Table 4. Hazard Ratios (HR) and 95% CI of all-cause and breast-cancer specific mortality in subgroups of HEAL participants.

Subgroup	IGF-1a			IGFBP-3b
	HR	95% CI	Pd	HR	95% CI	Pd
Breast-Cancer Specific Mortalityc
SEER Stage 2 (Local)	1.00 2.54	Ref 0.82-7.83	0.15	1.00 0.19	Ref 0.03-1.45	0.19
SEER Stage 3 (Regional)	1.00 4.57	Ref 1.48-14.03		1.00 0.83	Ref 0.26-2.59
ER Negativee	1.00 4.74	Ref 1.30-17.29	0.59	1.00 0.71	Ref 0.15-3.38	0.69
ER Positive	1.00 3.33	Ref 1.09-10.17		1.00 0.50	Ref 0.16-1.65
BMI ≤ 25	1.00 2.17	Ref 0.78-6.03	0.09	1.00 0.46	Ref 0.13-1.768	0.50
BMI >25	1.00 5.82	Ref 1.80-18.83		1.00 0.58	Ref 0.16-2.13
Tamoxifen at blood draw (No)	1.00 3.40	Ref 1.15-10.11	0.86	1.00 0.67	Ref 0.15-3.04	0.76
Tamoxifen at blood draw (Yes)f	1.00 4.01	Ref 1.12-14.43		1.00 0.41	Ref 0.12-1.38
All-cause Mortality
SEER Stage 2 (Local)	1.00 2.09	Ref 0.96-4.56	0.05	1.00 0.29	Ref 0.09-0.95	0.11
SEER Stage 3 (Regional)	1.00 4.88	Ref 2.01-11.88		1.00 0.87	Ref 0.32-2.31
ER Negativee	1.00 4.09	Ref 1.44-11.61	0.43	1.00 0.53	Ref 0.11-2.39	0.61
ER Positive	1.00 2.57	Ref 1.19-5.55		1.00 0.62	Ref 0.27-1.41
BMI ≤ 25	1.00 2.12	Ref 1.00-4.92	0.22	1.00 0.56	Ref 0.21-1.52	0.53
BMI >25	1.00 3.83	Ref 1.70-8.65		1.00 0.52	Ref 0.19-1.40
Tamoxifen at blood draw (No)f	1.00 2.39	Ref 1.12-5.07	0.31	1.00 0.78	Ref 0.29-2.09	0.29
Tamoxifen at blood draw (Yes)	1.00 5.17	Ref 2.03-13.17		1.00 0.33	Ref 0.11-10.93

^aIGF-1 comparing levels in the highest quintile to levels in all other quintiles combined

^bIGFBP-3 comparing levels in the highest quintile to levels in all other quintiles combined

^cFully adjusted model: IGF-1 and IGFBP-3, BMI (categorical <18.5; ≥ 18.5 and < 25; ≥ 25 and < 40; > 40 kg/m²); Race/ethnicity/site; tamoxifen use at time of blood draw (Yes/No); treatment received at diagnosis

^dTest for interaction

^e57 (8 deaths; 3 breast cancer deaths) were of unknown ER status

^f3 participants had unknown tamoxifen use at time of blood draw.