title: High thioredoxin expression is associated with resistance to docetaxel in primary breast cancer.
abstract: 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.
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medicine, Osaka University, Suita City, Osaka, Japan.
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Miyoshi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Taguchi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tamaki
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakamura
authors.forename: Junji
authors.initials: J
authors.lastname: Yodoi
authors.forename: Kikuya
authors.initials: K
authors.lastname: Kato
authors.forename: Shinzaburo
authors.initials: S
authors.lastname: Noguchi
mesh_terms: 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
chemical_list: 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