The human invasion signature (HIS) is prognostic of clinical outcome in breast cancer patient cohorts. (A) Metastasis-free survival Kaplan-Meier analysis on cases identified as high and low risk by the HIS in the NKI295 cohort. Hazard ratio, 3.10; 95% CI, 1.98 to 4.84; P = 3.99e-07 (log-rank test). Also shown is the recurrence-free survival Kaplan-Meier analysis on cases identified as high and low risk by the HIS in the UNC232 cohort. Hazard ratio, 2.84; 95% CI, 1.60 to 5.00; P = 2.15e-05 (log-rank test). (B) One thousand signatures of equal size to the HIS were generated by picking random genes from the genome, and their association to distant metastasis in the NKI295 cohort was calculated. In the scatterplot shown here, each dot represents the P value calculated for each of the random signatures. Blue line, P value of 0.05; red line, P value cutoff for the best 5% random signatures (P = 2.41e-05); green line, P value for the HIS (P = 3.99e-07). (C) Multivariate Cox-Proportional Hazard Regression Analysis of the HIS in the NKI295 and UNC232 cohorts, incorporating established clinical parameters. HR, hazard ratio; CI, confidence interval.