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Title: Hallmarks of aromatase inhibitor drug resistance revealed by epigenetic profiling in breast cancer
Authors: Jansen, Maurice P H M ×
Knijnenburg, Theo
Reijm, Esther A
Simon, Iris
Kerkhoven, Ron
Droog, Marjolein
Velds, Arno
Van Laere, Steven
Dirix, Luc
Alexi, Xanthippi
Foekens, John A
Wessels, Lodewyk
Linn, Sabine C
Berns, Els M J J
Zwart, Wilbert #
Issue Date: Nov-2013
Publisher: Waverly Press
Series Title: Cancer Research vol:73 issue:22 pages:6632-41
Article number: 10.1158/0008-5472.CAN-13-0704
Abstract: Aromatase inhibitors are the major first-line treatment of estrogen receptor-positive breast cancer, but resistance to treatment is common. To date, no biomarkers have been validated clinically to guide subsequent therapy in these patients. In this study, we mapped the genome-wide chromatin-binding profiles of estrogen receptor α (ERα), along with the epigenetic modifications H3K4me3 and H3K27me3, that are responsible for determining gene transcription (n = 12). Differential binding patterns of ERα, H3K4me3, and H3K27me3 were enriched between patients with good or poor outcomes after aromatase inhibition. ERα and H3K27me3 patterns were validated in an additional independent set of breast cancer cases (n = 10). We coupled these patterns to array-based proximal gene expression and progression-free survival data derived from a further independent cohort of 72 aromatase inhibitor-treated patients. Through this approach, we determined that the ERα and H3K27me3 profiles predicted the treatment outcomes for first-line aromatase inhibitors. In contrast, the H3K4me3 pattern identified was not similarly informative. The classification potential of these genes was only partially preserved in a cohort of 101 patients who received first-line tamoxifen treatment, suggesting some treatment selectivity in patient classification.
URI: 
ISSN: 0008-5472
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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