title: BRCA1 is both a prognostic and predictive biomarker of response to chemotherapy in sporadic epithelial ovarian cancer.
abstract: OBJECTIVE
  We investigated the relationship between BRCA1 protein expression by immunohistochemistry (IHC) and clinical outcome following platinum and platinum/taxane chemotherapy in sporadic epithelial ovarian cancer (EOC).
  
  
  METHODS
  BRCA1 IHC was performed on a cohort of 292 ovarian tumours from two UK oncology centres. BRCA1 protein expression levels were correlated with overall survival (OS), progression free survival (PFS) and clinical response to chemotherapy by multivariate analysis.
  
  
  RESULTS
  EOC patients with absent/low BRCA1 protein expression (41%) had a better chance of clinical response following chemotherapy as compared to patients with high BRCA1 expression (odds ratio 2.47: 95%CI 1.10-5.55, p=0.029). Patients with absent/low BRCA1 had a higher probability of clinical response following single agent platinum compared to high BRCA1 expressing patients (68.5% vs. 46.8%), while addition of a taxane increased response rates independent of BRCA1. Overall, patients with absent/low BRCA1 had a better clinical outcome compared to patients with high BRCA1 protein expression in terms of both OS (HR=0.65: 95%CI 0.48-0.88, p=0.006) and PFS (HR=0.74, 95%CI 0.55-0.98, p=0.040).
  
  
  CONCLUSIONS
  We confirm that absent/low BRCA1 protein expression is a favourable prognostic marker. However, we also provide the first evidence that absent/low BRCA1 protein expression in sporadic EOC patients predicts for an improved clinical response to chemotherapy.
authors.affiliation: Centre for Cancer Research and Cell Biology, Queens University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, N. Ireland, UK.
authors.forename: Judith E
authors.initials: JE
authors.lastname: Carser
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Quinn
authors.forename: Caroline O
authors.initials: CO
authors.lastname: Michie
authors.forename: Eamonn J
authors.initials: EJ
authors.lastname: O'Brien
authors.forename: W Glenn
authors.initials: WG
authors.lastname: McCluggage
authors.forename: Perry
authors.initials: P
authors.lastname: Maxwell
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lamers
authors.forename: Tong F
authors.initials: TF
authors.lastname: Lioe
authors.forename: Alistair R W
authors.initials: AR
authors.lastname: Williams
authors.forename: Richard D
authors.initials: RD
authors.lastname: Kennedy
authors.forename: Charlie
authors.initials: C
authors.lastname: Gourley
authors.forename: D Paul
authors.initials: DP
authors.lastname: Harkin
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000096:biosynthesis / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D000077216:Carcinoma, Ovarian Epithelial; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor; D001952:Bridged-Ring Compounds; D009944:Organoplatinum Compounds; D043823:Taxoids; C080625:taxane