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Table 3 Time- & ER-dependent effect assessment of individual gene signatures in predicting Distant Metastasis Free Survival (DMFS)

From: Systematic assessment of prognostic gene signatures for breast cancer shows distinct influence of time and ER status

      ER+ (n= 692)      ER– (n= 220)  
Gene signature PHaρ (p) Time n risk n event HR [95% CI] p PHaρ (p) n risk n event HR [95% CI] p
Intrinsic-RORs -0.23(0.0032)       -0.38(0.0069)     
   0-5 yr 692 126 1.46 [1.24-1.72] <0.0001   220 61 1.24 [0.94-1.63] 0.1230
   5-10 yr 566 41 0.83 [0.59-1.15] 0.2576   159 7 0.95 [0.49-1.85] 0.8892
   >10 yr 525 10 0.76 [0.36-1.60] 0.4650   152 5 0.49 [0.25-0.98] 0.0440
PAM50-RORs -0.27(0.0005)       -0.13(0.3676)     
   0-5 yr 692 126 2.16 [1.78-2.61] <0.0001   220 61 1.11 [0.86-1.44] 0.4312
   5-10 yr 566 41 1.26 [0.93-1.70] 0.1383   159 7 1.6 [0.64-4.03] 0.3161
   >10 yr 525 10 0.91 [0.48-1.73] 0.7773   152 5 0.54 [0.27-1.09] 0.0835
70-gene -0.18(0.0232)       -0.24(0.0702)     
   0-5 yr 692 126 1.70 [1.43-2.03] <0.0001   220 61 1.00 [0.79-1.28] 0.9739
   5-10 yr 566 41 1.16 [0.87-1.55] 0.3054   159 7 0.84 [0.43-1.65] 0.6189
   >10 yr 525 10 1.06 [0.57-1.96] 0.8468   152 5 0.40 [0.21-0.78] 0.0066
76-gene -0.20(0.0092)       -0.26(0.0565)     
   0-5 yr 692 126 1.83 [1.55-2.17] <0.0001   220 61 1.30 [1.04-1.62] 0.0228
   5-10 yr 566 41 1.32 [0.99-1.76] 0.0551   159 7 1.12 [0.51-2.48] 0.7745
   >10 yr 525 10 0.58 [0.28-1.20] 0.1446   152 5 0.38 [0.09-1.57] 0.1828
GGI -0.32(<0.0001)       -0.29(0.0296)     
   0-5 yr 692 126 2.11 [1.77-2.52] <0.0001   220 61 1.07 [0.82-1.38] 0.6288
   5-10 yr 566 41 1.23 [0.91-1.66] 0.1735   159 7 1.22 [0.55-2.71] 0.6170
   >10 yr 525 10 0.73 [0.37-1.44] 0.3592   152 5 0.39 [0.18-0.84] 0.0165
WR -0.28(0.0001)       -0.43(0.0002)     
   0-5 yr 692 126 2.07 [1.72-2.48] <0.0001   220 61 1.39 [1.05-1.85] 0.0214
   5-10 yr 566 41 1.16 [0.86-1.56] 0.3341   159 7 0.80 [0.39-1.63] 0.5334
   >10 yr 525 10 0.63 [0.33-1.20] 0.1612   152 5 0.30 [0.12-0.75] 0.0098
Hypoxia -0.02(0.7717)       -0.04(0.7132)     
   0-5 yr 692 126 1.06 [0.88-1.26] 0.5483   220 61 1.50 [1.20-1.89] <0.0001
   5-10 yr 566 41 0.93 [0.68-1.27] 0.6427   159 7 1.41 [0.70-2.83] 0.3389
   >10 yr 525 10 1.10 [0.57-2.10] 0.7773   152 5 0.48 [0.17-1.35] 0.1645
RS -0.25(0.0019)       -0.23(0.0628)     
   0-5 yr 692 126 1.79 [1.55-2.07] <0.0001   220 61 1.19 [0.92-1.53] 0.1919
   5-10 yr 566 41 1.06 [0.78-1.43] 0.7311   159 7 0.78 [0.39-1.58] 0.4902
   >10 yr 525 10 0.65 [0.26-1.61] 0.3535   152 5 0.57 [0.25-1.30] 0.1798
EP -0.27(0.0004)       -0.18(0.2457)     
   0-5 yr 692 126 1.97 [1.66-2.33] <0.0001   220 61 1.11 [0.86-1.45] 0.4199
   5-10 yr 566 41 1.13 [0.83-1.53] 0.4393   159 7 1.04 [0.50-2.15] 0.9198
   >10 yr 525 10 1.02 [0.55-1.91] 0.9462   152 5 0.51 [0.25-1.04] 0.0628
  1. a PH test for time trend: scaled Schoenfeld residuals were tested against transformed time (Kaplan-Meier estimates) for violation of proportional hazard assumption in a univariate Cox model for individual gene signatures. P values are shown.
  2. Analysis was carried out on ER + group and ER- group separately. Preliminary test for time trend was performed by checking proportional hazard assumption in a Cox model§ per signature fitted on all tumors with follow-up time and event status available (column “PH”: correlation and asscoaited p value are reported)). Main effect associated with a signature for DMFS prediction in a certain follow-up time interval was estimated by a Cox model within each ER stratification. The Hazard Ratio (HR) along with its 95% confidence interval and the p value from the Wald test are shown. Numbers of patients at risk (n risk ) were computed at time point 0, 5 and 10 year, respectively.