TABLE 4.

Multi‐state model in all breast cancer patients and in patients diagnosed with a first primary ER‐positive breast cancer: hazard ratio for the comparison of CHEK2 c.1100delC carriers versus non‐carriers for each transition.

Analysis	Transition	Description	HR (95% CI)	p	Cases	Events
All BC patients	1	First primary BC → CBC	2.37 (1.82–3.08)	<0.001	82,701	1816
	2	First primary BC → BC death	1.30 (1.09–1.56)	0.003		7467
	3	First primary BC → death not due to BC	1.00 (0.75–1.34)	0.98		4247
	4	First primary BC → death of unknown cause	1.07 (0.76–1.49)	0.70		3548
	5	CBC → BC death	1.23 (0.72–2.10)	0.46	1816	281
	6	CBC → death not due to BC	0.60 (0.14–2.52)	0.49		124
	7	CBC → death of unknown cause	1.21 (0.41–3.53)	0.73		94
Patients diagnosed with primary ER‐positive BC	1	First primary BC → CBC	2.55 (1.87–3.48)	<0.001	55,175	1133
	2	First primary BC → BC death	1.38 (1.12–1.71)	0.003		4266
	3	First primary BC → death not due to BC	1.13 (0.81–1.56)	0.47		2817
	4	First primary BC → death of unknown cause	0.97 (0.63–1.48)	0.87		2090
	5	CBC → BC death	1.49 (0.79–2.81)	0.21	1133	167
	6	CBC → death not due to BC	0.89 (0.20–4.06)	0.89		80
	7	CBC → death of unknown cause	0.61 (0.14–2.79)	0.53		55

Note: The models included age at first primary BC diagnosis, nodal status, tumor size, grade, radiotherapy and systemic treatment given for the first primary BC as covariates. The model based on all BC patient included ER status of the first primary BC as additional covariate. Baseline hazards were allowed to vary across country and transition. All the estimates from the model are shown in Tables S13 and S14.

Abbreviations: BC, breast cancer; CBC, contralateral breast cancer; CI, confidence interval; ER, estrogen receptor; HR, hazard ratio.