Prediction of response to docetaxel by CYP3A4 mRNA expression in breast cancer tissues.
We studied the relationship between response of breast cancer to docetaxel (DOC) or cylophosphamide + epirubucin (CE) treatment and CYP3A4 mRNA expression in breast tumors. CYP3A4 inactivates DOC but not E, which is a predominant effector in CE treatment. Twenty patients with locally advanced breast tumors and 18 patients with locally recurrent tumors underwent tumor biopsy before chemotherapy, and CYP3A4 mRNA expression levels in tumor tissues were assayed by real-time quantitative polymerase chain reaction. Twenty-three patients were treated with DOC (60 mg/m(2) q3w) and 15 patients were treated with CE (C 600 mg/m(2) and E 60 mg/m(2) q3w). Patients with low CYP3A4 mRNA levels (n = 14) exhibited a significantly (p < 0.01) higher response rate (71%) to DOC treatment than those (n = 9) with high CYP3A4 mRNA levels (response rate, 11%). Positive predictive value, negative predictive value and diagnostic accuracy of CYP3A4 mRNA levels in the prediction of response to DOC were 71, 89, and 78%, respectively. However, no significant association was observed between CYP3A4 mRNA expression and response to CE treatment. These results suggest that intratumoral CYP3A4 mRNA levels might be useful as a predictor of response to DOC treatment, but not to CE treatment, in breast cancer patients. The increased inactivation of DOC by CYP3A4 in tumor tissues may play some role in the acquisition of resistance to DOC.
Miyoshi
Yasuo
Y
Department of Surgical Oncology, Osaka University Medical School, Osaka, Japan.
Ando
Akiko
A
Takamura
Yuuki
Y
Taguchi
Tetsuya
T
Tamaki
Yasuhiro
Y
Noguchi
Shinzaburo
S
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043823:Taxoids
D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen; D043823:Taxoids; D000077143:Docetaxel; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D017239:Paclitaxel