CD163+ macrophages in the triple-negative breast tumor microenvironment are associated with improved survival in the Women’s Circle of Health Study and the Women’s Circle of Health Follow-Up Study

Table 4 Multivariable Cox regression models assessing associations between CD163⁺ cell density tertiles with overall survival and breast cancer-specific survival within subtype

Subtype, model		Overall survival			Breast cancer-specific survival
Luminal	Characteristic	Events/N	HR (95% CI)¹	p-value	Events/N	HR (95% CI)¹	p-value
Model 1	CD163
	T1	24/110	–		10/110	–
	T2	17/110	0.81 (0.43–1.51)	0.50	8/110	0.99 (0.39–2.52)	0.98
	T3	24/110	0.99 (0.56–1.76)	0.98	16/110	1.40 (0.63–3.13)	0.41
	Age	65/330	1.25 (1.10–1.42)	< 0.001	34/330	1.56 (1.26–1.92)	< 0.001
Model 2	CD163
	T1	23/109	–		10/110	–
	T2	15/108	0.54 (0.28–1.07)	0.076	8/109	0.99 (0.39–2.52)	0.98
	T3	24/110	0.83 (0.46–1.52)	0.55	16/110	1.27 (0.57–2.86)	0.56
	Age	62/327	1.28 (1.11–1.47)	< 0.001	34/329	1.55 (1.25–1.93)	< 0.001
	BMI	62/327	1.27 (1.07–1.51)	0.006	34/329	1.29 (1.03–1.61)	0.027
	Stage
	I	26/166	–
	II	17/127	0.58 (0.30–1.16)	0.12
	III/IV	19/34	3.44 (1.69–6.99)	< 0.001
	Tumor size (cm)	62/327	1.24 (1.08–1.42)	0.002

Subtype, model		Overall survival			Breast cancer-specific survival
HER2+	Characteristic	Events/N	HR (95% CI)¹	p-value	Events/N	HR (95% CI)¹	p-value
Model 1	CD163
	T1	6/31	–		4/31	–
	T2	6/31	0.99 (0.31–3.15)	0.99	2/31	0.42 (0.07–2.40)	0.33
	T3	8/30	1.37 (0.47–4.04)	0.57	3/30	0.54 (0.11–2.64)	0.45
	Age	20/92	1.26 (1.03–1.54)	0.024	9/92	1.78 (1.21–2.61)	0.003
Model 2	CD163
	T1	6/31	–
	T2	6/31	0.59 (0.16–2.16)	0.43
	T3	7/29	0.67 (0.19–2.31)	0.52
	Age	19/91	1.34 (1.09–1.66)	0.007
	Tumor size (cm)	19/91	1.70 (1.11–2.60)	0.015

Subtype, model		Overall survival			Breast cancer-specific survival
Triple negative	Characteristic	Events/N	HR (95% CI)¹	p-value	Events/N	HR (95% CI)¹	p-value
Model 1	CD163
	T1	20/40	–		9/40	–
	T2	12/40	0.59 (0.29–1.21)	0.15	5/40	0.61 (0.20–1.85)	0.38
	T3	8/40	0.36 (0.16–0.83)	0.017	3/40	0.36 (0.10–1.38)	0.14
	Age	40/120	1.07 (0.93–1.23)	0.34	17/120	1.26 (1.01–1.58)	0.041
Model 2	CD163+
	T1	18/38	–		9/40	–
	T2	11/38	0.44 (0.19–1.01)	0.052	5/40	0.70 (0.23–2.13)	0.53
	T3	8/40	0.30 (0.12–0.73)	0.008	3/40	0.38 (0.10–1.44)	0.15
	Age	37/116	1.28 (1.07–1.53)	0.008	17/120	1.38 (1.08–1.78)	0.012
	Stage
	I	5/34	–		3/35	–
	II	17/60	1.46 (0.46–4.64)	0.52	11/62	3.09 (0.82–11.7)	0.10
	III/IV	15/22	7.60 (2.01–28.7)	0.003	3/23	6.66 (1.23–36.2)	0.028
	Grade
	3	32/99	–
	1/2	5/17	0.33 (0.11–1.01)	0.053
	Node status
	Positive	23/47	–
	Negative	14/69	0.47 (0.20–1.13)	0.093

CD163⁺ cell density categorized into tertiles based on the distribution within subtype, separately
Model 1 adjusted for age across all subtypes and outcomes. Model 2 adjusted for parsimonious set of covariates found using covariate selection methods within subtype and outcome (Luminal/OS: age, BMI, stage, tumor size; Luminal/BCSS: age, BMI. HER2+ /OS: age, tumor size; HER2+ /BCSS: age. Triple Negative/OS: age, stage, grade, node status; Triple Negative/BCSS: age, stage)
Age, BMI, and tumor size modeled continuously reflecting a 5-year increase in age, a 5-kg/m² increase in BMI, and 1 cm increase in tumor size
¹HR Hazard Ratio, CI Confidence Interval

ISSN: 1465-542X