Estrogen independent gene expression defines clinically relevant subgroups of estrogen receptor positive breast cancer

BMC Cancer. 2014 Nov 24:14:871. doi: 10.1186/1471-2407-14-871.

Abstract

Background: Human breast cancer represents a significantly heterogeneous disease. Global gene expression profiling measurements have been used to classify tumors into multiple molecular subtypes. The capacity to define subtypes of breast tumors provides a framework to enable improved understanding of the mechanisms of breast oncogenesis, as well as to provide opportunities for improved therapeutic intervention in patients.

Methods: We used publicly available gene expression profiling data to identify 'estrogen independent' genes in estrogen receptor alpha (ER+) breast tumors, and subsequently identified 6 subgroups of ER+breast tumors.

Results: Each of the 6 identified subgroups exhibited distinct clinical behaviors and biology. Patients whose tumors comprised subgroups 2,5&6 experienced excellent long-term survival, whereas those patients whose tumors belonged to subgroups 1&4 experienced much poorer survival. Breast tumor cell lines representative of the different subgroups responded to therapeutic compounds in accordance with their subgroup classification.

Conclusions: These data support the existence of 6 distinct subgroups of ER+breast cancer and suggest that knowledge of the ER+subgroup status of patient samples have the potential to guide therapy choice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / classification*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Databases, Genetic
  • Drug Resistance, Neoplasm
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Receptors, Estrogen / biosynthesis*
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Receptors, Estrogen