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

J Cancer Res Clin Oncol. 2003 May;129(5):295-302. doi: 10.1007/s00432-003-0430-1. Epub 2003 Apr 25.

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/m(2 )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-pi, and beta-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-pi, and beta-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.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / analysis
  • Adult
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Drug Resistance, Neoplasm*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glutathione Transferase / analysis
  • Humans
  • Middle Aged
  • Paclitaxel / therapeutic use*
  • Receptor, ErbB-2 / analysis
  • Tubulin / analysis
  • Tumor Suppressor Protein p53 / analysis*
  • Tumor Suppressor Protein p53 / drug effects

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents, Phytogenic
  • Biomarkers, Tumor
  • Tubulin
  • Tumor Suppressor Protein p53
  • Glutathione Transferase
  • Receptor, ErbB-2
  • Paclitaxel