Journal
PHARMACOGENOMICS JOURNAL
Volume 12, Issue 1, Pages 10-21Publisher
SPRINGERNATURE
DOI: 10.1038/tpj.2010.67
Keywords
aromatase inhibitor; breast cancer; gene expression profiles; microarray analysis; neoadjuvant treatment
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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. The Pharmacogenomics Journal (2012) 12, 10-21; doi:10.1038/tpj.2010.67; published online 10 August 2010
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