title: Prediction of response to docetaxel by immunohistochemical analysis of CYP3A4 expression in human breast cancers.
abstract: BACKGROUND
  Docetaxel (DOC) is inactivated by CYP3A4, high expression of which in tumor tissue might serve as a resistance mechanism. In the present study, the CYP3A4 protein level in breast cancers was determined by immunohistochemistry, and its relationship with the response to DOC treatment was studied.
  
  
  METHODS
  Thirty-one patients with locally advanced (n = 21) or recurrent (n = 10) breast cancers underwent tumor biopsy, followed by DOC treatment (60 mg/m2 q3w). Expression of CYP3A4 was studied by immunohistochemistry.
  
  
  RESULTS
  Patients with CYP3A4 negative tumors (n = 15) by immunohistochemistry showed a significantly (P < 0.01) higher response rate (67%) to DOC treatment than those with CYP3A4 positive tumors (n = 16, 19%). The positive predictive value, negative predictive value, and diagnostic accuracy of CYP3A4 expression by immunohistochemistry in the prediction of response to DOC were 67%, 81%, and 74%, respectively.
  
  
  CONCLUSIONS
  Immunohistochemical analysis of CYP3A4 expression in tumor cells might be clinically useful in the prediction of tumor response to DOC.
authors.affiliation: Department of Surgical Oncology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Miyoshi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Taguchi
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tamaki
authors.forename: Shinzaburo
authors.initials: S
authors.lastname: Noguchi
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D000077143:Docetaxel; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D011237:Predictive Value of Tests; D043823:Taxoids / Q000627:therapeutic use*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human