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p53 expression and resistance against paclitaxel in patients with metastatic breast cancer

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Abstract

Purpose

Paclitaxel is an important agent in the pharmacological treatment of metastatic breast cancer. Despite its efficacy in selected patients, the majority of patients have a resistance against paclitaxel. The aim of this study was to identify the responding patients and hence prevent the other patients from ineffective treatment. Identifying these patients could spare them an ineffective treatment and could in turn characterize a subgroup of patients with a higher response rate.

Material and methods

Thirty-three patients with metastatic breast cancer received paclitaxel 175 mg/m2 either as first- (15 patients) or as second-line (18 patients) treatment. Immunohistochemistry was performed on the blocks of the primary tumors with monoclonal antibodies against p53, HER-2/neu, P-glycoprotein, Glutathione-S-Transferase-π, and β-tubulin II. The expression of those factors was then correlated with the objective response to paclitaxel.

Results

Ten of 33 patients had an objective response to treatment. A significant correlation with the objective response was found for the expression of p53. None of the tumors with p53 expression (n=11) responded to paclitaxel. In contrast, 10 of the 22 patients without p53 expression showed an objective response (P=0.013). Expression of HER-2/neu, P-glycoprotein, Glutathione-S-Transferase-π, and β-tubulin II did not show a correlation with the response to paclitaxel.

Conclusion

The immunohistochemical detection of p53 characterizes patients with metastatic breast cancer unlikely to respond to paclitaxel.

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Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, University Hospital Mainz, Langenbeckstrasse 1, 55131 , Mainz, Germany

    M. Schmidt, A. Bachhuber, E. Steiner, M. Mahlke, H. Pilch, W. Weikel & P. G. Knapstein

  2. Department of Pathology, University Hospital Mainz, Langenbeckstrasse 1, 55131 , Mainz, Germany

    H. A. Lehr

  3. Institute of Medical Biostatistics, Epidemiology and Informatics, University of Mainz, Mainz, Germany

    A. Victor

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  1. M. Schmidt
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  2. A. Bachhuber
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  3. A. Victor
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  9. P. G. Knapstein
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Correspondence to M. Schmidt.

Additional information

This study was supported in part by a grant from Bristol Myers Squibb. The results were partly presented at the annual meeting of the German Society for Senology in Berlin 2001.

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Schmidt, M., Bachhuber, A., Victor, A. et al. p53 expression and resistance against paclitaxel in patients with metastatic breast cancer. J Cancer Res Clin Oncol 129, 295–302 (2003). https://doi.org/10.1007/s00432-003-0430-1

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  • DOI: https://doi.org/10.1007/s00432-003-0430-1

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