BRCA1 is both a prognostic and predictive biomarker of response to chemotherapy in sporadic epithelial ovarian cancer

Gynecol Oncol. 2011 Dec;123(3):492-8. doi: 10.1016/j.ygyno.2011.08.017. Epub 2011 Sep 13.

Abstract

Objectives: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • BRCA1 Protein / biosynthesis
  • BRCA1 Protein / genetics*
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics*
  • Bridged-Ring Compounds / administration & dosage
  • Carcinoma, Ovarian Epithelial
  • Cohort Studies
  • Disease-Free Survival
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Multivariate Analysis
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Neoplasms, Glandular and Epithelial / genetics*
  • Neoplasms, Glandular and Epithelial / metabolism
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / therapeutic use*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Predictive Value of Tests
  • Retrospective Studies
  • Survival Rate
  • Taxoids / administration & dosage

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • Biomarkers, Tumor
  • Bridged-Ring Compounds
  • Organoplatinum Compounds
  • Taxoids
  • taxane