Clinicopathological features
Table 1 shows the clinicopathological features of 332 patients with cT1N0-2M0 breast cancer who underwent surgery and 319 patients with cT1N0M0 breast cancer who underwent SLNB. Therefore, 13 patients (3.9%) were diagnosed with axillary lymph node metastases on imaging investigation (cN1: 11 patients (3.3%), cN2: 2 patients(0.6%)).In both groups, the median age was 59 (range, 29-79) years, and the median tumor diameter was 13 mm (range, 4.0-20.0 mm). In patients with cT1N0M0 breast cancer, 262 patients (82.1%) were positive for ER, 194 (60.8%) were positive for PgR, and 24 (7.5%) were positive for HER2. High Ki67 expression was observed in 123 patients (38.8%). The following results were demonstrated by the intrinsic subtypes: HR+HER2-BC: 255 patients (79.9%), HR+HER2+BC: 10 patients (3.1%), HER2-enriched BC 14 patients (4.4%), TNBC: 40 patients (12.5%). Pathologically, lymphatic invasion was observed in 95 patients (29.8%), and venous invasion in 13 patients (4.1%). Regarding the nuclear grade, only 36 patients (11.3%) were diagnosed with grade 3. These results did not differ significantly when compared with the entire group of cT1 patients undergoing surgery.
Table 1
Clinicopathological features of 332 patients who had surgery after being diagnosed with cT1N0-2M0 breast cancer, including 319 cT1N0M0 breast cancer.
Parameters
|
Number of all patients (n = 332) (%)
|
Number of cN0 patients (n = 319) (%)
|
Age at operation (years old)
|
median 59 (range, 29–79)
|
median 59 (range, 29–79)
|
Tumor size (mm)
|
median 13 (range, 4–20)
|
median 13 (range, 4–20)
|
Clinical lymph node metastasis
cN0 / cN1 / cN2
|
319 (96.1%) / 11 (3.3%) / 2 (0.6%)
|
-
|
Estrogen receptor
Negative / Positive
|
59 (17.8%) / 273 (82.2%)
|
57 (17.9%) / 262 (82.1%)
|
Progesterone receptor
Negative / Positive
|
130 (39.2%) / 202 (60.8%)
|
125 (39.2%) / 194 (60.8%)
|
HER2
Negative / Positive
|
306 (92.2%) / 26 (7.8%)
|
295 (92.5%) / 24 (7.5%)
|
Ki67
≤ 14% / >14%
|
206 (62.0%) / 126 (38.0%)
|
196 (61.4%) / 123 (38.6%)
|
Intrinsic subtype
HR + HER2-BC / HR + HER2 + BC
/ HER2enriched BC / TNBC
|
265 (79.8%) / 11 (3.3%)
/ 15 (4.5%) / 41 (12.4%)
|
255 (79.9%) / 10 (3.1%)
/ 14 (4.4%) / 40 (12.6%)
|
Lymphatic invasion
ly0 / ly1
|
229 (69.0%) / 103 (31.0%)
|
224 (70.2%) / 95 (29.8%)
|
Venous invasion
v0 / v1
|
318 (95.8%) / 14 (4.2%)
|
306 (95.9%) / 13 (4.1%)
|
Nuclear grade
1 / 2 / 3
|
164 (49.4%) / 129 (38.9%) / 39 (11.7%)
|
158 (49.5%) / 125 (39.2%) / 36 (11.3%)
|
Pathological lymph node metastasis
pN0 / pN1mic / pN1a / pN2
|
257 (77.4%) / 16 (4.8%) / 54 (16.3%) / 5 (1.5%)
|
257 (80.6%) / 16 (5.0%) / 46 (14.4%) / 0 (0.0%)
|
TILs (score)
0 / 1 / 2 / 3
|
29 (8.7%) / 243 (73.2%) / 57 (17.2%) / 3 (0.9%)
|
25 (7.8%) / 235 (73.7%) / 56 (17.6%) / 3 (0.9%)
|
HER2: human epidermal growth factor receptor 2. HR + HER2-BC: hormone receptor-positive and HER2 negative breast cancer (ER + and/or PgR+, and HER2-). HR + HER2 + BC: hormone receptor-positive and HER2 positive breast cancer (ER + and/or PgR+, and HER2+). HER2 enriched BC: human epidermal growth factor receptor 2-enriched breast cancer (ER-, PgR-, and HER2+). TNBC: triple negative breast cancer (ER-, PgR-, and HER2-). TILs: tumor- infiltrating lymphocytes. |
For SLNB, a median of 2 (range, 1-8) SLNs were identified and evaluated pathologically. There were 60 cases (19.4%) of SLNM (macrometastasis: 46 cases, micrometastasis: 16 cases). The intrinsic subtype of all breast cancers with micrometastasis was HR+HER2-BC. All patients who underwent axillary dissection due to lymph node metastasis on radiological examination had pathological metastasis to the lymph nodes.
When TIL densities were examined in the biopsied tissues, in cN0 cases, 25 patients (7.8%) had score 0, 235 (73.7%) had score 1, 56 (17.6%) had score 2, and three (0.9%) had score 3. In the 13 cases in which lymph node metastasis was detected by imaging, four patients had score 0, eight had score 1, and one had score 2.
Correlation between clinicopathological features and lymph node metastasis
The correlations between clinicopathological features and lymph node metastasis are listed in Table 2. Metastasis was significantly higher in breast cancers with tumor diameter >10 mm than in those with diameter 10 mm (p = 0.016). Additionally, metastasis was significantly associated with lymphatic invasion (p <0.001). These two clinicopathological factors correlated with SLNM even in patients diagnosed with cN0 (tumor size; p=0.017, lymphatic invasion; p=0.002) (Table 3).
Table 2
Correlation between lymph node metastasis and clinicopathological features in cT1 breast cancer patients undergoing surgery
Parameters
|
All intrinsic subtype (n = 332)
|
HR + HER2-BC (n = 265)
|
HR + HER2 + BC (n = 11)
|
HER2enriched BC (n = 15)
|
TNBC (n = 41)
|
pN0 or 1mic
(n = 273)
|
pN1a or 2
(n = 59)
|
p value
|
pN0 or 1mic
(n = 217)
|
pN1a or 2
(n = 48)
|
p value
|
pN0
(n = 9)
|
pN1a or 2
(n = 2)
|
p value
|
pN0
(n = 11)
|
pN1a or 2
(n = 4)
|
p value
|
pN0
(n = 36)
|
pN1a or 2
(n = 5)
|
p value
|
Age (years old)
≤ 60
> 60
|
158 (57.9%)
115 (42.1%)
|
28 (47.5%)
31 (52.5%)
|
0.144
|
130 (59.9%)
87 (40.1%)
|
23 (47.9%)
25 (52.1%)
|
0.128
|
5 (55.6%)
4 (44.4%)
|
1 (50.0%)
1 (50.0%)
|
0.887
|
7 (63.6%)
4 (36.4%)
|
3 (75.0%)
1 (25.0%)
|
0.680
|
16 (44.4%)
20 (55.6%)
|
1 (20.0%)
4 (80.0%)
|
0.299
|
Tumor size (mm)
≤ 10.0
> 10.0
|
54 (19.8%)
219 (80.2%)
|
4 (6.8%)
55 (93.2%)
|
0.016
|
45 (20.7%)
172 (79.8%)
|
4 (8.3%)
44 (91.7%)
|
0.045
|
2 (22.2%)
7 (77.8%)
|
0 (0.0%)
2 (100.0%)
|
0.461
|
0 (0.0%)
11 (100.0%)
|
0 (0.0%)
4 (100.0%)
|
1.000
|
7 (19.4%)
29 (80.6%)
|
0 (0.0%)
5 (100.0%)
|
0.279
|
Estrogen receptor
Negative
Positive
|
50 (18.3%)
223 (81.7%)
|
9 (15.3%)
50 (84.7%)
|
0.577
|
3 (1.4%)
214 (98.6%)
|
0 (0.0%)
48 (100.0%)
|
0.413
|
0 (0.0%)
9 (100.0%)
|
0 (0.0%)
2 (100.0%)
|
1.000
|
-
-
|
-
-
|
-
|
-
-
|
-
-
|
-
|
Progesterone receptor
Negative
Positive
|
109 (39.9%)
164 (60.1%)
|
21 (35.6%)
38 (64.4%)
|
0.538
|
58 (26.7%)
159 (73.3%)
|
11 (22.9%)
37 (77.1%)
|
0.586
|
4 (44.4%)
5 (55.6%)
|
1 (50.0%)
1 (50.0%)
|
0.887
|
-
-
|
-
-
|
-
|
-
-
|
-
-
|
-
|
Hormone receptor
Negative
Positive
|
47 (17.2%)
226 (82.8%)
|
9 (15.3%)
50 (84.7%)
|
0.715
|
-
-
|
-
-
|
-
|
-
-
|
-
-
|
-
|
-
-
|
-
-
|
-
|
-
-
|
-
-
|
-
|
HER2
Negative
Positive
|
253 (92.7%)
20 (7.3%)
|
53 (89.8%)
6 (10.2%)
|
0.461
|
-
-
|
-
-
|
-
|
-
-
|
-
-
|
-
|
-
-
|
-
-
|
-
|
-
-
|
-
-
|
-
|
Ki67
≤14%
>14%
|
166 (60.8%)
107 (39.2%)
|
40 (67.8%)
19 (32.2%)
|
0.316
|
148 (68.2%)
69 (31.8%)
|
37 (77.1%)
11 (22.9%)
|
0.225
|
3 (33.3%)
6 (66.7%)
|
0 (0.0%)
2 (100.0%)
|
0.338
|
1 (9.1%)
10 (90.9%)
|
0 (0.0%)
4 (100.0%)
|
0.533
|
22 (61.1%)
14 (38.9%)
|
3 (60.0%)
2 (40.0%)
|
0.962
|
Lymphatic invasion
ly0
ly1
|
201 (73.6%)
72 (26.4%)
|
28 (47.5%)
31 (52.5%)
|
< 0.001
|
158 (72.8%)
59 (27.2%)
|
25 (52.1%)
23 (47.9%)
|
0.005
|
7 (77.8%)
2 (22.2%)
|
1 (50.0%)
1 (50.0%)
|
0.425
|
8 (72.7%)
3 (27.3%)
|
0 (0.0%)
4 (100.0%)
|
0.013
|
28 (77.8%)
8 (22.2%)
|
2 (40.0%)
3 (60.0%)
|
0.074
|
Venous invasion
v0
v1
|
264 (96.7%)
9 (3.3%)
|
54 (91.5%)
5 (8.5%)
|
0.073
|
209 (96.3%)
8 (3.7%)
|
43 (89.6%)
5 (10.4%)
|
0.051
|
9 (100.0%)
0 (0.0%)
|
2 (100.0%)
0 (0.0%)
|
1.000
|
10 (90.9%)
1 (9.1%)
|
4 (100.0%)
0 (0.0%)
|
0.533
|
36 (100.0%)
0 (0.0%)
|
5 (100.0%)
0 (0.0%)
|
1.000
|
Nuclear grade
1, 2
3
|
243 (89.0%)
30 (11.0%)
|
50 (84.7%)
9 (15.3%)
|
0.356
|
203 (93.5%)
14 (6.5%)
|
42 (87.5%)
6 (12.5%)
|
0.151
|
9 (100.0%)
0 (0.0%)
|
2 (100.0%)
0 (0.0%)
|
1.000
|
7 (63.6%)
4 (36.4%)
|
1 (25.0%)
3 (75.0%)
|
0.185
|
24 (66.7%)
12 (33.3%)
|
5 (100.0%)
0 (0.0%)
|
0.125
|
TILs (score)
0, 1
2, 3
|
219 (80.2%)
54 (19.8%)
|
53 (89.8%)
6 (10.2%)
|
0.082
|
190 (87.6%)
27 (12.4%)
|
44 (91.7%)
4 (8.3%)
|
0.423
|
7 (77.8%)
2 (22.2%)
|
2 (100.0%)
0 (0.0%)
|
0.461
|
5 (45.5%)
6 (54.5%)
|
3 (75.0%)
1 (25.0%)
|
0.310
|
17 (47.2%)
19 (52.8%)
|
4 (80.0%)
1 (20.0%)
|
0.169
|
TILs (score)
0
1–3
|
12 (4.4%)
261 (95.6%)
|
17 (28.8%)
42 (71.2%)
|
< 0.001
|
11 (5.1%)
206 (94.9%)
|
14 (29.2%)
34 (70.8%)
|
< 0.001
|
0 (0.0%)
9 (100.0%)
|
0 (0.0%)
2 (100.0%)
|
1.000
|
0 (0.0%)
11 (100.0%)
|
1 (25.0%)
3 (75.0%)
|
0.086
|
1 (2.8%)
35 (97.2%)
|
2 (40.0%)
3 (60.0%)
|
0.003
|
HER: human epidermal growth factor receptor. HR + HER2-BC: hormone receptor-positive and HER2 negative breast cancer (ER + and/or PgR+, and HER2-). HR + HER2 + BC: hormone receptor-positive and HER2 positive breast cancer (ER + and/or PgR+, and HER2+). HER2 enriched BC: human epidermal growth factor receptor 2-enriched breast cancer (ER-, PgR-, and HER2+). TNBC: triple negative breast cancer (ER-, PgR-, and HER2-). TILs: tumor- infiltrating lymphocytes. |
Table 3
Correlation between lymph node metastasis and clinicopathological features in cT1N0M0 breast cancer patients undergoing SLNB
Parameters
|
All intrinsic subtype (n = 319)
|
HR + HER2-BC (n = 255)
|
HR + HER2 + BC (n = 10)
|
HER2enriched BC (n = 14)
|
TNBC (n = 40)
|
pN0 or 1mic
(n = 273)
|
pN1a or 2
(n = 46)
|
p value
|
pN0 or 1mic
(n = 217)
|
pN1a or 2
(n = 38)
|
p value
|
pN0
(n = 9)
|
pN1a or 2
(n = 1)
|
p value
|
pN0
(n = 11)
|
pN1a or 2
(n = 3)
|
p value
|
pN0
(n = 36)
|
pN1a or 2
(n = 4)
|
p value
|
Age (years old)
≤ 60
> 60
|
158 (57.9%)
115 (42.1%)
|
21 (45.7%)
25 (54.3%)
|
0.124
|
130 (59.9%)
87 (40.1%)
|
17 (44.7%)
21 (55.3%)
|
0.081
|
5 (55.6%)
4 (44.4%)
|
1 (100.0%)
0 (0.0%)
|
0.389
|
7 (63.6%)
4 (36.4%)
|
2 (66.7%)
1 (33.3%)
|
0.923
|
16 (44.4%)
20 (55.6%)
|
1 (25.0%)
3 (75.0%)
|
0.455
|
Tumor size (mm)
≤ 10.0
> 10.0
|
54 (19.8%)
219 (80.2%)
|
3 (6.5%)
43 (93.5%)
|
0.017
|
45 (20.7%)
172 (79.3%)
|
3 (7.9%)
35 (92.1%)
|
0.062
|
2 (22.2%)
7 (77.8%)
|
0 (0.0%)
1 (100.0%)
|
0.598
|
0 (0.0%)
11 (100.0%)
|
0 (0.0%)
3 (100.0%)
|
1.000
|
7 (19.4%)
29 (80.6%)
|
0 (0.0%)
4 (100.0%)
|
0.332
|
Estrogen receptor
Negative
Positive
|
50 (18.3%)
223 (81.7%)
|
7 (15.2%)
39 (84.8%)
|
0.606
|
3 (1.4%)
214 (98.6%)
|
0 (0.0%)
38 (100.0%)
|
0.466
|
0 (0.0%)
9 (100.0%)
|
0 (0.0%)
1 (100.0%)
|
1.000
|
-
-
|
-
-
|
|
-
-
|
-
-
|
|
Progesterone receptor
Negative
Positive
|
109 (39.9%)
164 (60.1%)
|
16 (34.8%)
30 (65.2%)
|
0.506
|
58 (26.7%)
159 (73.3%)
|
9 (23.7%)
29 (76.3%)
|
0.694
|
4 (44.4%)
5 (55.6%)
|
0 (0.0%)
1 (100.0%)
|
0.389
|
-
-
|
-
-
|
|
-
-
|
-
-
|
|
Hormone receptor
Negative
Positive
|
47 (17.2%)
226 (82.8%)
|
7 (15.2%)
39 (84.8%)
|
0.735
|
-
-
|
-
-
|
|
-
-
|
-
-
|
|
-
-
|
-
-
|
|
-
-
|
-
-
|
|
HER2
Negative
Positive
|
253 (92.7%)
20 (7.3%)
|
42 (91.3%)
4 (8.7%)
|
0.749
|
-
-
|
-
-
|
|
-
-
|
-
-
|
|
-
-
|
-
-
|
|
-
-
|
-
-
|
|
Ki67
≤14%
>14%
|
166 (60.8%)
107 (39.2%)
|
30 (65.2%)
16 (34.8%)
|
0.567
|
148 (68.2%)
69 (31.8%)
|
28 (73.7%)
10 (26.3%)
|
0.500
|
3 (33.3%)
6 (66.7%)
|
0 (0.0%)
1 (100.0%)
|
0.490
|
1 (9.1%)
10 (90.9%)
|
0 (0.0%)
3 (100.0%)
|
0.588
|
22 (61.1%)
14 (38.9%)
|
2 (50.0%)
2 (50.0%)
|
0.667
|
Lymphatic invasion
ly0
ly1
|
201 (73.6%)
72 (26.4%)
|
23 (50.0%)
23 (50.0%)
|
0.002
|
158 (72.8%)
59 (27.2%)
|
20 (52.6%)
18 (47.4%)
|
0.012
|
7 (77.8%)
2 (22.2%)
|
1 (100.0%)
0 (0.0%)
|
0.598
|
8 (72.7%)
3 (27.3%)
|
0 (0.0%)
3 (100.0%)
|
0.024
|
28 (77.8%)
8 (22.2%)
|
2 (50.0%)
2 (50.0%)
|
0.224
|
Venous invasion
v0
v1
|
264 (96.7%)
9 (3.3%)
|
42 (91.3%)
4 (8.7%)
|
0.124
|
209 (96.8%)
8 (3.7%)
|
34 (89.5%)
4 (10.5%)
|
0.066
|
9 (100.0%)
0 (0.0%)
|
1 (100.0%)
0 (0.0%)
|
1.000
|
10 (90.9%)
1 (9.1%)
|
3 (100.0%)
0 (0.0%)
|
0.588
|
36 (100.0%)
0 (0.0%)
|
4 (100.0%)
0 (0.0%)
|
1.000
|
Nuclear grade
1, 2
3
|
243 (89.0%)
30 (11.0%)
|
40 (87.0%)
6 (13.0%)
|
0.689
|
203 (93.5%)
14 (6.5%)
|
35 (92.1%)
3 (7.9%)
|
0.742
|
9 (100.0%)
0 (0.0%)
|
1 (100.0%)
0 (0.0%)
|
1.000
|
7 (63.6%)
4 (36.4%)
|
0 (0.0%)
3 (100.0%)
|
0.051
|
24 (66.7%)
12 (33.3%)
|
4 (100.0%)
0 (0.0%)
|
0.168
|
TILs (score)
0, 1
2, 3
|
219 (80.2%)
54 (19.8%)
|
41 (89.1%)
5 (10.9%)
|
0.128
|
190 (87.6%)
27 (12.4%)
|
35 (92.1%)
3 (7.9%)
|
0.422
|
7 (77.8%)
2 (22.2%)
|
1 (100.0%)
0 (0.0%)
|
0.598
|
5 (45.5%)
6 (54.5%)
|
2 (66.7%)
1 (33.3%)
|
0.515
|
17 (47.2%)
19 (52.8%)
|
3 (75.0%)
1 (25.0%)
|
0.292
|
TILs (score)
0
1–3
|
12 (4.4%)
261 (95.6%)
|
13 (28.3%)
33 (71.7%)
|
< 0.001
|
11 (5.1%)
206 (94.9%)
|
11 (28.9%)
27 (71.1%)
|
< 0.001
|
0 (0.0%)
9 (100.0%)
|
0 (0.0%)
1 (100.0%)
|
1.000
|
0 (0.0%)
11 (100.0%)
|
1 (33.3%)
2 (66.7%)
|
0.047
|
1 (2.8%)
35 (97.2%)
|
1 (25.0%)
3 (75.0%)
|
0.053
|
SLNB: sentinel lymph node biopsy. HER: human epidermal growth factor receptor. HR + HER2-BC: hormone receptor-positive and HER2 negative breast cancer (ER + and/or PgR+, and HER2-). HR + HER2 + BC: hormone receptor-positive and HER2 positive breast cancer (ER + and/or PgR+, and HER2+). HER2 enriched BC: human epidermal growth factor receptor 2-enriched breast cancer (ER-, PgR-, and HER2+). TNBC: triple negative breast cancer (ER-, PgR-, and HER2-). TILs: tumor- infiltrating lymphocytes. |
Correlation between clinicopathological features and TILs
We examined the correlation between clinicopathological features and TILs in cN0 breast cancer cases (Table 4). When the patients were divided into TIL density score 0-1 and score 2-3, that is, a cut-off value of 10% was used for division into the higher group and lower group, the lower group correlated with the following clinicopathological factors; ER positive (p<0.001), PgR positive (p<0.001), HER2 negative (p=0.013), Ki67 high (p=0.002), nuclear grade high (p=0.015). However, if the patients were divided into TIL density score 0 and score 1-3, that is, by the presence or absence of TIL density, correlation with these clinicopathological factors was not observed. When examined by intrinsic subtype, in HR+HER2-BC, patients with TILs density score 0 were significantly more aged (p = 0.035) and had a larger tumor size (p = 0.020) than in patients with TILs density score 1-3 (Additional file 1). In HER2-enriched BC, the frequency of venous invasion was significantly higher in patients with TILs density score 0 than in patients with TILs density score 1-3 (p = 0.011). However, SLNM was significant in breast cancer with absent TIL density (p<0.001). When examined by intrinsic subtypes, HR+HER-2BC and HER2-enriched BC significantly correlated with SLNM, and TNBC also showed a similar tendency (HR+HER2-BC: p <0.001, HER2-enriched BC: p=0.047, TNBC: p=0.053) (Table 3).
Table 4
Correlation between TILs and clinicopathological features in cT1N0M0 breast cancer patients undergoing SLNB
Parameters
|
tumor- infiltrating lymphocytes (n = 319)
|
Score 0
(n = 25)
|
Score 1–3
(n = 294)
|
p value
|
Score 0, 1
(n = 260)
|
Score 2, 3
(n = 59)
|
p value
|
Age (years old)
≤ 60
> 60
|
10 (40.0%)
15 (60.0%)
|
169 (57.5%)
125 (42.5%)
|
0.091
|
144 (55.4%)
116 (44.6%)
|
35 (59.3%)
24 (40.7%)
|
0.582
|
Tumor size (mm)
≤ 10.0
> 10.0
|
1 (4.0%)
24 (96.0%)
|
56 (19.0%)
238 (81.0%)
|
0.059
|
49 (18.8%)
211 (81.2%)
|
8 (13.6%)
51 (86.4%)
|
0.339
|
Estrogen receptor
Negative
Positive
|
3 (12.0%)
22 (88.0%)
|
54 (18.4%)
240 (81.6%)
|
0.425
|
29 (11.2%)
231 (88.8%)
|
28 (47.5%)
31 (52.5%)
|
< 0.001
|
Progesterone receptor
Negative
Positive
|
9 (36.0%)
16 (64.0%)
|
116 (39.5%)
178 (60.5%)
|
0.734
|
88 (33.8%)
172 (66.2%)
|
37 (62.7%)
22 (37.3%)
|
< 0.001
|
Hormone receptor
Negative
Positive
|
3 (12.0%)
22 (88.0%)
|
51 (17.3%)
243 (82.7%))
|
0.494
|
27 (10.4%)
233 (89.6%)
|
27 (45.8%)
32 (54.2%)
|
< 0.001
|
HER2
Negative
Positive
|
24 (96.0%)
1 (4.0%)
|
271 (92.2%)
23 (7.8%)
|
0.487
|
245 (94.2%)
15 (5.8%)
|
50 (84.7%)
9 (15.3%)
|
0.013
|
Ki67
≤14%
>14%
|
19 (76.0%)
6 (24.0%)
|
177 (60.2%)
117 (39.8%)
|
0.119
|
170 (65.4%)
90 (34.6%)
|
26 (44.1%)
33 (55.9%)
|
0.002
|
Lymphatic invasion
ly0
ly1
|
19 (56.0%)
11 (44.0%)
|
210 (71.4%)
84 (28.6%)
|
0.105
|
182 (70.0%)
78 (30.0%)
|
42 (71.2%)
17 (28.8%)
|
0.857
|
Venous invasion
v0
v1
|
25 (100.0%)
0 (0.0%)
|
281 (95.6%)
13 (4.4%)
|
0.283
|
252 (96.9%)
8 (3.1%)
|
54 (91.5%)
5 (8.5%)
|
0.058
|
Nuclear grade
1, 2
3
|
24 (96.0%)
1 (4.0%)
|
259 (88.1%)
35 (11.9%)
|
0.230
|
236 (90.8%)
24 (9.2%)
|
47 (79.7%)
12 (20.3%)
|
0.015
|
Pathological lymph node metastasis
pN0 / pN1mic
pN1a / pN2
|
12 (48.0%)
13 (52.0%)
|
261 (88.8%)
33 (11.2%)
|
< 0.001
|
219 (84.2%)
41 (15.8%)
|
54 (91.5%)
5 (8.5%)
|
0.150
|
TILs: tumor- infiltrating lymphocytes. SLNB: sentinel lymph node biopsy. HER: human epidermal growth factor receptor. |
TIL density was significantly lower in patients with lymph node metastasis than in those without it in all cT1 patients (p = 0.018) (Fig. 2). When examined by intrinsic subtype, there was no significant difference between the subtypes. Moreover, no significant difference was observed in all cases when focusing on cN0 cases (p=0.061) (Fig. 3).
Based on these results, multivariate analysis for SLNM predictors revealed that lymphatic invasion (p=0.008, OR=2.522) and TILs (p<0.001, OR=0.137) were independent factors for prediction of SLNM (Table 5).
Table 5
Univariate and multivariate analysis with sentinel lymph node metastasis for cT1N0M0 breast cancer.
|
Univarite analysis
|
|
Multivarite analysis
|
Parameters
|
Odd ratio
|
95% CI
|
p value
|
|
Odd ratio
|
95% CI
|
p value
|
Age at operation (years old)
≤ 60 vs > 60
|
1.636
|
0.873–3.065
|
0.124
|
|
|
|
|
Tumor size (mm)
≤ 10.0 vs > 10.0
|
3.534
|
1.056–11.825
|
0.017
|
|
2.639
|
0.888–11.346
|
0.085
|
Estrogen receptor
Negative vs Positive
|
1.249
|
0.528–2.955
|
0.606
|
|
|
|
|
Progesterone receptor
Negative vs Positive
|
1.246
|
0.648–2.395
|
0.506
|
|
|
|
|
Hormone receptor
Negative vs Positive
|
1.159
|
0.488–2.748
|
0.735
|
|
|
|
|
HER2
Negative vs Positive
|
1.205
|
0.392-3.700
|
0.749
|
|
|
|
|
Ki67
≤14% vs > 14%
|
0.827
|
0.430–1.590
|
0.567
|
|
|
|
|
Lymphatic invasion
ly0 vs ly1
|
2.792
|
1.476–5.282
|
0.002
|
|
2.522
|
1.280–4.973
|
0.008
|
Venous invasion
v0 vs v1
|
2.794
|
0.823–9.481
|
0.124
|
|
|
|
|
Nuclear grade
1, 2 vs 3
|
1.215
|
0.475–3.105
|
0.689
|
|
|
|
|
TILs
0, 1 vs 2, 3
|
0.495
|
0.187–1.311
|
0.128
|
|
|
|
|
TILs
0 vs 1–3
|
0.117
|
0.049–0.277
|
< 0.001
|
|
0.137
|
0.055–0.335
|
< 0.001
|
CI: confidence intervals. HER2: human epidermal growth factor receptor 2. TILs: tumor- infiltrating lymphocytes. |