title: Increased expression of BRCA1 mRNA predicts favorable response to anthracycline-containing chemotherapy in breast cancers.
abstract: Clinical significance of BRCA1 and BRCA2 mRNA levels in tumor tissues as predictors of response to anthracycline-containing chemotherapy was studied in breast cancer patients. Fifty-one patients with locally advanced breast tumors (n = 43) or locally recurrent tumors (n = 8) underwent tumor biopsy and were treated with CE (cyclophosphamide (600 mg/m2) plus epirubicin (60 mg/m2), q3w). BRCA1 and BRCA2 mRNA levels in the tumors were determined by a real-time PCR assay, and the expression of p53 and erbB2 in tumors was determined by immunohistochemistry. BRCA1 mRNA levels (1.317 +/- 0.277, mean +/- S.E.) of responders were significantly (p < 0.05) higher than those (0.609 +/- 0.097) of non-responders but there was no significant difference in BRCA2 mRNA levels between responders (1.590 +/- 0.326) and non-responders (1.586 +/- 0.410). Tumors were dichotomized into the BRCA1 mRNA levels high and low group according to the cut-off value of 0.55. Response rate (65%) of tumors with high BRCA1 mRNA levels was significantly (p < 0.05) higher than that (32%) of tumors with low BRCA1 mRNA levels. There was no significant association between response to CE and the expression of p53 or erbB2. Positive predictive value, negative predictive value, and diagnostic accuracy of BRCA1 mRNA determination in the prediction of response to CE were 65, 68, and 67%, respectively. These results suggest a possibility that BRCA1 mRNA levels in tumor tissues might be useful in the prediction of response to CE treatment in breast cancer patients.
authors.affiliation: Department of Surgical Oncology, Osaka University Medical School, Suita, Osaka, Japan.
authors.forename: Chiyomi
authors.initials: C
authors.lastname: Egawa
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Motomura
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Miyoshi
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Takamura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Taguchi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tamaki
authors.forename: Hideo
authors.initials: H
authors.lastname: Inaji
authors.forename: Hiroki
authors.initials: H
authors.lastname: Koyama
authors.forename: Shinzaburo
authors.initials: S
authors.lastname: Noguchi
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics*; D003520:Cyclophosphamide / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D015870:Gene Expression / Q000235:genetics; D019398:Genes, BRCA1 / Q000502:physiology*; D024522:Genes, BRCA2 / Q000502:physiology*; D006801:Humans; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011237:Predictive Value of Tests
chemical_list: D000903:Antibiotics, Antineoplastic; D015251:Epirubicin; D003520:Cyclophosphamide