Decreased expression of BRCA2 mRNA predicts favorable response to docetaxel in breast cancer.
The clinical usefulness of BRCA1 and BRCA2 mRNA levels in tumor tissues in the prediction of response to docetaxel (DOC) treatment has been studied in breast-cancer patients. Twenty-five patients with locally advanced breast tumors (n = 13) or locally recurrent tumors (n = 12) underwent tumor biopsy and were treated with DOC (60 mg/m2 every 3 weeks). BRCA1 and BRCA2 mRNA levels in the tumors were determined by real-time PCR, and the expression of 6 biological markers (P-glycoprotein, p53, erbB2, BCL2, MIB1, estrogen receptor-alpha) in the tumors was determined by immunohistochemistry. BRCA2 mRNA levels (0.547 +/- 0.200, mean +/- SE) of responders to DOC treatment were significantly (p < 0.05) lower than those of non-responders (1.538 +/- 0.358), but there was no significant difference in BRCA1 mRNA levels between responders (0.389 +/- 0.081) and non-responders (0.779 +/- 0.172). Tumors were dichotomized into groups with high or low BRCA2 mRNA levels according to the cut-off value of 0.13. The response rate (25%) of tumors with high BRCA2 mRNA levels was significantly (p < 0.01) lower than that (100%) of tumors with low BRCA2 mRNA levels. Positive predictive value, negative predictive value and diagnostic accuracy of the BRCA2 mRNA assay in the prediction of response to DOC were 100%, 75% and 80%, respectively. No significant difference was found between responders and non-responders in the expression status of any of the other 6 biological markers. These results suggest that BRCA2 mRNA levels in tumor tissues might be clinically useful in the prediction of response to DOC treatment in breast-cancer patients.
Egawa
C
C
Department of Surgical Oncology, Osaka University Medical School, Osaka, Japan.
Miyoshi
Y
Y
Takamura
Y
Y
Taguchi
T
T
Tamaki
Y
Y
Noguchi
S
S
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism; D024682:BRCA2 Protein; D015415:Biomarkers; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D016009:Chi-Square Distribution; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012334:RNA, Neoplasm / Q000378:metabolism; D043823:Taxoids; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; D019313:BRCA1 Protein; D024682:BRCA2 Protein; D015415:Biomarkers; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D043823:Taxoids; D014157:Transcription Factors; D000077143:Docetaxel; D017239:Paclitaxel