Purpose:Endocrine therapies include aromatase inhibitors and the selective oestrogen receptor (ER) down-regulator fulvestrant. This study aimed to determine if the reported efficacy of fulvestrant over anastrozole, and high- over low-dose fulvestrant, reflect distinct transcriptional responses. Experimental design:Global gene expression profiles from ERα-positive breast carcinomas before and during pre-surgical treatment with fulvestrant (n=22) or anastrozole (n=81), and corresponding in vitro models, were compared. Transcripts responding differently to fulvestrant and oestrogen (E) deprivation were integrated using gene ontology (GO), pathway and network analyses to evaluate their potential significance. Results:The overall transcriptional response to fulvestrant and E-deprivation was correlated (r=0.61 in pre-surgical studies, r=0.87 in vitro), involving down-regulation of E-regulated and proliferation-associated genes. The transcriptional response to fulvestrant was of greater magnitude than E-deprivation (slope=0.62 in pre-surgical studies, slope=0.63 in vitro). Comparative analyses identified 28 genes and 40 GO categories affected specifically by fulvestrant. Seventeen fulvestrant-specific genes, including CAV1/2, SNAI2 and NRP1, associated with ERα, androgen receptor (AR) and TP53, in networks regulating cell cycle, death, survival, and tumour morphology. Eighteen genes responding differently to fulvestrant specifically predicted anti-proliferative response to fulvestrant, but not anastrozole. Transcriptional effects of low-dose fulvestrant correlated with high-dose treatment, but were of lower magnitude (ratio=0.29). Conclusions:The transcriptional response to fulvestrant has much in common with E-deprivation, but is stronger with distinctions potentially attributable to arrest of E-independent ERα activity and involvement of AR signalling. Genes responding differently to fulvestrant may have predictive utility. These data are consistent with the clinical efficacy of fulvestrant versus anastrozole and higher dosing regimens.
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 April 2025.
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#67
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Altmetric has tracked 22,760,687 research outputs across all sources so far. This one has received more attention than most of these and is in the 70th percentile.
So far Altmetric has tracked 12,571 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.7. This one has gotten more attention than average, scoring higher than 51% of its peers.
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