Predictive Value of Pretreatment Peripheral Neutrophil-to-Lymphocyte Ratio for Response to Neoadjuvant Chemotherapy and Breast Cancer Prognosis

Figures & data

Figure 1 Receiver operating curve for response to neoadjuvant chemotherapy was plotted to determine the optimum cut-off for neutrophil-to-lymphocyte ratio (NLR).

Table 1 Correlation Between Clinicopathological Parameters and NLR

Parameters	NLR		P value
	High (>1.8)	Low (≤1.8)
Age (n=282)			0.753
≤40	51 (73.9%)	18 (26.1%)
41–50	84 (76.4%)	26 (23.6%)
>50	74 (71.8%)	29 (28.2%)
Tumor stage (n=269)			0.486
cT1	34 (75.6%)	11 (24.4%)
cT2	101 (71.6%)	40 (28.4%)
cT3	35 (81.4%)	8 (18.6%)
cT4	27 (67.5%)	13 (32.5%)
Nodal status (n=267)			0.709
cN0	29 (78.4%)	8 (21.6%)
cN1	74 (72.5%)	28 (27.5%)
cN2	36 (70.6%)	15 (29.4%)
cN3	60 (77.9%)	17 (22.1%)
Clinical stage (n=274)			0.775
I–II	79 (73.1%)	29 (26.9%)
III	124 (74.7%)	42 (25.3%)
Molecular subtype (n=254)			0.154
Luminal A and B BC	127 (69.8%)	55 (30.2%)
HER2+BC	25 (75.8%)	8 (24.2%)
TNBC	33 (84.6%)	6 (15.4%)
Response to NAC (n=282)			0.045
pCR	34 (63.0%)	20 (37.0%)
Non-pCR	174 (76.3%)	54 (23.7%)
Cancer recurrence (n=282)			0.257
Yes	56 (78.9%)	15 (21.1%)
No	152 (72.0%)	59 (28.0%)
Death (n=282)			0.033
Yes	35 (87.5%)	5 (12.5%)
No	173 (71.5%)	69 (28.5%)

Abbreviations: NLR, neutrophil-to-lymphocyte ratio; cT and cN, clinical stages before neoadjuvant chemotherapy (NAC); luminal A, BC hormone-receptor positive (ER and/or PR positive), HER2 negative, and Ki-67 low; luminal B, BC hormone-receptor positive (ER and/or PR positive), and either HER2 positive or HER2 negative with high levels of Ki-67; HER2+BC, hormone-receptor negative (ER and PR negative) and HER2 positive; TNBC, triple-negative breast cancer; pCR, pathological complete response.

Figure 2 The response to neoadjuvant chemotherapy in neutrophil-to-lymphocyte ratio (NLR) high and low groups.

Table 2 Correlation Between NLR and LNR in Various Subtypes

Molecular Subtype	NLR	LNR		P value
		≤0.5	>0.5
Total	>1.8	155(82.4%)	33(17.6%)	0.531
	≤1.8	60(85.7%)	10(14.3%)
LA+LB	>1.8	85(76.6%)	26(23.4%)	0.041
	≤1.8	46(90.2%)	5(9.8%)
HER2-enriched	>1.8	22(88.0%)	3(12.0%)	0.137
	≤1.8	5(62.5%)	3(37.5%)
TNBC	>1.8	27(90.0%)	3(10.0%)	0.535
	≤1.8	5(83.3%)	1(16.7%)

Abbreviations: NLR, neutrophil-to-lymphocyte ratio; LNR, positive lymph node ratio; luminal A, BC hormone-receptor positive (ER and/or PR positive), HER2 negative, and Ki-67 low; luminal B, BC hormone-receptor positive (ER and/or PR positive), and either HER2 positive or HER2 negative with high levels of Ki-67; HER2-enriched, hormone-receptor negative (ER and PR negative) and HER2 positive; TNBC, triple-negative breast cancer.

Figure 3 The prognostic value of NLR for overall survival (A) and disease-free survival (B).

Figure 4 Kaplan–Meier analysis of overall survival and disease-free survival of patients undergoing axillary lymph node dissection in (A and B) positive lymph node ratio categories (LNRC) and (C and D) single LNR value (0.5).

Table 3 Univariate Analysis of Factors Affecting Overall Survival and Disease-Free Survival

Parameters	Univariate Analysis
	OS		DFS
	HR(95% CI)	P	HR(95% CI)	P
Age
≤40	1	0.293	1	0.729
41–50	2.027(0.743–5.535)	0.168	1.124(0.607–2.082)	0.710
>50	2.194(0.803–5.993)	0.125	1.272(0.693–2.335)	0.437
Tumor stage
cT1	1	0.042	1	0.083
cT2	1.091(0.396–3.007)	0.866	1.479(0.712–3.074)	0.294
cT3	2.467(0.804–7.572)	0.115	2.473(1.068–5.724)	0.035
cT4	2.994(0.997–8.985)	0.051	2.396(1.021–5.620)	0.045
Nodal status
cN0	1	0.324	1	0.046
cN1	2.487(0.556–11.125)	0.233	1.572(0.632–3.912)	0.331
cN2	3.637(0.771–17.157)	0.103	2.359(0.911–6.109)	0.077
cN3	3.545(0.799–15.720)	0.096	2.878(1.190–6.960)	0.019
Clinical stage
I	1	0.024	1	0.021
II	11,661.315(0–3.984E+85)	0.922	2.037(0.474–8.755)	0.339
III	39,441.586(0–1.346E+86)	0.912	3.735(0.908–15.360)	0.068
ER
Positive versus negative	1.218(0.619–2.396)	0.568	0.984(0.599–1.616)	0.949
PR
Positive versus negative	1.529(0.785–2.975)	0.212	1.246(0.777–1.998)	0.361
HER2
Positive versus negative	1.561(0.673–3.620)	0.299	0.837(0.486–1.440)	0.520
Molecular subtype
Luminal A and B BC	1	0.815	1	0.902
HER2+BC	1.282(0.487–3.375)	0.615	1.179(0.578–2.407)	0.650
TNBC	1.249(0.507–3.075)	0.629	1.022(0.516–2.024)	0.950
Response to NAC (pCR)
Yes versus no	2.805(0.861–9.135)	0.087	1.443(0.760–2.741)	0.262
Cancer recurrence
Yes versus no	20.504(8.515–49.370)	< 0.001	–	–
LNR(I)
≤0.5 versus >0.5	4.807(2.370–9.750)	< 0.001	4.730(2.826–7.917)	< 0.001
LNR(II)
LNR:0–0.2	1	< 0.001	1	< 0.001
0.2<LNR≤0.65	6.117(2.491–15.019)	< 0.001	4.216(2.374–7.489)	< 0.001
LNR>0.65	13.598(5.529–33.445)	< 0.001	8.385(4.510–15.590)	< 0.001
NLR
High versus low	2.940(1.041–8.298)	0.042	1.206(0.701–2.075)	0.500

Abbreviations: OS, overall survival; DFS, disease-free survival; cT and cN, clinical stages before neoadjuvant chemotherapy (NAC); luminal A, BC hormone-receptor positive (ER and/or PR positive), HER2 negative, and Ki-67 low; luminal B, BC hormone-receptor positive (ER and/or PR positive), and either HER2 positive or HER2 negative with high levels of Ki-67; HER2+, BC hormone-receptor negative (ER and PR negative) and HER2 positive; TNBC, triple-negative breast cancer; pCR, pathological complete response; LNR, positive lymph node ratio; NLR, neutrophil-to-lymphocyte ratio.

Table 4 Multivariate Analysis of Factors Affecting Overall Survival and Disease-Free Survival

Parameters	Multivariate Analysis
	OS		DFS
	HR(95% CI)	P	HR(95% CI)	P
Age
≤40	1	0.198	1	0.259
41–50	1.648(0.33–8.242)	0.543	0.784(0.365–1.685)	0.533
>50	3.167(0.652–15.371)	0.153	1.393(0.654–2.968)	0.391
Tumor stage
cT1	1	0.881	1	0.090
cT2	0.804(0.194–3.334)	0.764	1.901(0.671–5.389)	0.227
cT3	0.61(0.099–3.762)	0.595	4.433(1.267–15.507)	0.020
cT4	0.958(0.145–6.319)	0.964	2.199(0.594–8.144)	0.238
Nodal status
cN0	1	0.082	1	0.939
cN1	0.688(0.103–4.585)	0.699	0.766(0.236–2.485)	0.658
cN2	0.231(0.025–2.103)	0.193	0.593(0.111–3.172)	0.541
cN3	0.124(0.012–1.23)	0.075	0.686(0.138–3.399)	0.644
Clinical stage
I	1	0.203	1	0.839
II	4139.302(0–3.097E+77)	0.924	0.651(0.089–4.773)	0.673
III	19,822.98(0–1.50E+78)	0.909	0.497(0.047–5.305)	0.563
Response to NAC (pCR)
No versus yes	1.227(0.245–6.137)	0.803	–	–
Cancer recurrence
No versus yes	17.915(6.042–53.120)	< 0.001	–	–
LNR(I)
≤0.5 versus >0.5	0.264(0.027–2.553)	0.250	2.524(0.807–7.895)	0.111
LNR(II)
LNR:0–0.2	1	0.029	1	0.002
0.2<LNR≤0.65	4.345(1.236–15.271)	0.022	4.242(1.873–9.604)	0.001
LNR>0.65	17.074(1.417–205.782)	0.025	4.604(1.254–16.895)	0.021
NLR
Low versus high	2.056(0.517–8.172)	0.306	–	–

Abbreviations: OS, overall survival; DFS, disease-free survival; cT and cN, clinical stages before neoadjuvant chemotherapy (NAC); pCR, pathological complete response; LNR, positive lymph node ratio; NLR, neutrophil-to-lymphocyte ratio.