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High Thioredoxin Expression Is Associated with Resistance to Docetaxel in Primary Breast Cancer

Authors' Affiliations: ¹ Department of Breast and Endocrine Surgery, Graduate School of Medicine, Osaka University, Suita City, Osaka, Japan; ² Research Institute, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan; ³ Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital; and ⁴ Department of Biological Responses, Laboratory of Infection and Prevention, Institute for Virus Research, Kyoto University, Kyoto, Japan

Requests for reprints: Shinzaburo Noguchi, Department of Breast and Endocrine Surgery, Graduate School of Medicine, Osaka University, 2-2-E10 Yamadaoka, Suita City, Osaka 565-0871, Japan. Phone: 81-6-6879-3772; Fax: 81-6-6879-3779; E-mail: noguchi{at}onsurg.med.osaka-u.ac.jp.

Purpose: 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.

Patients and Methods: Sixty-three primary breast cancer patients were treated with docetaxel (60 mg/m², 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.

Conclusion: 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.

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