| Title |
DNA repair signature is associated with anthracycline response in triple negative breast cancer patients
|
|---|---|
| Published in |
Breast Cancer Research and Treatment, June 2010
|
| DOI | 10.1007/s10549-010-0983-z |
| Pubmed ID | |
| Authors |
A. A. Rodriguez, A. Makris, M. F. Wu, M. Rimawi, A. Froehlich, B. Dave, S. G. Hilsenbeck, G. C. Chamness, M. T. Lewis, L. E. Dobrolecki, D. Jain, S. Sahoo, C. K. Osborne, J. C. Chang |
| Abstract |
We hypothesized that a subset of sporadic triple negative (TN) breast cancer patients whose tumors have defective DNA repair similar to BRCA1-associated tumors are more likely to exhibit up-regulation of DNA repair-related genes, anthracycline-sensitivity, and taxane-resistance. We derived a defective DNA repair gene expression signature of 334 genes by applying a previously published BRCA1-associated expression pattern to three datasets of sporadic TN breast cancers. We confirmed a subset of 69 of the most differentially expressed genes by quantitative RT-PCR, using a low density custom array (LDA). Next, we tested the association of this DNA repair microarray signature expression with pathologic response in neoadjuvant anthracycline trials of FEC (n = 50) and AC (n = 16), or taxane-based TET chemotherapy (n = 39). Finally, we collected paraffin-fixed, formalin-embedded biopsies from TN patients who had received neoadjuvant AC (n = 28), and tested the utility of the LDA to discriminate response. Correlation between RNA expression measured by the microarrays and 69-gene LDA was ascertained. This defective DNA repair microarray gene expression pattern was significantly associated with anthracycline response and taxane resistance, with the area under the ordinary receiver operating characteristic curve (AUC) of 0.61 (95% CI = 0.45-0.77), and 0.65 (95% CI = 0.46-0.85), respectively. From the FFPE samples, the 69-gene LDA could discriminate AC responders, with AUC of 0.79 (95% CI = 0.59-0.98). In conclusion, a promising defective DNA repair gene expression signature appears to differentiate TN breast cancers that are sensitive to anthracyclines and resistant to taxane-based chemotherapy, and should be tested in clinical trials with other DNA-damaging agents and PARP-1 inhibitors. |
Mendeley readers
The data shown below were compiled from readership statistics for 78 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 3% |
| Netherlands | 1 | 1% |
| Germany | 1 | 1% |
| Russia | 1 | 1% |
| Italy | 1 | 1% |
| Unknown | 72 | 92% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 24 | 31% |
| Other | 9 | 12% |
| Student > Ph. D. Student | 9 | 12% |
| Student > Master | 8 | 10% |
| Professor > Associate Professor | 6 | 8% |
| Other | 12 | 15% |
| Unknown | 10 | 13% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 25 | 32% |
| Medicine and Dentistry | 17 | 22% |
| Biochemistry, Genetics and Molecular Biology | 10 | 13% |
| Computer Science | 4 | 5% |
| Psychology | 3 | 4% |
| Other | 5 | 6% |
| Unknown | 14 | 18% |
Attention Score in Context
This research output has an Altmetric Attention Score of 6. 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 13 August 2019.
All research outputs
#4,712,503
of 22,856,968 outputs
Outputs from Breast Cancer Research and Treatment
#888
of 4,659 outputs
Outputs of similar age
#19,522
of 94,006 outputs
Outputs of similar age from Breast Cancer Research and Treatment
#7
of 38 outputs
Altmetric has tracked 22,856,968 research outputs across all sources so far. Compared to these this one has done well and is in the 76th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,659 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.2. This one has gotten more attention than average, scoring higher than 74% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 94,006 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 73% of its contemporaries.
We're also able to compare this research output to 38 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 65% of its contemporaries.