A robust classifier of high predictive value to identify good prognosis patients in ER-negative breast cancer

Breast Cancer Res. 2008;10(4):R73. doi: 10.1186/bcr2138. Epub 2008 Aug 28.

Abstract

Introduction: Patients with primary operable oestrogen receptor (ER) negative (-) breast cancer account for about 30% of all cases and generally have a worse prognosis than ER-positive (+) patients. Nevertheless, a significant proportion of ER- cases have favourable outcomes and could potentially benefit from a less aggressive course of therapy. However, identification of such patients with a good prognosis remains difficult and at present is only possible through examining histopathological factors.

Methods: Building on a previously identified seven-gene prognostic immune response module for ER- breast cancer, we developed a novel statistical tool based on Mixture Discriminant Analysis in order to build a classifier that could accurately identify ER- patients with a good prognosis.

Results: We report the construction of a seven-gene expression classifier that accurately predicts, across a training cohort of 183 ER- tumours and six independent test cohorts (a total of 469 ER- tumours), ER- patients of good prognosis (in test sets, average predictive value = 94% [range 85 to 100%], average hazard ratio = 0.15 [range 0.07 to 0.36] p < 0.000001) independently of lymph node status and treatment.

Conclusions: This seven-gene classifier could be used in a polymerase chain reaction-based clinical assay to identify ER- patients with a good prognosis, who may therefore benefit from less aggressive treatment regimens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology*
  • Cohort Studies
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Models, Statistical
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Receptors, Estrogen / metabolism*
  • Regression Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Receptors, Estrogen