title: Loss of BRCA1 expression may predict shorter time-to-progression in metastatic breast cancer patients treated with taxanes.
abstract: BACKGROUND
  Preclinical studies have indicated that BRCA1 functions differentially to modulate the chemosensitivity of cancer cells.
  
  
  METHODS
  To clarify these findings, BRCA1 expression in primary tumors was evaluated by immunohistochemistry in 50 patients with metastatic breast cancer.
  
  
  RESULTS
  BRCA1 expression was absent in 29 (58.0%) out of the 50 breast tumors tested. BRCA1-absent tumors were more frequently progesterone receptor-negative (p=0.019) than BRCA1-present tumors. Taxane-based chemotherapy was administered to 19 patients. Although BRCA1 expression did not relate to the clinical tumor response to taxane-based chemotherapy, time-to-progression (TTP) was significantly shorter in patients with BRCA1-absent tumors than in BRCA1-present tumors (mean+/-SD: 6.5 +/- 4.9 and 14.7 +/- 5.9 months, respectively; p=0.006). The Cox proportional hazard model revealed that BRCA1 absence was an independent predictor of progression (hazard ratio: 3.22; p=0.035).
  
  
  CONCLUSIONS
  These results suggest that the absence of BRCA1 expression is an independent predictor of shorter TTP in advanced breast cancer patients treated with taxane-based chemotherapy.
authors.affiliation: Department of Breast and Thyroid Surgery, Kawasaki Medical School, Okayama, Japan. kure@med.kawasaki-m.ac.jp
authors.forename: Junichi
authors.initials: J
authors.lastname: Kurebayashi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kurosumi
authors.forename: Sumiko
authors.initials: S
authors.lastname: Okubo
authors.forename: Tsunehisa
authors.initials: T
authors.lastname: Nomura
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Tanaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sonoo
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019313:BRCA1 Protein / Q000096:biosynthesis* / Q000172:deficiency; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004164:Diphosphonates / Q000008:administration & dosage; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use*; D000077268:Pamidronate; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use*; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D019313:BRCA1 Protein; D004164:Diphosphonates; D043823:Taxoids; D000077143:Docetaxel; D017258:Medroxyprogesterone Acetate; D000077268:Pamidronate; D000068878:Trastuzumab; D017239:Paclitaxel