Added value of systemic inflammation markers for monitoring response to neoadjuvant chemotherapy in breast cancer patients

Table 1 Demographics and baseline characteristics of the breast cancer patients undergoing neoadjuvant chemotherapy

Variables	Dummy variables	Training cohort				Testing cohort
		Overall (n = 287)	Yes (n = 255)	No (n = 32)	P value	Overall (n = 200)	Yes (n = 176)	No (n = 24)	P value
Age [median (IQR)],yr		61.00 (55.00, 70.00)	61.00 (54.00, 70.00)	64.00 (58.75, 69.25)	0.11	61.00 (55.75, 70.25)	61.00 (55.00, 70.25)	64.00 (57.75, 70.25)	0.28
Menopausal (%)	Yes	35 (12.2)	30 (11.8)	5 (15.6)	0.73	28 (14.0)	24 (13.6)	4 (16.7)	0.93
	No	252 (87.8)	225 (88.2)	27 (84.4)		172 (86.0)	152 (86.4)	20 (83.3)
T stage (%)	T1-2	216 (75.3)	196 (76.9)	20 (62.5)	0.12	156 (78.0)	140 (79.5)	16 (66.7)	0.24
	T3-4	71 (24.7)	59 (23.1)	12 (37.5)		44 (22.0)	36 (20.5)	8 (33.3)
N stage (%)	N0-1	71 (24.7)	58 (22.7)	13 (40.6)	0.04	52 (26.0)	40 (22.7)	12 (50.0)	0.01
	N2-3	216 (75.3)	197 (77.3)	19 (59.4)		148 (74.0)	136 (77.3)	12 (50.0)
Grade (%)	I-II	195 (67.9)	175 (68.6)	20 (62.5)	0.61	134 (67.0)	118 (67.0)	16 (66.7)	0.11
	III	92 (32.1)	80 (31.4)	12 (37.5)		66 (33.0)	58 (33.0)	8 (33.3)
Histology (%)	IDC	111 (38.7)	106 (41.6)	5 (15.6)	0.02	80 (40.0)	77 (43.8)	3 (12.5)	0.03
	ILC	91 (31.7)	79 (31.0)	12 (37.5)		61 (30.5)	51 (29.0)	10 (41.7)
	IMC	48 (16.7)	41 (16.1)	7 (21.9)		36 (18.0)	29 (16.5)	7 (29.2)
	Others	37 (12.9)	29 (11.4)	8 (25.0)		23 (11.5)	19 (10.8)	4 (16.7)
Molecular subtyping (%)	HER2-LuB	108 (37.6)	100 (39.2)	8 (25.0)	< 0.01	76 (38.0)	71 (40.3)	5 (20.8)	0.01
	HER2+	71 (24.7)	66 (25.9)	5 (15.6)		53 (26.5)	50 (28.4)	3 (12.5)
	HER2+LuB	29 (10.1)	24 (9.4)	5 (15.6)		18 (9.0)	15 (8.5)	3 (12.5)
	LuA	54 (18.8)	41 (16.1)	13 (40.6)		37 (18.5)	25 (14.2)	12 (50.0)
	TN	25 (8.7)	24 (9.4)	1 (3.1)		16 (8.0)	15 (8.5)	1 (4.2)
BMI (%)	≤ 18	21 (7.3)	21 (8.2)	0 (0.0)	0.22	11 (5.5)	11 (6.2)	0 (0.0)	0.42
	≥ 27	36 (12.5)	31 (12.2)	5 (15.6)		27 (13.5)	23 (13.1)	4 (16.7)
	18 - 27	230 (80.1)	203 (79.6)	27 (84.4)		162 (81.0)	142 (80.7)	20 (83.3)
Smoking (%)	No	258 (89.9)	231 (90.6)	27 (84.4)	0.43	182 (91.0)	161 (91.5)	21 (87.5)	0.79
	Yes	29 (10.1)	24 (9.4)	5 (15.6)		18 (9.0)	15 (8.5)	3 (12.5)
ER (%)	Negative	103 (35.9)	91 (35.7)	12 (37.5)	0.99	73 (36.5)	66 (37.5)	7 (29.2)	0.56
	Positive	184 (64.1)	164 (64.3)	20 (62.5)		127 (63.5)	110 (62.5)	17 (70.8)
PR (%)	Negative	165 (57.5)	141 (55.3)	24 (75.0)	0.05	109 (54.5)	91 (51.7)	18 (75.0)	0.05
	Positive	122 (42.5)	114 (44.7)	8 (25.0)		91 (45.5)	85 (48.3)	6 (25.0)
HER2 (%)	Negative	157 (54.7)	140 (54.9)	17 (53.1)	0.99	110 (55.0)	96 (54.5)	14 (58.3)	0.89
	Positive	130 (45.3)	115 (45.1)	15 (46.9)		90 (45.0)	80 (45.5)	10 (41.7)
PLT [median (IQR)] × 109/L		200.00 (154.50, 268.50)	187.00 (152.50, 245.50)	388.00 (334.50, 454.00)	< 0.01	202.50 (158.75, 267.25)	190.50 (154.00, 246.50)	377.00 (332.50, 443.50)	< 0.01
Neutrophil [median (IQR)] × 109/L		4.35 (3.52, 5.13)	4.54 (3.76, 5.23)	3.09 (2.02, 3.39)	< 0.01	4.44 (3.50, 5.21)	4.60 (3.78, 5.27)	3.09 (2.02, 3.35)	< 0.01
MONO [median (IQR)] × 109/L		0.40 (0.25, 0.57)	0.38 (0.24, 0.50)	0.88 (0.80, 0.94)	< 0.01	0.41 (0.25, 0.58)	0.37 (0.23, 0.49)	0.86 (0.75, 0.91)	< 0.01
Lymphocyte [median (IQR)] × 109/L		3.09 (2.92, 3.30)	3.13 (2.96, 3.32)	1.64 (1.14, 2.16)	< 0.01	3.08 (2.92, 3.30)	3.12 (2.98, 3.32)	1.67 (1.14, 2.16)	< 0.01
NLR [median (IQR)]		1.43 (1.20, 1.67)	1.42 (1.20, 1.64)	1.56 (1.21, 2.68)	0.03	1.48 (1.20, 1.70)	1.47 (1.20, 1.67)	1.56 (1.22, 2.75)	< 0.01
LMR [median (IQR)]		7.62 (5.59, 12.96)	8.51 (6.18, 13.31)	1.86 (1.51, 2.47)	< 0.01	7.59 (5.60, 13.07)	8.53 (6.26, 13.46)	1.87 (1.59, 2.52)	< 0.01
PLR [median (IQR)]		64.45 (49.59, 85.43)	61.99 (47.81, 78.50)	237.76 (189.53, 342.96)	< 0.01	65.33 (50.30, 85.89)	62.36 (49.02, 78.10)	226.10 (189.53, 305.51)	< 0.01
ALB [median (IQR)],g/L		47.00 (39.00, 55.00)	48.00 (41.00, 56.00)	32.50 (27.50, 37.00)	< 0.01	47.00 (39.00, 55.25)	49.00 (41.00, 56.00)	31.50 (27.50, 37.00)	< 0.01
GLB [median (IQR)],g/L		23.00 (20.00, 26.00)	22.00 (20.00, 25.00)	35.00 (30.75, 41.00)	< 0.01	23.00 (20.00, 26.00)	23.00 (20.00, 25.00)	35.50 (30.75, 41.25)	< 0.01
A/G [median (IQR)]		2.11 (1.76, 2.53)	2.18 (1.88, 2.57)	0.88 (0.82, 1.03)	< 0.01	2.11 (1.71, 2.50)	2.18 (1.85, 2.55)	0.88 (0.82, 1.03)	< 0.01
LDL [median (IQR)],mmol/L		3.00 (2.88, 3.10)	2.97 (2.87, 3.08)	3.13 (3.05, 3.24)	< 0.01	3.00 (2.90, 3.08)	2.97 (2.88, 3.07)	3.13 (3.04, 3.22)	< 0.01
HDL [median (IQR)],mmol/L		1.26 (1.19, 1.33)	1.29 (1.20, 1.34)	1.17 (1.08, 1.20)	< 0.01	1.25 (1.18, 1.32)	1.28 (1.20, 1.33)	1.15 (1.08, 1.19)	0.02
TC [median (IQR)], mmol/L		0.52 (0.49, 0.56)	0.52 (0.48, 0.56)	0.56 (0.52, 0.58)	< 0.01	0.52 (0.48, 0.56)	0.52 (0.48, 0.56)	0.56 (0.52, 0.57)	< 0.01
TG [median (IQR)], mmol/L		1.82 (1.61, 2.15)	1.78 (1.59, 2.04)	2.34 (2.27, 2.39)	< 0.01	1.85 (1.60, 2.15)	1.79 (1.59, 2.04)	2.34 (2.27, 2.39)	< 0.01

rNACT: Response to neoadjuvant chemotherapy; Non-rNACT: None response to neoadjuvant chemotherapy; IQR: Interquartile range; ER: Estrogen receptor; PR: Progesterone receptor. HER2: Human epidermal growth factor receptor 2; IDC: Invasive ductal carcinoma; ILC: Invasive lobular carcinoma; IMC: Invasive mammary carcinoma; BMI: Body mass index; PLT: Platelet count; MONO: Monocyte count; NLR: Neutrophil-to-lymphocyte ratio; LMR: Lymphocyte-to-monocyte ratio; PLR: Platelet-to-lymphocyte ratio; ALB: Albumin; GLB: Globulin; A/G: Albumin-to-globulin ratio; LDL: Low density lipoprotein; HDL: High density lipoprotein; TC: Total cholesterol; TG: Triglyceride.

Table 2 Performance for response to neoadjuvant chemotherapy risk prediction of models in breast cancer patients

Model	AUC (95%CI)	Sensitivity	Specificity	PPV	NPV	Kappa	Brier
SVM	0.96 (0.91-1.01)	96.58	45.28	88.63	75.00	0.68	0.06
RF	0.94 (0.87-1.01)	94.44	68.75	86.67	68.75	0.65	0.07
NB	0.86 (0.79-0.93)	96.36	35.80	83.14	75.00	0.62	0.07
NN	0.88 (0.82-0.94)	93.15	25.00	93.15	53.15	0.62	0.07
DT	0.83 (0.77-0.89)	94.50	24.14	74.12	65.63	0.59	0.07
GLM	0.81 (0.71-0.91)	95.70	23.76	69.80	75.00	0.57	0.08

AUC: Area under the curve.area under the receiver operating characteristics curve; PPV: Positive predictive value; NPV: Negative predictive value, 95%CI: 95% confidence interval; SVM: Support vector machine; RF: Random forest; NB: Naive bayes ; NN: Neural network; DT: Decision tree; GLM: Generalized linear model.