Table 1 . Comparison of clinicopathologic and US characteristics between the training and validation cohorts
Characteristics
|
SYSUCC
n=607
|
FMUCH
N=242
|
p-value
|
Age
|
47.16±10.48
|
49.86±9.52
|
<0.001
|
Menopausal status
|
|
|
0.019
|
Pre/perimenopausal
|
377 (62.1%)
|
171 (70.7%)
|
|
Postmenopausal
|
230 (37.9%)
|
71 (29.3%)
|
|
Tumor stage
|
|
|
0.074
|
1
|
49 (8.1%)
|
21 (8.7%)
|
|
2
|
314 (51.7%)
|
141 (58.3%)
|
|
3
|
142 (23.4%)
|
37 (16.3%)
|
|
4
|
102 (16.8%)
|
43 (17.8%)
|
|
Nodal stage
|
|
|
<0.001
|
1
|
180 (29.7%)
|
160 (66.1%)
|
|
2
|
226 (37.2%)
|
58 (24.0%)
|
|
3
|
201 (33.1%)
|
24 (9.9%)
|
|
ER status
|
|
|
0.708
|
Negative
|
205 (33.8%)
|
85 (35.1%)
|
|
Positive
|
402 (66.2%)
|
157 (64.9%)
|
|
PR status
|
|
|
0.572
|
Negative
|
248 (40.9%)
|
104 (43.0%)
|
|
Positive
|
359 (59.1%)
|
138 (57.0%)
|
|
HER2 status
|
|
|
0.001
|
Negative
|
327 (53.9%)
|
162 (66.9%)
|
|
Positive
|
280 (46.1%)
|
80 (33.1%)
|
|
Ki-67
|
38.73±21.67
|
42.22±23.53
|
0.041
|
Location of breast tumor
|
|
|
0.142
|
No residual disease on the lateral part of breast
|
130 (21.4%)
|
41 (16.9%)
|
|
Residual tumor on the lateral part of breast
|
477 (78.6%)
|
201 (83.1%)
|
|
Number of primary tumor
|
|
|
0.054
|
Solitary disease
|
497 (81.9%)
|
184 (76.0%)
|
|
Multifocal disease
|
110 (18.1%)
|
58 (24.0%)
|
|
Tumor diameter before NAC(mm)
|
42.43±19.84
|
36.94±18.25
|
<0.001
|
Tumor diameter after NAC(mm)
|
23.93±16.26
|
22.37±14.71
|
0.339
|
Radiological response of breast tumor (%)*
|
41.32±35.95
|
33.48±50.19
|
0.006
|
Long diameter(mm)
|
14.04±6.97
|
12.29±4.69
|
0.002
|
Short diameter(mm)
|
6.91±4.11
|
6.30±2.63
|
0.078
|
Ratio of long /short diameter
|
2.15±0.75
|
2.03±0.61
|
0.120
|
Cortical thickness
|
|
|
0.373
|
≤3mm
|
303 (49.9%)
|
129 (53.3%)
|
|
>3mm
|
304 (50.1%)
|
113 (46.7%)
|
|
Shape
|
|
|
0.006
|
Oval
|
513 (84.5%)
|
188 (77.7%)
|
|
Round
|
32 (5.3%)
|
10 (4.1%)
|
|
Irregular
|
62 (10.2%)
|
44 (18.2%)
|
|
Margin
|
|
|
<0.001
|
Clear
|
591 (97.4%)
|
217 (89.7%)
|
|
Obscure
|
16 (2.6%)
|
36 (10.3%)
|
|
Fatty hilum
|
|
|
0.002
|
Absence
|
169 (27.8%)
|
43 (17.8%)
|
|
Presence
|
438 (72.2%)
|
199 (82.2%)
|
|
Microcalcification
|
|
|
0.546
|
Absence
|
578 (95.2%)
|
228 (94.2%)
|
|
Prsence
|
29 (4.8%)
|
14 (5.8%)
|
|
Values are expressed as the mean ± standard deviation or number.
US, ultrasound; SYSUCC, Sun Yat-Sen University Cancer Center; FMUCH, fujian medical university cancer hospital; ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor 2; NAC, neoadjuvant chemotherapy.
*Relative change in the largest diameter of primary tumor on US according to RECIST 1.1.
Table 2 . pCR and non-pCR rates of breast or axillary node after NAC
|
SYSUCC
|
FMUCH
|
|
B-pCR
(n=173)
|
- non pCR
(n=434)
|
p
|
B-pCR
(n=54)
|
- non pCR
(n=188)
|
p
|
N-pCR
|
149
|
153
|
<0.001
|
30
|
48
|
<0.001
|
N-non pCR
|
24
|
281
|
|
24
|
140
|
|
NAC, neoadjuvant chemotherapy; pCR, pathological complete response; SYSUCC, Sun Yat-Sen University Cancer Center; FMUCH, fujian medical university cancer hospital.
Table 3 . Univariate logistic regression analysis of characteristics predicting axillary response to NAC in node-positive breast cancer patients (n=607)
Characteristics
|
OR
|
95%CI
|
p-value
|
Age
|
1.02
|
1.01-1.03
|
0.005
|
Menopausal status
|
|
|
|
Pre/perimenopausal
|
-
|
-
|
|
Postmenopausal
|
1.08
|
0.81-1.43
|
0.591
|
Tumor stage
|
|
|
|
1
|
-
|
-
|
|
2
|
0.72
|
0.40-1.32
|
0.29
|
3
|
1.28
|
0.67-2.45
|
0.47
|
4
|
1.62
|
0.81-3.21
|
0.17
|
Nodal stage
|
|
|
|
1
|
-
|
-
|
|
2
|
4.02
|
2.62-6.15
|
<0.001
|
3
|
5.11
|
3.29-7.94
|
<0.001
|
ER status
|
|
|
|
Negative
|
-
|
-
|
|
Positive
|
2.35
|
1.76-3.15
|
<0.001
|
PR status
|
|
|
|
Negative
|
-
|
-
|
|
Positive
|
2.05
|
1.56-2.71
|
<0.001
|
HER2 status
|
|
|
|
Negative
|
-
|
-
|
|
Positive
|
0.36
|
0.27-0.47
|
<0.001
|
Ki-67
|
0.99
|
0.98-1.00
|
0.003
|
Location of breast tumor
|
|
|
|
No residual disease on the lateral part of breast
|
-
|
-
|
|
Residual tumor on the lateral part of breast
|
2.13
|
1.51-2.99
|
<0.001
|
Number of primary tumor
|
|
|
|
Solitary tumor
|
-
|
-
|
|
Multifocal disease
|
1.45
|
1.03-2.05
|
0.035
|
Tumor diameter before NAC
|
1
|
0.99-1.01
|
0.659
|
Tumor diameter after NAC
|
1.03
|
1.02-1.04
|
<0.001
|
Radiological response of breast tumor*
|
0.26
|
0.16-0.41
|
<0.001
|
Long diameter
|
1.02
|
1.00-1.05
|
0.037
|
Short diameter
|
1.22
|
1.15-1.3
|
<0.001
|
Ratio of long /short diameter
|
0.49
|
0.40-0.60
|
<0.001
|
Cortical thickness
|
|
|
|
≤3mm
|
-
|
-
|
|
>3mm
|
8.00
|
5.86-10.91
|
<0.001
|
Shape
|
|
|
|
Oval
|
-
|
-
|
|
Round
|
2.33
|
1.19-4.55
|
0.014
|
Irregular
|
11.25
|
5.59-22.63
|
<0.001
|
Margin
|
|
|
|
Clear
|
-
|
-
|
|
Obscure
|
8.05
|
2.84-22.79
|
<0.001
|
Fatty hilum
|
|
|
|
Presence
|
-
|
-
|
|
Absence
|
4.58
|
3.15-6.64
|
<0.001
|
Microcalcification
|
|
|
|
Absence
|
-
|
-
|
|
Prsence
|
6.61
|
2.58-16.97
|
<0.001
|
OR, odds ratio; CI, confidence interval; ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor 2; NAC, neoadjuvant chemotherapy.
*Relative change in the largest diameter of primary tumor on US according to RECIST 1.1.
Table 4 . Multivariate logistic regression analysis of characteristics predicting axillary response to NAC in node-positive breast cancer patients (n=607)
Characteristics
|
OR
|
95%CI
|
p-value
|
Age
|
1
|
0.98-1.03
|
0.769
|
Nodal stage
|
|
|
|
1
|
-
|
-
|
|
2
|
2.04
|
1.37-3.03
|
0.002
|
3
|
2.26
|
1.44-3.54
|
0.001
|
ER status
|
|
|
|
Negative
|
-
|
-
|
|
Positive
|
2.67
|
1.81-3.93
|
<0.001
|
PR status
|
|
|
|
Negative
|
-
|
-
|
|
Positive
|
1
|
0.57-1.75
|
0.995
|
HER2 status
|
|
|
|
Negative
|
-
|
-
|
|
Positive
|
0.32
|
0.22-0.45
|
<0.001
|
Ki-67
|
0.99
|
0.98-1.00
|
0.041
|
Location of breast tumor
|
|
|
|
No residual disease on the lateral part of breast
|
-
|
-
|
|
Residual tumor on the lateral part of breast
|
1.99
|
1.29-3.05
|
0.013
|
Number of breast tumor
|
|
|
|
Solitary tumor
|
-
|
-
|
|
Multifocal disease
|
1.16
|
0.64-2.09
|
0.633
|
Tumor diameter after NAC
|
1.00
|
0.97-1.02
|
0.716
|
Radiological response of breast tumor *
|
0.36
|
0.22-0.61
|
0.017
|
Long diameter
|
1.04
|
0.90-1.19
|
0.614
|
Short diameter
|
1.05
|
0.80-1.38
|
0.717
|
Ratio of long /short diameter
|
0.75
|
0.31-1.79
|
0.518
|
Cortical thickness
|
|
|
|
≤3mm
|
-
|
-
|
|
>3mm
|
5.93
|
4.11-8.57
|
<0.001
|
Shape
|
|
|
|
Oval
|
-
|
-
|
|
Round
|
3.09
|
1.15-8.30
|
0.003
|
Irregular
|
4.88
|
2.15-11.03
|
<0.001
|
Margin
|
|
|
|
Clear
|
-
|
-
|
|
Obscure
|
6.51
|
0.74-56.95
|
0.09
|
Fatty hilum
|
|
|
|
Presence
|
-
|
-
|
|
Absence
|
1.43
|
0.72-2.80
|
0.305
|
Microcalcification
|
|
|
|
Absence
|
-
|
-
|
|
Prsence
|
1.41
|
0.34-5.84
|
0.637
|
NAC, ; OR, odds ratio; CI, confidence interval; ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor 2; NAC, neoadjuvant chemotherapy.
*Relative change in the largest diameter of primary tumor on US according to RECIST 1.1.
Table 5 . Predictive performance of clinicopathologic model, US model and combined model in the training cohort (n=607)
Models
|
AUC
|
Sensitivity
|
Specificity
|
Youden index
|
Clinicopathologic model
|
0.72
|
73.13
|
62.83
|
0.36
|
US model
|
0.81
|
74.38
|
78.44
|
0.53
|
Combined model
|
0.86
|
85.94
|
76.58
|
0.63
|
AUC, area under the receiver operating characteristic curve; US, ultrasound.
Table 6 . Predictive performance of clinicopathologic model, US model and combined model in the external validation cohort (n=242)
Models
|
AUC
|
Sensitivity
|
Specificity
|
Youden index
|
Clinicopathologic model
|
0.68
|
74.50
|
53.15
|
0.28
|
US model
|
0.76
|
68.46
|
74.77
|
0.43
|
Combined model
|
0.82
|
81.88
|
62.16
|
0.44
|
AUC, area under the receiver operating characteristic curve; US, ultrasound.