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| Status |
Public on Nov 28, 2008 |
| Title |
A predictive and prognostic 38-gene expression signature for metastatic relapse in breast cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Background
Currently, no gene-expression signature (GES) established from node-positive cohorts, able to predict breast cancer evolution after systemic adjuvant chemotherapy, exists.
Methods
Gene-expression profiles of 252 node-positive patients (median follow-up: 7.7 years), mostly included in a randomized clinical trial (PACS01), receiving systemic adjuvant regimen, were determined by means of cDNA custom array representing 5,776 distinct genes.
Findings
In the training cohort, we established a 38-GES for the purpose of predicting time to distant metastasis. The 38-GES yielded unadjusted hazard ratio of 4.86 (95% CI=2.76-8.56). Even when adjusted with the two best clinicopathological prognostic scoring: NPI and Adjuvant!, 38-GES HR were 3.30 (1.81-5.99) and 3.40 (1.85-6.24), respectively. Furthermore, 38-GES improved mostly NPI and Adjuvant! intermediate-risk classified patients. NPI intermediate-risk patients (7-year MFS=87.2%) were divided into 2/3 (7-year MFS=95.5%) close to NPI low-risk group and 1/3 (7-year MFS=69.3%) close to NPI high-risk group (HR=6.97 [2.51-19.36]). Adjuvant! intermediate-risk patients (7-year MFS=88.0%) were divided into 2/3 (7-year MFS=94.8%) close to Adjuvant! low-risk group and 1/3 (7-year MFS=71.7%) close to Adjuvant! high-risk group (HR=5.31 [5.38-11.87]). The 38-GES was validated on gene-expression datasets from three external node-positive breast cancer subcohorts (n=224) generated from different microarray platforms. The 38-GES yielded unadjusted HR=2.95 (1.74-5.01). Furthermore, 38-GES showed performance in supplementary cohorts with different lymph-node status and endpoint (1,031 new patients).
Interpretation
The 38-GES represents a robust tool able to type systemic adjuvant treated node-positive patients at high risk of metastatic relapse, and especially powerful to separate NPI or Adjuvant! intermediate-risk node-positive patients.
Keywords: disease-state analysis
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| Overall design |
252 breast cancer patients at diagnosis examined with spotted cDNA nylon membrane.
Patient details:
PACS01x are 2 parts of a clinical trial :
PACS01A : patients had received 6 cycles of FEC100
PACS01B : patients had received 3 cycles of FEC100 then 3 cycles of Docetaxel
CCRG are patients from our local cancer center (Cancer Center René Gauducheau) included with the same criteria as PACS01A (6 cycles of FEC100).
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| Contributor(s) |
Jézéquel P, Campone M, Roché H, Gouraud W, Charbonnel C, Ricolleau G, Magrangeas F, Minvielle S, Genève J, Martin A, Bataille R, Campion L |
| Citation(s) |
19020972, 19513072 |
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| Submission date |
Apr 25, 2008 |
| Last update date |
Nov 08, 2019 |
| Contact name |
Wilfried Gouraud |
| Organization name |
ICO - UMGC
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| Department |
Integrated Center of Oncology René Gauducheau
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| Lab |
Omics Data Science Unit
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| Street address |
bd Jacques Monod
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| City |
Saint Herblain |
| ZIP/Postal code |
44805 |
| Country |
France |
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| Platforms (1) |
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| Samples (252)
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| Relations |
| BioProject |
PRJNA106779 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE11264_ALL_Patient_rawdata.txt |
38.9 Mb |
(ftp)(http) |
TXT |
| GSE11264_ALL_Testing_Probe_rawdata.txt |
40.3 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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