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


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.


CONCLUSIONS
The immunohistochemical detection of p53 characterizes patients with metastatic breast cancer unlikely to respond to paclitaxel.
Schmidt
M
M
Department of Obstetrics and Gynaecology, University Hospital Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany. MarcusSchmidtMD@aol.com
Bachhuber
A
A
Victor
A
A
Steiner
E
E
Mahlke
M
M
Lehr
H A
HA
Pilch
H
H
Weikel
W
W
Knapstein
P G
PG
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis; D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005982:Glutathione Transferase / Q000032:analysis; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D014404:Tubulin / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000187:drug effects
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D005982:Glutathione Transferase; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D014404:Tubulin; D016159:Tumor Suppressor Protein p53