title: The efficacy of trastuzumab in Her-2/neu-overexpressing metastatic breast cancer is independent of p53 status.
abstract: OBJECTIVE
  Her-2/neu and p53-mediated signalling have been shown to interact at various cellular levels. However, the clinical relevance of p53 alterations in patients receiving trastuzumab for Her-2/neu-overexpressing metastatic breast cancer (MBC) remains unknown. The present study was performed to corroborate previous in vitro findings from our laboratory showing that trastuzumab induces growth arrest and apoptosis in a p53-independent manner.
  
  
  METHODS
  Retrospective immunohistochemical (IHC) analysis for p53 protein expression was carried out on tumour specimens from 104 patients receiving trastuzumab-based treatment for Her-2/neu-overexpressing MBC at a single institution. p53 status was correlated with response (R) and clinical benefit (CB), median progression-free survival (PFS) time and overall survival (OAS) time in univariate and multivariate analyses.
  
  
  RESULTS
  Characteristics were similar between p53-negative and p53-positive tumours (all P>0.05). In univariate analyses, R (39% vs 26%, P=0.208), CB (70% vs 57%, P=0.218), PFS (6.2 months vs 4.2 months, P=0.186) and OAS (23.8 months vs 23.2 months, P=0.650) were similar for p53-positive tumours and p53-negative tumours, respectively. In multivariate analyses, p53 status was not a significant predictor of R, CB, PFS or OAS (all P>0.05).
  
  
  CONCLUSIONS
  p53 status, as determined by IHC, is not a predictor of the clinical efficacy of trastuzumab-based treatment in patients with Her-2/neu-overexpressing MBC.
authors.affiliation: Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, 18-20 Waehringer Guertel, 1090, Vienna, Austria. wolfgang.koestler@meduniwien.ac.at
authors.forename: Wolfgang J
authors.initials: WJ
authors.lastname: Köstler
authors.forename: Thomas
authors.initials: T
authors.lastname: Brodowicz
authors.forename: Gernot
authors.initials: G
authors.lastname: Hudelist
authors.forename: Margaretha
authors.initials: M
authors.lastname: Rudas
authors.forename: Reinhard
authors.initials: R
authors.lastname: Horvat
authors.forename: Günther G
authors.initials: GG
authors.lastname: Steger
authors.forename: Christian F
authors.initials: CF
authors.lastname: Singer
authors.forename: Johannes
authors.initials: J
authors.lastname: Attems
authors.forename: Werner
authors.initials: W
authors.lastname: Rabitsch
authors.forename: Negar
authors.initials: N
authors.lastname: Fakhrai
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Elandt
authors.forename: Christoph
authors.initials: C
authors.lastname: Wiltschke
authors.forename: Michael
authors.initials: M
authors.lastname: Hejna
authors.forename: Christoph C
authors.initials: CC
authors.lastname: Zielinski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D005260:Female; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate; D000068878:Trastuzumab; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D016159:Tumor Suppressor Protein p53