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kulig
authors.affiliation: Department of Chemotherapy, Copernicus Memorial Hospital, Łódź, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Ułańska
authors.affiliation: Department of Chemotherapy, Copernicus Memorial Hospital, Łódź, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Kalinka-Warzocha
authors.affiliation: Department of Chemotherapy, Medical University of Łódź, Copernicus Memorial Hospital, Łódź, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Potemski
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D010766:Phosphorylation; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000235:genetics*; D000068878:Trastuzumab / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D051059:PTEN Phosphohydrolase; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C581292:ERBB3 protein, human; C494929:PTEN protein, human