High thioredoxin expression is associated with resistance to docetaxel in primary breast cancer.
OBJECTIVE
Thioredoxin overexpression is suggested to be associated with resistance to several chemotherapeutic agents in vitro. In the present study, it has been studied whether or not high thioredoxin expression is associated with resistance to docetaxel therapy in breast cancer patients.


METHODS
Sixty-three primary breast cancer patients were treated with docetaxel (60 mg/m(2), q3w) for four cycles in the neoadjuvant setting. Expression of thioredoxin, estrogen receptor (ER), p53, BRCA-1, and Bcl-2 in tumor tissues obtained before docetaxel therapy was studied by immunohistochemistry (thioredoxin, p53, BRCA-1, and Bcl-2) and enzyme immunoassay (ER), and relationship of expression of these biomarkers with a pathologic response was investigated.


RESULTS
There was no significant correlation between the expression of p53, BRCA-1, or Bcl-2 and a response to docetaxel. However, tumors with high thioredoxin expression showed a significantly lower response rate (0%) than those with low thioredoxin expression (30.6%; P = 0.018) and ER-negative tumors showed a significantly higher response rate (32.4%) than ER-positive tumors (10.7%; P = 0.043). Thioredoxin expression significantly increased after docetaxel therapy (mean, 56.1%) as compared with that before docetaxel therapy (mean, 28.6%; P < 0.0001) but there was no significant association between the extent of increase in thioredoxin expression and response.


CONCLUSIONS
High thioredoxin expression in prechemotherapy tumor samples, but not the increase in thioredoxin expression induced by docetaxel, is associated with resistance to docetaxel in breast cancer. Thioredoxin and ER might be clinically useful in the prediction of a response to docetaxel.
Kim
Seung Jin
SJ
Department of Breast and Endocrine Surgery, Graduate School of Medicine, Osaka University, Suita City, Osaka, Japan.
Miyoshi
Yasuo
Y
Taguchi
Tetsuya
T
Tamaki
Yasuhiro
Y
Nakamura
Hajime
H
Yodoi
Junji
J
Kato
Kikuya
K
Noguchi
Shinzaburo
S
D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D043823:Taxoids / Q000627:therapeutic use*; D013879:Thioredoxins / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D019313:BRCA1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D043823:Taxoids; D016159:Tumor Suppressor Protein p53; D000077143:Docetaxel; D013879:Thioredoxins