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

W R Miller, A Larionov, T J Anderson, D B Evans, J M Dixon

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)10-21
Number of pages12
JournalPharmacogenomics Journal
Volume12
Issue number1
DOIs
Publication statusPublished - Feb 2012

Keywords

  • Aromatase Inhibitors
  • Breast Neoplasms
  • Cluster Analysis
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Nitriles
  • Prospective Studies
  • Time Factors
  • Transcriptome
  • Treatment Outcome
  • Triazoles

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