Sequential changes in gene expression profiles in breast cancers during treatment with the aromatase inhibitor, letrozole.
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.
Miller
W R
WR
Edinburgh Breast Unit Research Group, Western General Hospital, Edinburgh, UK. w.r.miller@ed.ac.uk
Larionov
A
A
Anderson
T J
TJ
Evans
D B
DB
Dixon
J M
JM
D047072:Aromatase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000077289:Letrozole; D009570:Nitriles / Q000494:pharmacology / Q000627:therapeutic use*; D011446:Prospective Studies; D013997:Time Factors; D059467:Transcriptome; D016896:Treatment Outcome; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use*
D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole