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

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...

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Bibliographic Details
Published in:Journal of cancer research and clinical oncology 2003-05, Vol.129 (5), p.295-302
Main Authors: SCHMIDT, M, BACHHUBER, A, VICTOR, A, STEINER, E, MAHLKE, M, LEHR, H. A, PILCH, H, WEIKEL, W, KNAPSTEIN, P. G
Format: Article
Language:English
Subjects:
Adult
Antineoplastic Agents, Phytogenic - therapeutic use
ATP-Binding Cassette, Sub-Family B, Member 1 - analysis
Biological and medical sciences
Biomarkers, Tumor - analysis
Breast cancer
Breast Neoplasms - chemistry
Breast Neoplasms - drug therapy
Breast Neoplasms - pathology
Drug Resistance, Neoplasm
Drug therapy
Female
Gene Expression Regulation, Neoplastic - drug effects
Glutathione Transferase - analysis
Gynecology. Andrology. Obstetrics
Humans
Mammary gland diseases
Medical sciences
Middle Aged
Oncology
Paclitaxel - therapeutic use
Receptor, ErbB-2 - analysis
Tubulin - analysis
Tumor Suppressor Protein p53 - analysis
Tumor Suppressor Protein p53 - drug effects
Tumors
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Summary: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. 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. 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. The immunohistochemical detection of p53 characterizes patients with metastatic breast cancer unlikely to respond to paclitaxel.
ISSN:0171-5216
1432-1335
DOI:10.1007/s00432-003-0430-1