Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer.
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.
Buyse
Marc
M
International Drug Development Institute, Brussels, Belgium.
Loi
Sherene
S
van't Veer
Laura
L
Viale
Giuseppe
G
Delorenzi
Mauro
M
Glas
Annuska M
AM
d'Assignies
Mahasti Saghatchian
MS
Bergh
Jonas
J
Lidereau
Rosette
R
Ellis
Paul
P
Harris
Adrian
A
Bogaerts
Jan
J
Therasse
Patrick
P
Floore
Arno
A
Amakrane
Mohamed
M
Piette
Fanny
F
Rutgers
Emiel
E
Sotiriou
Christos
C
Cardoso
Fatima
F
Piccart
Martine J
MJ
D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D012372:ROC Curve; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D012680:Sensitivity and Specificity; D016019:Survival Analysis
D014408:Biomarkers, Tumor