Table 2. Cox model incorporating time-dependent effects of prognostic variables.

	HR	B 1	95% CI	P-value	T	B 2	95% CI	P-value
Univariate analysis
Size (n=9793)	2.74	1.01	2.39–3.14	<0.001	0.79	−0.24	0.72–0.86	<0.001
Grade (n=10 066)	5.30	1.67	4.40–6.40	<0.001	0.53	−0.63	0.47–0.59	<0.001
Nodal status (n=9428)	4.02	1.39	3.30–4.90	<0.001	0.76	−0.27	0.67–0.87	<0.001
ER (n=10 592)	0.17	−1.77	0.14–0.20	<0.001	2.49	0.91	2.24–2.76	<0.001
PR (n=8802)	0.15	−1.90	0.13–0.19	<0.001	2.45	0.90	2.19–2.75	<0.001
HER2 (n=8100)	2.85	1.05	2.34–3.48	<0.001	0.70	−0.36	0.61–0.80	<0.001
BCL2 (n=7803)	0.21	−1.56	0.17–0.25	<0.001	2.02	0.70	1.78–2.31	<0.001
Multivariate analysis: Model 1 (n=6738)
ER	0.39	−0.94	0.29–0.51	<0.001	1.99	0.69	1.65–2.41	<0.001
PR	0.30	−1.20	0.23–0.40	<0.001	1.76	0.57	1.49–2.08	<0.001
HER2	1.50	0.41	1.20–1.89	<0.001	0.97	−0.03	0.82–1.14	0.69
BCL2	0.62	−0.48	0.48–0.80	<0.001	1.09	0.09	0.92–1.29	0.32
Multivariate analysis: Model 2 (n=5445)
Size	1.50	0.41	1.37–1.64	<0.001	NA
Grade	2.89	1.06	2.18–3.80	<0.001	0.67	−0.40	0.57–0.79	<0.001
Nodal status	3.21	1.17	2.50–4.12	<0.001	0.80	−0.22	0.68–0.94	0.006
ER	0.41	−0.89	0.30–0.54	<0.001	2.07	0.73	1.70–2.50	<0.001
PR	0.33	−1.11	0.24–0.46	<0.001	1.69	0.52	1.41–2.03	<0.001
HER2	1.31	0.27	1.15–1.50	<0.001	NA
BCL2	0.76	−0.25	0.66–0.88	<0.001	NA

Abbreviations: B₁=log(hazard ratio); B₂=log(time effect); BCL2=B-cell lymphoma 2; CI=confidence interval; ER=oestrogen receptor; HER2=human epidermal growth factor receptor 2; HR=hazard ratio (mortality); NA=not applicable; PR=progesterone receptor; T=time effect.

B₂ is positive when the HR increases with time and negative when the HR decreases with time.

Tumour size and grade were treated as continuous variables in the univariate and multivariate analyses.