Sequential changes in gene expression profiles in breast cancers during treatment with the aromatase inhibitor, letrozole

Pharmacogenomics J. 2012 Feb;12(1):10-21. doi: 10.1038/tpj.2010.67. Epub 2010 Aug 10.

Abstract

The study aim was to identify early (within 14 days) and late changes (by 3 months) in breast cancer gene expression profiles associated with neoadjuvant therapy with letrozole. RNA from sequential tumour biopsies in 54 patients was analyzed on microarrays; changes were determined by frequency, magnitude and significance analyses. Substantially more genes were changed at 3 months (1503) than at 14 days (237). Early changed genes were associated with cell cycle (downregulation), blood vessel development and extracellular matrix (upregulation); late changes included 'cellular metabolic process', 'generation of precursor metabolites and energy' (decreased) and 'cell adhesion' 'biological adhesion' (increased). A striking difference between the early and late changes was the general location of downregulated genes-nuclear structures at 14 days and mitochondria after 3 months. These changes in gene expression profiles provide a new and important database by which to understand molecular mechanisms of letrozole in breast cancers.

MeSH terms

  • Aromatase Inhibitors / pharmacology
  • Aromatase Inhibitors / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Cluster Analysis
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic* / drug effects
  • Humans
  • Letrozole
  • Nitriles / pharmacology
  • Nitriles / therapeutic use*
  • Prospective Studies
  • Time Factors
  • Transcriptome*
  • Treatment Outcome
  • Triazoles / pharmacology
  • Triazoles / therapeutic use*

Substances

  • Aromatase Inhibitors
  • Nitriles
  • Triazoles
  • Letrozole