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

Zhao, Xi; Rødland, Einar Andreas; Sørlie, Therese; Vollan, Hans Kristian Moen; Russnes, Hege G; Kristensen, Vessela N; Lingjærde, Ole Christian; Børresen-Dale, Anne-Lise

doi:10.1186/1471-2407-14-211

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	PH^aρ (p)	Time	n_risk	n_event	HR [95% CI]	p	PH^aρ (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

^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.
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.

Back to article page