Background
Methods
Patient background
Histopathological evaluation of TIL density
Ethics statement
Statistical methods
Results
Clinicopathological features and differences according to subtype
Parameters (n = 338) | Number of patients (%) |
---|---|
Age (years old) | 55 (24–78) |
Tumor size (mm) | 28.7 (9.2–119.8) |
Skin infiltration | |
Negative / Positive | 288 (85.2%) / 50 (14.8%) |
Lymph node metastasis | |
N0 / N1 / N2 / N3 | 114 (33.7%) / 128 (37.9%) / 63 (18.6%) / 33(9.8%) |
Estrogen receptor | |
Negative / Positive | 187 (55.3%) / 151 (44.7%) |
Progesterone receptor | |
Negative / Positive | 236 (69.8%) / 102 (30.2%) |
HER2 | |
Negative / Positive | 214 (63.3%) / 124 (36.7%) |
Ki67 | |
≤ 15% / > 15% | 105 (31.1%) / 233 (68.9%) |
Intrinsic subtype | |
Luminal BC / HER2BC / TNBC | 155 (45.8%) / 78 (23.1%) / 105 (31.1%) |
Objective response rate | |
Non-Responders / Responders | 40 (11.8%) / 298 (88.2%) |
Pathological response | |
Non-pCR / pCR | 222 (65.7%) / 116 (34.3%) |
TILs | |
Low / High | 180 (53.3%) / 158 (46.7%) |
Hypertension | |
No / Yes | 273 (80.8%) / 65 (19.2%) |
Number of medicine types for hypertension | |
0 / 1 / 2 / 3 | 273 (80.8%) / 41 (12.1%) / 21 (6.2%) / 2 (0.6%) / 1 (0.3%) |
Calcium channel blockers | |
No / Yes | 297 (87.9%) / 41 (12.1%) |
ACEi or ARBs | |
No / Yes | 305 (90.2%) / 33 (9.8%) |
Beta-blockers | |
No / Yes | 326 (96.4%) / 12 (3.6%) |
Diuretics | |
No / Yes | 331 (97.9%) / 7 (2.1%) |
Differences in clinicopathological features due to TILs or hypertension treatment
Parameters | All case (n = 338) | TNBC (n = 105) | HER2BC (n = 78) | ||||||
---|---|---|---|---|---|---|---|---|---|
Calcium channel blockers | p value | Calcium channel blockers | p value | Calcium channel blockers | p value | ||||
No (n = 297) | Yes (n = 41) | No (n = 94) | Yes (n = 11) | No (n = 68) | Yes (n = 10) | ||||
Age (years old) | |||||||||
≤ 55 | 170 (57.2%) | 7 (17.1%) | < 0.001 | 59 (62.8%) | 2 (18.2%) | 0.004 | 27 (39.7%) | 2 (20.0%) | 0.234 |
> 55 | 127 (42.8%) | 34 (82.9%) | 35 (37.2%) | 9 (81.8%) | 41 (60.3%) | 8 (80.0%) | |||
Tumor size (mm) | |||||||||
≤ 50 | 258 (86.9%) | 36 (87.8%) | 0.868 | 82 (87.2%) | 8 (72.7%) | 0.197 | 60 (88.2%) | 10 (100.0%) | 0.258 |
> 50 | 39 (13.1%) | 5 (12.2%) | 12 (12.8%) | 3 (27.3%) | 8 (11.8%) | 0 (0.0%) | |||
Skin infiltration | |||||||||
Negative | 255 (85.9%) | 33 (80.5%) | 0.365 | 86 (91.5%) | 8 (72.7%) | 0.055 | 58 (85.3%) | 9 (90.0%) | 0.694 |
Positive | 42 (14.1%) | 8 (19.5%) | 8 (8.5%) | 3 (27.3%) | 10 (14.7%) | 1 (10.0%) | |||
Lymph node status | |||||||||
Negative | 102 (34.3%) | 12 (29.3%) | 0.887 | 28 (29.8%) | 4 (36.4%) | 0.658 | 28 (41.2%) | 4 (40.0%) | 0.945 |
Positive | 195 (65.7%) | 29 (70.7%) | 66 (70.2%) | 7 (63.6%) | 40 (58.8%) | 6 (60.0%) | |||
Estrogen receptor | |||||||||
Negative | 166 (55.9%) | 21 (51.2%) | – | – | – | – | – | – | |
Positive | 131 (44.1%) | 20 (48.8%) | 0.574 | – | – | – | – | ||
Progesterone receptor | |||||||||
Negative | 207 (69.7%) | 29 (70.7%) | 0.893 | – | – | – | – | – | – |
Positive | 90 (30.3%) | 12 (29.3%) | – | – | – | – | |||
HER2 | |||||||||
Negative | 190 (64.0%) | 24 (58.5%) | 0.500 | – | – | – | – | – | |
Positive | 107 (36.0%) | 17 (41.5%) | – | – | – | – | |||
Ki67 | |||||||||
≤ 15% | 87 (29.3%) | 18 (43.9%) | 0.058 | 16 (17.0%) | 2 (18.2%) | 0.924 | 15 (22.1%) | 5 (50.0%) | 0.060 |
> 15% | 210 (70.7%) | 23 (56.1%) | 78 (83.0%) | 9 (81.8%) | 53 (77.9%) | 5 (50.0%) | |||
Intrinsic subtype Luminal BC | |||||||||
HER2BC, TNBC | 162 (54.5%) | 21 51.2%) | 0.690 | – | – | – | – | – | |
Luminal BC | 135 (45.5%) | 20 (48.8%) | – | – | – | – | |||
Intrinsic subtype HER2BC | |||||||||
Luminal BC, TNBC | 229 (77.1%) | 31 (75.6%) | 0.832 | – | – | – | – | – | |
HER2BC | 68 (22.9%) | 10 (24.4%) | – | – | – | – | |||
Intrinsic subtype TNBC | |||||||||
Luminal BC, HER2BC | 203 (68.4%) | 30 (73.2%) | 0.5332 | – | – | – | – | – | |
TNBC | 94 (31.6%) | 11 (26.8%) | – | – | – | – | |||
Objective response rate | |||||||||
Non-Responders | 32 (10.8%) | 8 (19.5%) | 0.105 | 12 (12.8%) | 4 (36.4%) | 0.040 | 5 (7.4%) | 0 (0.0%) | 0.382 |
Responders | 265 (89.2%) | 33 (80.5%) | 82 (87.2%) | 7 (63.6%) | 63 (92.6%) | 10 (100.0%) | |||
Pathological response | |||||||||
Non-pCR | 195 (65.7%) | 27 (65.9%) | 0.980 | 53 (56.4%) | 7 (63.6%) | 0.649 | 33 (48.5%) | 2 (20.0%) | 0.093 |
pCR | 102 (34.3%) | 14 (34.1%) | 41 (43.6%) | 4 (36.4%) | 35 (51.5%) | 8 (80.0%) | |||
TILs | |||||||||
Low | 152 (51.2%) | 28 (68.3%) | 0.040 | 38 (40.4%) | 9 (81.8%) | 0.009 | 22 (32.4%) | 3 (30.0%) | 0.884 |
High | 145 (48.8%) | 13 (31.7%) | 56 (59.6%) | 2 (18.2%) | 46 (67.6%) | 7 (70.0%) | |||
Hypertension | |||||||||
No | 273 (91.9%) | 0 (0.0%) | < 0.001 | 90 (95.7%) | 0 (0.0%) | < 0.001 | 60 (88.2%) | 0 (0.0%) | < 0.001 |
Yes | 24 (8.1%) | 41 (100.0%) | 4 (4.3%) | 11 (100.0%) | 8 (11.8%) | 10 (100.0%) | |||
Multiple types of AHT | |||||||||
No | 293 (98.6%) | 21 (51.2%) | < 0.001 | 93 (98.9%) | 6 (54.5%) | < 0.001 | 67 (98.5%) | 4 (40.0%) | < 0.001 |
Yes | 4 (1.4%) | 20 (48.8%) | 1 (1.1%) | 5 (45.5%) | 1 (1.5%) | 6 (60.0%) | |||
ACEi or ARBs | |||||||||
No | 281 (94.6%) | 24 (58.5%) | < 0.001 | 91 (96.8%) | 8 (72.7%) | 0.001 | 62 (91.2%) | 4 (40.0%) | < 0.001 |
Yes | 16 (5.4%) | 17 (41.5%) | 3 (3.2%) | 3 (27.3%) | 6 (8.8%) | 6 (60.0%) | |||
Beta-blockers | |||||||||
No | 289 (97.3%) | 37 (90.2%) | 0.022 | 93 (98.9%) | 3 (27.3%) | < 0.001 | 66 (97.1%) | 10 (100.0%) | 0.589 |
Yes | 8 (2.7%) | 4 (9.8%) | 1 (1.1%) | 8 (72.7%) | 2 (2.9%) | 0 (0.0%) | |||
Diuretics | |||||||||
No | 293 (98.6%) | 38 (92.7%) | 0.012 | 93 (98.9%) | 10 (90.9%) | 0.066 | 67 (98.5%) | 10 (100.0%) | 0.704 |
Yes | 4 (1.4%) | 3 (7.3%) | 1 (1.1%) | 1 (9.1%) | 1 (1.5%) | 0 (0.0%) |
Influence of CCBs on DFS and OS
Parameters | Univarite analysis | Multivariate analysis | ||||
---|---|---|---|---|---|---|
Hazard ratio | 95% CI | p value | Hazard ratio | 95% CI | p value | |
Age at opetation (yr) | ||||||
≤ 55 vs > 55 | 0.758 | 0.320–1.682 | 0.501 | |||
Tumor size (mm) | ||||||
≤ 50 vs > 50 | 2.718 | 1.056–6.245 | 0.039 | 1.264 | 0.464–3.165 | 0.630 |
Skin infiltration | ||||||
Negative vs Positive | 2.349 | 0.781–5.806 | 0.118 | |||
Lymph node status | ||||||
Negative vs Positive | 2.664 | 0.922–11.261 | 0.073 | 1.954 | 0.634–8.522 | 0.263 |
Ki67 | ||||||
≤ 15% vs > 15% | 1.700 | 0.587–7.197 | 0.359 | |||
Objective response rate | ||||||
Non-Responders vs Responders | 0.146 | 0.065–0.342 | < 0.001 | 0.258 | 0.106–0.638 | 0.004 |
Pathological response | ||||||
Non-pCR vs pCR | 0.207 | 0.060–0.545 | 0.001 | 0.395 | 0.108–1.166 | 0.095 |
TILs | ||||||
Low vs High | 0.306 | 0.125–0.689 | 0.004 | 0.464 | 0.180–1.120 | 0.088 |
Hypertension | ||||||
No vs Yes | 2.212 | 0.735–5.476 | 0.145 | |||
Multiple types of AHT | ||||||
No vs Yes | 1.309 | 0.210–4.431 | 0.725 | |||
Calcium channel blockers | ||||||
No vs Yes | 1.601 | 0.379–4.627 | 0.472 | |||
ACEi or ARBs | ||||||
No vs Yes | 1.554 | 0.249–5.265 | 0.574 | |||
Beta-blockers | ||||||
No vs Yes | 0.894 | 0.050–4.229 | 0.911 | |||
Diuretics | ||||||
No vs Yes | 2.850 | 0.159–13.551 | 0.378 |
Parameters | Univarite analysis | Multivariate analysis | ||||
---|---|---|---|---|---|---|
Hazard ratio | 95% CI | p value | Hazard ratio | 95% CI | p value | |
Age at opetation (yr) | ||||||
≤ 55 vs > 55 | 0.581 | 0.182–1.603 | 0.302 | |||
Tumor size (mm) | ||||||
≤ 50 vs > 50 | 2.366 | 0.661–6.800 | 0.168 | |||
Skin infiltration | ||||||
Negative vs Positive | 2.948 | 0.822–8.488 | 0.091 | 3.321 | 0.891–10.307 | 0.071 |
Lymph node status | ||||||
Negative vs Positive | 2.269 | 0.631–14.474 | 0.233 | |||
Ki67 | ||||||
≤ 15% vs > 15% | 3.762 | 0.756–68.181 | 0.120 | |||
Objective response rate | ||||||
Non-Responders vs Responders | 0.090 | 0.032–0.244 | < 0.001 | 0.143 | 0.045–0.430 | 0.001 |
Pathological response | ||||||
Non-pCR vs pCR | 0.074 | 0.004–0.365 | < 0.001 | 0.143 | 0.008–0.799 | 0.024 |
TILs | ||||||
Low vs High | 0.411 | 0.140–1.109 | 0.079 | 0.903 | 0.288–2.654 | 0.855 |
Hypertension | ||||||
No vs Yes | 1.161 | 0.182–4.181 | 0.847 | |||
Multiple types of AHT | ||||||
No vs Yes | 0.928 | 0.051–4.609 | 0.942 | |||
Calcium channel blockers | ||||||
No vs Yes | 0.699 | 0.039–3.465 | 0.715 | |||
ACEi or ARBs | ||||||
No vs Yes | 1.161 | 0.064–5.759 | 0.887 | |||
Beta-blockers | ||||||
No vs Yes | – | – | 0.206 | |||
Diuretics | ||||||
No vs Yes | 4.138 | 0.228–20.631 | 0.258 |