1Division of Medical Oncology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
2Cancer Research Institute, The Catholic University of Korea, Seoul, Korea
3Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea
Copyright © 2019 by the Korean Cancer Association
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Values are presented as median (range) or number (%). NLR, neutrophil-to-lymphocyte ratio; AC, adriamycin-cyclophosphamide; DA, docetaxel-adriamycin; CMF, cyclophosphamide–methotrexate–5-fluorouracil; TC, docetaxel-cyclophosphamide; TAC, docetaxel-adriamycin-cyclophosphamide; FEC, 5-fluorouracil–epirubicin–cyclophosphamide.
Total | NLR ≤ 3.16 | NLR > 3.16 | p-value | |
---|---|---|---|---|
No. of patients | 358 | 313 (87.4) | 45 (12.6) | |
NLR | 1.76 (0.12-10.06) | 1.64 (0.12-3.16) | 3.95 (3.2-10.06) | |
Age (yr) | ||||
Median (range) | 51 (14-86) | 51 (14-86) | 48 (32-83) | 0.970 |
< 40 | 71 (19.8) | 62 (17.3) | 9 (2.5) | |
≥ 40 | 287 (80.2) | 251 (70.1) | 36 (10.1) | |
Stage | ||||
I | 127 (35.5) | 113 (31.6) | 14 (3.9) | 0.340 |
II | 164 (45.8) | 145 (40.5) | 19 (5.3) | |
III | 67 (18.7) | 55 (15.3) | 12 (3.4) | |
Histology | ||||
Invasive ductal carcinoma | 300 (83.8) | 260 (72.6) | 40 (11.2) | 0.460 |
Invasive lobular carcinoma | 6 (1.7) | 6 (1.7) | 0 | |
Medullary carcinoma | 17 (4.7) | 14 (3.9) | 3 (0.8) | |
Metaplastic carcinoma | 17 (4.7) | 16 (4.4) | 1 (0.3) | |
Others | 4 (1.1) | 4 (1.1) | 0 | |
Histologic grade | ||||
Well-moderately differentiated | 103 (28.8) | 86 (24.0) | 17 (4.8) | 0.408 |
Poorly differentiated | 252 (70.4) | 224 (62.6) | 28 (7.8) | |
Unknown | 3 (0.8) | 3 (0.8) | 0 | |
Ki-67 | ||||
< 20% | 48 (13.4) | 43 (12.0) | 5 (1.4) | 0.677 |
≥ 20% | 303 (84.6) | 265 (74.0) | 38 (10.6) | |
Unknown | 7 (2.0) | 5 (1.4) | 2 (0.6) | |
Adjuvant chemotherapy | 310 (86.6) | 271 (75.7) | 39 (10.9) | 0.540 |
AC followed by docetaxel | 64 (17.9) | 59 (16.4) | 5 (1.5) | |
AC | 171 (47.8) | 149 (41.6) | 22 (6.2) | |
DA | 14 (3.9) | 8 (2.2) | 6 (1.7) | |
CMF | 47 (13.1) | 42 (11.7) | 5 (1.4) | |
TC | 11 (3.1) | 10 (2.8) | 1 (0.3) | |
TAC | 2 (0.6) | 2 (0.6) | 0 | |
FEC | 1 (0.3) | 1 (0.3) | 0 | |
Adjuvant radiation | ||||
Yes | 267 (74.6) | 234 (65.4) | 33 (9.2) | 0.900 |
No | 91 (25.4) | 79 (22.1) | 12 (3.3) | |
Cancer recurrence | 47 (13.1) | 37 (10.3) | 10 (2.8) | 0.047 |
Death | 36 (10.1) | 26 (7.3) | 10 (2.8) | 0.004 |
Total | NLR ≤ 3.16 | NLR > 3.16 | p-value | |
---|---|---|---|---|
No. of patients | 50 | 42 (84) | 8 (16) | 0.430 |
Age (yr) | ||||
Median (range) | 43.5 (25-66) | 43.5 (36-51) | 0.600 | |
< 40 | 15 (30) | 13 (26) | 2 (4) | |
≥ 40 | 35 (70) | 29 (58) | 6 (12) | |
Clinical stage | ||||
II | 9 (18) | 9 (18) | 0 | 0.150 |
III | 41 (82) | 33 (66) | 8 (16) | |
Pathologic stage | ||||
0 | 3 (6) | 3 (6) | 0 | 0.260 |
I | 7 (14) | 6 (12) | 1 (2) | |
II | 16 (32) | 12 (24) | 4 (8) | |
III | 14 (28) | 11 (22) | 3 (6) | |
Downstaging | ||||
No | 6 (12) | 4 (8) | 2 (4) | 0.500 |
Yes | 44 (88) | 38 (76) | 6 (12) | |
pCR | 5 (10) | 5 (10) | 0 | 0.300 |
Neoadjuvant chemotherapy | ||||
AC | 13 (26) | 11 (22) | 2 (4) | 0.870 |
EC | 5 (10) | 5 (10) | 0 | |
DA | 32 (64) | 26 (52) | 6 (12) | |
Adjuvant radiation | ||||
Yes | 36 (72) | 29 (58) | 7 (14) | 0.400 |
No | 14 (28) | 13 (26) | 1 (2) | |
Cancer recurrence | 9 (18) | 6 (12) | 3 (6) | 0.500 |
Death | 8 (16) | 6 (12) | 2 (4) | 0.450 |
Characteristic | Overall survival |
Disease-free survival |
||||||
---|---|---|---|---|---|---|---|---|
Univariate analysis |
Multivariate analysis |
Univariate analysis |
Multivariate analysis |
|||||
HR (95% CI) | p-value | HR (95% CI) | p-value | HR (95% CI) | p-value | HR (95% CI) | p-value | |
Age (yr) | ||||||||
≥ 40 vs. < 40 | 1.167 (0.6-2.67) | 0.720 | - | - | 0.83 (0.42-1.63) | 0.580 | - | - |
Stage | ||||||||
I | 1 (reference) | < 0.001 | 1 (reference) | 0.114 | 1 (reference) | < 0.001 | 1 (reference) | < 0.001 |
II vs. I | 2.13 (0.84-5.45) | 0.110 | 3.15 (1.03-9.68) | 0.045 | 1.41 (0.67-2.97) | 0.361 | 1.33 (0.61-2.95) | 0.470 |
III vs. I | 5.97 (2.23-15.6) | < 0.001 | 3.12 (0.96-10.01) | 0.058 | 4.07 (1.91-8.72) | < 0.001 | 4.0 (1.81-8.85) | 0.001 |
NLR | ||||||||
> 3.16 vs. ≤ 3.16 | 2.97 (1.43-6.17) | 0.003 | 3.15 (1.3-7.5) | 0.009 | 2.11 (1.05-4.25) | 0.036 | 1.73 (0.83-3.6) | 0.140 |
Ki-67 (%) | ||||||||
≥ 20 vs. < 20 | 3.11 (0.74-13.1) | 0.120 | 3.68 (0.87-15.7) | 0.070 | 1.003 (0.44-2.26) | 0.994 | - | - |
History of adjuvant chemotherapy | ||||||||
Yes vs. no | 1.57 (0.48-5.14) | 0.460 | - | - | 2.18 (0.68-7.04) | 0.190 | - | - |
Cancer recurrence | ||||||||
Yes vs. no | 55.9 (19.7-159.2) | < 0.001 | 58.2 (19.76-171.4) | < 0.001 | - | - | - | - |
Characteristic | Univariate analysis |
Multivariate analysis |
||
---|---|---|---|---|
Hazard ratio (95% CI) | p-value | Hazard ratio (95% CI) | p-value | |
Age (yr) | ||||
< 40 vs. ≥ 40 | 1.07 (0.33-3.42) | 0.900 | - | - |
Clinical stage | ||||
II vs. III | 3.76 (0.49-28.85) | 0.200 | - | - |
Surgical stage | 0.034 | 0.027 | ||
0 vs. I | 0.51 (0.046-5.65) | 0.590 | 0.37 (0.33-4.24) | 0.430 |
0 vs. II | 0.5 (0.052-4.83) | 0.550 | 0.39 (0.4-3.84) | 0.420 |
0 vs. III | 2.74 (0.34-22.08) | 0.340 | 2.22 (0.27-18.0) | 0.450 |
Downstaging | ||||
No vs. yes | 0.55 (0.19-1.59) | 0.270 | - | - |
pCR | ||||
No vs. yes | 0.62 (0.08-4.7) | 0.640 | - | - |
Baseline NLR | ||||
≤ 3.16 vs. > 3.16 | 1.8 (0.5-6.5) | 0.360 | - | - |
NLR change (%) | ||||
–30% < NLR change < 100% vs. NLR < –30% or > 100% | 3.81 (1.19-12.15) | 0.024 | 4.1 (1.27-13.16) | 0.018 |
Ki-67 (%) | ||||
< 20 vs. ≥ 20 | 1.29 (0.36-4.64) | 0.690 | - | - |
Baseline tumor tissue | Tumor tissue after neoadjuvant chemotherapy | |
---|---|---|
No. of patients | 34 | 30 |
Distribution of sTIL | 10 (3-35) | 11.5 (5-60) |
CD4 | 74.6 (9.8-226) | 67.8 (11.6-250.6) |
CD8 | 61.2 (6-166.8) | 85 (19.6-189) |
FOXP3 | 12.4 (1.8-54.6) | 10.2 (1-41) |
CD8/FOXP3 ratio | 4.21 (1.2-44.9) | 7.66 (2.96-26.4) |
PD-L1 (tumor cell) | ||
Median (range) | 1.5 (0-200) | 2 (0-270) |
≥ 1 | 20 (58.8) | 17 (56.7) |
≥ 5 | 15 (44.1) | 14 (46.7) |
PD-L1 (stromal cell) | ||
Median (range) | 8.5 (0-90) | 17.5 (0-125) |
≥ 1 | 30 (88.2) | 24 (80.0) |
≥ 5 | 21 (61.8) | 21 (70.0) |
TIL change during NAC | ||
Same or increased | 21 (70.0) | |
Decreased | 9 (30.0) | |
TIL fold change during NAC | ||
Median (range) | 1.25 (0.5-8.33) | |
PD-L1 change during NAC | ||
Negative or negative conversion in tumor | 12 (35.3) | |
Negative or negative conversion in stroma | 4 (13.3) |
Values are presented as median (range) or number (%). NLR, neutrophil-to-lymphocyte ratio; AC, adriamycin-cyclophosphamide; DA, docetaxel-adriamycin; CMF, cyclophosphamide–methotrexate–5-fluorouracil; TC, docetaxel-cyclophosphamide; TAC, docetaxel-adriamycin-cyclophosphamide; FEC, 5-fluorouracil–epirubicin–cyclophosphamide.
Values are presented as number (%) unless otherwise indicated. NLR, neutrophil-to-lymphocyte ratio; pCR, pathologic compete response; AC, adriamycin-cyclophosphamide; EC, epirubicin-cyclophosphamide; DA, docetaxel-adriamycin.
HR, hazard ratio; CI, confidence interval; NLR, neutrophil-to-lymphocyte ratio.
CI, confidence interval; pCR, pathologic complete response; NLR, neutrophil-to-lymphocyte ratio.
Value are presented as median (range) or number (%). TIL, tumor-infiltrating lymphocyte; PD-L1, programmed death-ligand 1; sTIL, stromal TIL; FOXP3, forkhead box P3; NAC, neoadjuvant chemotherapy.