The efficacy of trastuzumab in Her-2/neu-overexpressing metastatic breast cancer is independent of p53 status (2005)

Author(s): Kostler WJ, Brodowicz T, Hudelist G, Rudas M, Horvat R, Steger GG, Singer CF, Attems J, Rabitsch W, Fakhrai N, Elandt K, Wiltschke C, Hejna M, Zielinski CC

    Abstract: PURPOSE: 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. METHOD: 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.

    Notes: Kostler, Wolfgang J Brodowicz, Thomas Hudelist, Gernot Rudas, Margaretha Horvat, Reinhard Steger, Gunther G Singer, Christian F Attems, Johannes Rabitsch, Werner Fakhrai, Negar Elandt, Katarzyna Wiltschke, Christoph Hejna, Michael Zielinski, Christoph C Comparative Study Germany Journal of cancer research and clinical oncology J Cancer Res Clin Oncol. 2005 Jul;131(7):420-8. Epub 2005 Apr 29.

      • Date: 01-07-2005
      • Journal: Journal of Cancer Research and Clinical Oncology
      • Volume: 131
      • Issue: 7
      • Pages: 420-428
      • Publisher: Springer
      • Publication type: Article
      • Bibliographic status: Published

      Keywords: Adult Aged Aged, 80 and over Antibodies, Monoclonal/*therapeutic use Antineoplastic Agents/*therapeutic use Breast Neoplasms/*drug therapy/metabolism/secondary Carcinoma, Ductal, Breast/*drug therapy/metabolism/secondary Female Humans Middle Aged Prognosis Receptor, erbB-2/*metabolism Retrospective Studies Survival Rate Treatment Outcome Tumor Markers, Biological/*metabolism Tumor Suppressor Protein p53/*metabolism Up-Regulation


      Professor Johannes Attems
      Professor of Neuropathology, Honorary Consultant Pathologist