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

The Pharmacogenomics Journal volume 12, pages 10–21 (2012)Cite this article

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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.

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Authors and Affiliations

  1. Edinburgh Breast Unit Research Group, Western General Hospital, Edinburgh, UK

    W R Miller, A Larionov, T J Anderson & J M Dixon

  2. Novartis Institutes for Biomedical Research Basel, Oncology Research, Basel, Switzerland

    D B Evans

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  1. W R Miller
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  2. A Larionov
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  3. T J Anderson
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  4. D B Evans
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  5. J M Dixon
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Correspondence to W R Miller.

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DBE is an employee and share holder of Novartis Pharma AG. Other authors declare no conflict of interest.

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Miller, W., Larionov, A., Anderson, T. et al. Sequential changes in gene expression profiles in breast cancers during treatment with the aromatase inhibitor, letrozole. Pharmacogenomics J 12, 10–21 (2012). https://doi.org/10.1038/tpj.2010.67

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