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

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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.

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Acknowledgements

The authors gratefully acknowledge the assistance of Dr. Ernst Rücklinger for statistical analyses and Dr. Angelika Eiper for logistic support. In addition, we would like to thank the following collaborators (in alphabetical order) who provided us with histology samples: W. Adolf, H. Bankl, I. Brandl, H. Brustmann, J. Feichtinger, L. Gerstner, T. Kessler, M. Klimpfinger, K. Kofler, D. Kosak, S. Naude, W. Rausch, A. Soleiman, W. Ulrich, S. Wuketich.

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  1. Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, 18-20 Waehringer Guertel, 1090, Vienna, Austria

    Wolfgang J. Köstler, Thomas Brodowicz, Günther G. Steger, Negar Fakhrai, Katarzyna Elandt, Christoph Wiltschke, Michael Hejna & Christoph C. Zielinski

  2. Center of Excellence for Clinical & Experimental Oncology (CLEXO), Medical University of Vienna, Vienna, Austria

    Wolfgang J. Köstler, Thomas Brodowicz, Günther G. Steger, Christian F. Singer, Werner Rabitsch, Negar Fakhrai, Katarzyna Elandt, Christoph Wiltschke, Michael Hejna & Christoph C. Zielinski

  3. Ludwig Boltzmann Institute for Clinical Experimental Oncology, Medical University of Vienna, Vienna, Austria

    Gernot Hudelist & Christoph C. Zielinski

  4. Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria

    Margaretha Rudas & Reinhard Horvat

  5. Clinical Division of Special Gynecology, Department of Gynecology and Obstetrics, Medical University of Vienna, Vienna, Austria

    Christian F. Singer

  6. Department of Pathology, Otto Wagner Hospital, Vienna, Austria

    Johannes Attems

  7. Bone Marrow Transplantation Unit, Department of Medicine I, Medical University of Vienna, Vienna, Austria

    Werner Rabitsch

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  1. Wolfgang J. Köstler
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Correspondence to Wolfgang J. Köstler.

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Köstler, W.J., Brodowicz, T., Hudelist, G. et al. The efficacy of trastuzumab in Her-2/neu-overexpressing metastatic breast cancer is independent of p53 status. J Cancer Res Clin Oncol 131, 420–428 (2005). https://doi.org/10.1007/s00432-005-0670-3

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