title: Decreased expression of BRCA2 mRNA predicts favorable response to docetaxel in breast cancer.
abstract: 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.
authors.affiliation: Department of Surgical Oncology, Osaka University Medical School, Osaka, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Egawa
authors.forename: Y
authors.initials: Y
authors.lastname: Miyoshi
authors.forename: Y
authors.initials: Y
authors.lastname: Takamura
authors.forename: T
authors.initials: T
authors.lastname: Taguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Tamaki
authors.forename: S
authors.initials: S
authors.lastname: Noguchi
mesh_terms: 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*
chemical_list: 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