Table 2.

Distribution of events and multivariable analysis

	Sub–cohort (n = 679)			Additional cases (n = 303)	Case–cohort (n = 982)
	Patients	Events	Event rate per 100 patient-year (95% CI)		HR (95% CI)a	P-value
Ki-67 (30-9)b
< 14%	278	14	0.61 (0.35–1.00)	40	1.00
14–19%	171	20	1.47 (0.92–2.23)	74	1.88 (1.20–2.93)	0.006
≥ 20%	230	50	3.12 (2.34–4.08)	189	3.06 (1.93–4.84)	< 0.0001
Menopausal status
Pre/peri	289	34	1.50 (1.05–2.07)	145	1.00
Post	390	50	1.68 (1.26–2.20)	158	1.43 (0.82–2.49)	0.20
pT
pT1	466	34	0.88 (0.62–1.22)	124	1.00
pT2	191	44	3.51 (2.58–4.67)	152	1.75 (1.24–2.45)	0.001
pT3/4	22	6	4.41 (1.79–9.18)	27	3.26 (1.66–6.39)	0.0006
pN
pN0	378	18	0.57 (0.35–0.89)	81	1.00
pN+	402	64	3.22 (2.50–4.09)	121	1.86 (1.25–2.78)	0.002
Grade
G1	166	6	0.42 (0.17–0.87)	15	1.00
G2	343	36	1.36 (0.96–1.86)	146	1.90 (1.06–3.39)	0.03
G3	151	40	3.91 (2.83–5.28)	135	2.43 (1.27–4.65)	0.008
PVI
Absent	510	45	1.10 (0.81–1.46)	162	1.00
Present	169	39	3.36 (2.42–4.55)	141	1.53 (1.11–2.12)	0.009
ER
≥ 20%	665	81	1.57 (1.26–1.94)	300	1.00
< 20%	14	3	3.06 (0.78–8.33)	3	1.05 (0.43–2.61)	0.91
PgR
≥ 20%	474	53	1.45 (1.10–1.88)	199	1.00
< 20%	205	31	1.95 (1.35–2.73)	104	1.01 (0.72–1.41)	0.98
Adjuvant treatment
None	34	3	1.22 (0.31–3.33)	7	1.50 (0.61–3.69)	0.37
Hormone therapy	382	20	0.64 (0.39–0.94)	88	1.00
Chemotherapy	262	61	3.18 (2.45–4.06)	208	1.73 (1.11–2.69)	0.02

^aHazards ratio (HR and 95% confidence intervals (CI) obtained from Cox proportional Hazards regression with inverse subcohort sampling probability weighting as defined in Miettinen (1976) using the SAS macro CCREGRESSION provided by Kulathinal et al. (2007)

^bResults of an alternative multivariable model with Ki-67 (30-9) set as a continuous variable shows HR = 1.25 (95% CI 1.08–1.44; P = 0.002) for a 10% increase Ki-67, adjusted for menopausal status, pT, pN, grade, PVI, ER, PgR and adjuvant therapy