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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Integrative analyses identify modulators of response to neoadjuvant aromatase inhibitors in patients with early breast cancer
|
|---|---|
| Published in |
Breast Cancer Research, March 2015
|
| DOI | 10.1186/s13058-015-0532-0 |
| Pubmed ID | |
| Authors |
Elena López-Knowles, Paul M Wilkerson, Ricardo Ribas, Helen Anderson, Alan Mackay, Zara Ghazoui, Aradhana Rani, Peter Osin, Ash Nerurkar, Lorna Renshaw, Alexey Larionov, William R Miller, J Michael Dixon, Jorge S Reis-Filho, Anita K Dunbier, Lesley-Ann Martin, Mitch Dowsett |
| Abstract |
Aromatase inhibitors (AIs) are a vital component of estrogen receptor positive (ER+) breast cancer treatment. De novo and acquired resistance, however, is common. The aims of this study were to relate patterns of copy number aberrations to molecular and proliferative response to AIs, to study differences in the patterns of copy number aberrations between breast cancer samples pre- and post-AI neoadjuvant therapy, and to identify putative biomarkers for resistance to neoadjuvant AI therapy using an integrative analysis approach. Samples from 84 patients derived from two neoadjuvant AI therapy trials were subjected to copy number profiling by microarray-based comparative genomic hybridisation (aCGH, n = 84), gene expression profiling (n = 47), matched pre- and post-AI aCGH (n = 19 pairs) and Ki67-based AI-response analysis (n = 39). Integrative analysis of these datasets identified a set of nine genes that, when amplified, were associated with a poor response to AIs, and were significantly overexpressed when amplified, including CHKA, LRP5 and SAPS3. Functional validation in vitro, using cell lines with and without amplification of these genes (SUM44, MDA-MB134-VI, T47D and MCF7) and a model of acquired AI-resistance (MCF7-LTED) identified CHKA as a gene that when amplified modulates estrogen receptor (ER)-driven proliferation, ER/estrogen response element (ERE) transactivation, expression of ER-regulated genes and phosphorylation of V-AKT murine thymoma viral oncogene homolog 1 (AKT1). These data provide a rationale for investigation of the role of CHKA in further models of de novo and acquired resistance to AIs, and provide proof of concept that integrative genomic analyses can identify biologically relevant modulators of AI response. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 1 | 50% |
| United Kingdom | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 50% |
| Science communicators (journalists, bloggers, editors) | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 3% |
| Unknown | 37 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 8 | 21% |
| Other | 4 | 11% |
| Student > Master | 4 | 11% |
| Student > Ph. D. Student | 3 | 8% |
| Professor > Associate Professor | 2 | 5% |
| Other | 4 | 11% |
| Unknown | 13 | 34% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 9 | 24% |
| Biochemistry, Genetics and Molecular Biology | 5 | 13% |
| Agricultural and Biological Sciences | 4 | 11% |
| Nursing and Health Professions | 3 | 8% |
| Business, Management and Accounting | 1 | 3% |
| Other | 4 | 11% |
| Unknown | 12 | 32% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. 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 18 March 2015.
All research outputs
#17,285,668
of 25,373,627 outputs
Outputs from Breast Cancer Research
#1,535
of 2,052 outputs
Outputs of similar age
#166,200
of 274,513 outputs
Outputs of similar age from Breast Cancer Research
#41
of 50 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,052 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.2. This one is in the 19th percentile – i.e., 19% of its peers scored the same or lower than it.
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