Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer.
By M. Buyse, S. Loi, L. V. van’t Veer, G. Viale, Mauro Delorenzi, A. Glas, M. S. D'assignies, J. Bergh, R. Lidereau, P. Ellis and 10 more. Journal of the National Cancer Institute, 2006
1,237 citations recorded by the source corpus.
BACKGROUND A 70-gene signature was previously shown to have prognostic value in patients with node-negative breast cancer. Our goal was to validate the signature in an independent group of patients. METHODS Patients (n = 307, with 137 events after a median follow-up of 13.6 years) from five European centers were divided into high- and low-risk groups based on the gene signature classification and on clinical risk classifications. Patients were assigned to the gene signature low-risk group if their 5-year distant metastasis-free survival probability as estimated by the gene signature was greater than 90%. Patients were assigned to the clinicopathologic low-risk group if their 10-year survival probability, as estimated by Adjuvant! software, was greater than 88% (for estrogen receptor [ER]-positive patients) or 92% (for ER-negative patients). Hazard ratios (HRs) were estimated to compare time to distant metastases, disease-free survival, and overall survival in high- versus low-risk groups. RESULTS The 70-gene signature outperformed the clinicopathologic risk assessment in predicting all endpoints. For time to distant metastases, the gene signature yielded HR = 2.32 (95% confidence interval [CI] = 1.35 to 4.00) without adjustment for clinical risk and hazard ratios ranging from 2.13 to 2.15 after adjustment for various estimates of clinical risk; clinicopathologic risk using Adjuvant! software yielded an unadjusted HR = 1.68 (95% CI = 0.92 to 3.07). For overall survival, the gene signature yielded an unadjusted HR = 2.79 (95% CI = 1.60 to 4.87) and adjusted hazard ratios ranging from 2.63 to 2.89; clinicopathologic risk yielded an unadjusted HR = 1.67 (95% CI = 0.93 to 2.98). For patients in the gene signature high-risk group, 10-year overall survival was 0.69 for patients in both the low- and high-clinical risk groups; for patients in the gene signature low-risk group, the 10-year survival rates were 0.88 and 0.89, respectively. CONCLUSIONS The 70-gene signature adds independent prognostic information to clinicopathologic risk assessment for patients with early breast cancer.
Subfields: Cancer Research, Genetics, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/d026cfd87c94aea0cabe2e187aa22412ef72dc0d
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Cancer Research
In Genetics
Citations in the corpus
- Google Goes Cancer: Improving Outcome Prediction for Cancer Patients by Network-Based Ranking of Marker Genes (2012, methodology): “In a validation study on an independent data set of 307 node-negative breast cancer patients [23], the 70-gene test was shown to have a sensitivity of 90% and a specificity of 42%.”
- Improved classification of breast cancer by analysis of genetic alterations and gene expression profiling (2011, neutral): “Currently, large clinical trials are being conducted in order to confirm the accuracy of the 70-gene and OncotypeDX signatures [49, 50] [51].”
- Why Most Discovered True Associations Are Inflated (2008, background): “648).(37) Prognostic ability is Submitted 17 March 2008; accepted 27 May 2008; posted 14 July.”
- A New Molecular Predictor of Distant Recurrence in ER-Positive, HER2-Negative Breast Cancer Adds Independent Information to Conventional Clinical Risk Factors (2011, methodology): “Patients were considered as having low clinical risk when the 10-year risk as calculated by Adjuvant!Online was below 9% (14).”