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| Status |
Public on Aug 07, 2015 |
| Title |
Differences in the Transcriptional Response to Fulvestrant and Estrogen Deprivation in ER-Positive Breast Cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Aromatase inhibitors are first-line postmenopausal agents for estrogen receptor alpha (ERa)-positive breast cancer. However, there is considerable response heterogeneity and women frequently relapse. Estrogen deprivation does not completely arrest ERa activity, and transactivation of the unliganded receptor may continue through cross-talk with growth factor pathways. In contrast with aromatase inhibitors, the selective ER downregulator fulvestrant also abrogates ligand-independent ERa activity. The benefit of fulvestrant as an alternative, combination, or sequential therapy to aromatase inhibitor has been reported, but molecular mechanisms underpinning its relative efficacy remain unclear and biomarkers for patient selection are lacking. This study demonstrates, for the first time, that the overall transcriptional response to fulvestrant is of greater magnitude than estrogen deprivation, consistent with its clinical efficacy and more complete blockade of estrogenic signaling. Using a robust integrative approach, we identify a subset of genes differentially affected by fulvestrant that comprises distinct biologic networks, correlates with antiproliferative response, and has potential utility as predictive biomarkers for fulvestrant.
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| Overall design |
Global gene expression profiles from ERĪ±-positive breast carcinomas before and during presurgical treatment with fulvestrant (n = 38) or anastrozole (n = 81), and corresponding in vitro models, were compared. Transcripts responding differently to fulvestrant and estrogen deprivation were identified and integrated using Gene Ontology, pathway and network analyses to evaluate their potential significance.
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This represents the data for fulvestrant only
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| Contributor(s) |
Gao Q, Martin LA |
| Citation(s) |
24916694 |
| Submission date |
Aug 06, 2015 |
| Last update date |
Feb 18, 2019 |
| Contact name |
Alice Gao |
| E-mail(s) |
alice.gao@icr.ac.uk
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| Organization name |
The Institute of Cancer Research
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| Department |
Breast Cancer Now
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| Lab |
Molecular Cell Biology
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| Street address |
237 Fulham Road
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| City |
London |
| State/province |
London |
| ZIP/Postal code |
SW3 6JB |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL6884 |
Illumina HumanWG-6 v3.0 expression beadchip |
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| Samples (76)
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| Relations |
| BioProject |
PRJNA292089 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE71791_RAW.tar |
6.3 Mb |
(http)(custom) |
TAR |
| GSE71791_non-normalized.txt.gz |
30.9 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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