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

Lookup NU author(s): Professor Johannes Attems


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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.

Publication metadata

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

Publication type: Article

Publication status: Published

Journal: Journal of Cancer Research and Clinical Oncology

Year: 2005

Volume: 131

Issue: 7

Pages: 420-428

ISSN (print): 0171-5216

ISSN (electronic): 1432-1335

Publisher: Springer


DOI: 10.1007/s00432-005-0670-3

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.


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