Background
Methods
Study population
Immunohistochemistry and fluorescence in situ hybridization
Clinicopathological subtypes
Contrast-enhanced computed tomography and tumor enhancement patterns
Tumor samples and distribution of tumor microvessel density
Statistics
Results
Survival analysis grouping by clinicopathological subtype
Characteristic | Luminal A (n = 119) | Luminal B Ki67+ (n = 52) | Luminal B HER2 + (22) | HER2 overexpression (16) | TNBC (46) | Statistics | P |
---|---|---|---|---|---|---|---|
Age (years)
| 51.67 ± 10.10 | 50.88 ± 8.16 | 55.41 ± 8.98 | 52.13 ± 6.49 | 51.91 ± 10.90 | 0.896 | 0.467 |
Menopause
| 2.378 | 0.667 | |||||
Postmenopausal
| 56 | 24 | 14 | 7 | 22 | ||
Premenopausal
| 63 | 28 | 8 | 9 | 24 | ||
Family history
| 2.075 | 0.722 | |||||
No
| 109 | 49 | 21 | 16 | 42 | ||
Yes
| 10 | 3 | 1 | 0 | 4 | ||
Diameter
| 2.15 ± 0.98 | 2.32 ± 0.94 | 2.43 ± 1.07 | 3.09 ± 1.49 | 2.50 ± 1.18 | 3.292 | 0.012 |
Quadrant
| 16.851 | 0.395 | |||||
Areolar
| 3 | 1 | 0 | 0 | 1 | ||
Inner upper
| 28 | 8 | 0 | 2 | 7 | ||
Inner lower
| 14 | 5 | 1 | 2 | 3 | ||
Outer lower
| 21 | 11 | 3 | 2 | 6 | ||
Outer upper
| 53 | 27 | 18 | 10 | 29 | ||
Enhancement patterns
| 59.901 | 0.000 | |||||
Homogeneous
| 40(33.6%) | 18(34.6%) | 7(31.8%) | 5(31.3%) | 12(26.1%) | ||
Heterogeneous
| 71(59.7%) | 29(55.8%) | 8(36.4%) | 3(18.8%) | 10(21.7%) | ||
Peripherals
| 8(6.7%) | 5(9.6%) | 7(31.8%) | 8(50.0%) | 24(52.2%) | ||
Difference of MVD (Edge - Center)
| 3.12 ± 6.26 | 3.18 ± 7.95 | 7.61 ± 8.53 | 7.98 ± 8.97 | 10.23 ± 8.72 | 9.543 | 0.000 |
Grade of DMVD
| 42.300 | 0.000 | |||||
Uniform distribution
| 102(85.7%) | 44(84.6%) | 14(63.6%) | 6(37.5%) | 21(45.7%) | ||
Uneven distribution
| 17(14.3%) | 8(15.4%) | 8(36.4%) | 10(62.5%) | 25(54.3%) | ||
Histological grade
| 30.927 | 0.000 | |||||
I
| 37(31.1%) | 16(30.8%) | 0(0%) | 1(6.3%) | 9(19.6%) | ||
II
| 77(64.7%) | 29(55.8%) | 16(72.7%) | 10(62.5%) | 34(73.9%) | ||
III
| 5(4.2%) | 7(13.5%) | 6(27.3%) | 5(31.3%) | 3(6.5%) | ||
Cancer thrombosis
| 7.806 | 0.099 | |||||
Negative
| 89 | 41 | 11 | 10 | 34 | ||
Positive
| 30 | 11 | 11 | 6 | 12 | ||
Nodal metastasis
| 6.825 | 0.145 | |||||
Negative
| 60 | 24 | 8 | 3 | 23 | ||
Positive
| 59 | 28 | 14 | 13 | 23 | ||
Number of metastatic nodes
| 2.09 ± 4.16 | 2.94 ± 5.01 | 6.77 ± 9.63 | 11.88 ± 11.37 | 4.89 ± 9.70 | 9.167 | 0.000 |
Clinical stage
| 50.721 | 0.000 | |||||
I
| 33(27.7%) | 15(28.8%) | 1(4.5%) | 0(0%) | 10(21.7%) | ||
IIA
| 38(31.9%) | 11(21.2%) | 10(45.5%) | 4(25.0%) | 13(28.3%) | ||
IIB
| 39(32.8%) | 21(40.4%) | 4(18.2%) | 4(25.0%) | 16(34.8%) | ||
IIIA
| 7(5.9%) | 3(5.8%) | 3(13.6%) | 3(18.8%) | 2(4.3%) | ||
IIIB
| 1(0.8%) | 2(3.8%) | 2(9.1%) | 1(6.3%) | 1(2.2%) | ||
IIIC
| 1(0.8%) | 0(0%) | 2(9.1%) | 4(25%) | 4(8.7%) | ||
IV
| 0(0%) | 0(0%) | 0(0%) | 0(0%) | 0(0%) | ||
P53 (%)
| 27.76 ± 30.19 | 32.65 ± 34.17 | 41.55 ± 30.32 | 30.19 ± 32.23 | 35.50 ± 35.33 | 1.141 | 0.338 |
Operation
| 5.455 | 0.244 | |||||
Mastectomy
| 102 | 47 | 21 | 16 | 43 | ||
Tumorectomy
| 17 | 5 | 1 | 0 | 3 | ||
Chemotherapy program
| 49.253 | 0.002 | |||||
Not performed
| 1(0.8%) | 0(0%) | 0(0%) | 0(0%) | 1(2.2%) | ||
CMF
| 2(1.7%) | 0(0%) | 0(0%) | 0(0%) | 0(0%) | ||
CAF or AC
| 42(35.3%) | 17(32.7%) | 2(9.1%) | 0(0%) | 11(23.9%) | ||
CEF or EC
| 21(17.6%) | 12(23.1%) | 10(45.5%) | 5(31.3%) | 14(30.4%) | ||
T or TC or TP
| 42(35.3%) | 15(28.8%) | 4(18.2%) | 2(12.5%) | 13(28.3%) | ||
TAC or A-T
| 10(8.4%) | 8(15.4%) | 6(27.3%) | 9(56.3%) | 7(15.2%) | ||
Radiotherapy
| 6.682 | 0.154 | |||||
Not performed
| 67 | 27 | 10 | 4 | 27 | ||
Performed
| 52 | 25 | 12 | 12 | 19 | ||
Endocrine therapy
| 262.436 | 0.000 | |||||
Not performed
| 0(0%) | 0(0%) | 0(0%) | 16(100%) | 46(100%) | ||
TAM
| 75(63.0%) | 32(61.5%) | 12(54.5%) | 0(0%) | 0(0%) | ||
LHRH
| 11(9.2%) | 7(13.5%) | 0(0%) | 0(0%) | 0(0%) | ||
AI
| 33(27.7%) | 13(25.0%) | 10(45.5%) | 0(0%) | 0(0%) | ||
Targeted therapy
| 33.619 | 0.000 | |||||
Not performed
| 119(100%) | 52(100%) | 20(90.9%) | 13(81.3%) | 46(100%) | ||
Performed
| 0(0%) | 0(0%) | 2(9.1%) | 3(18.8%) | 0(0%) | ||
Overall survival
| 99.2% | 98.1% | 86.4% | 87.5% | 91.3% | 17.629 | 0.024 |
Event
| 1 | 1 | 3 | 2 | 4 | ||
Deaths
| 1 | 1 | 3 | 2 | 3 | ||
Lost to follow-up
| 0 | 0 | 0 | 0 | 1 | ||
Median survival time
| 54.0 | 48.0 | 36.0 | 29.4 | 35.2 | 31.845 | 0.000 |
Disease-free survival
| 98.3% | 94.3% | 72.7% | 75.0% | 82.6% | 56.588 | 0.001 |
Event
| 2 | 3 | 6 | 4 | 7 | ||
Local recurrence
| 0 | 1 | 0 | 0 | 0 | ||
Contralateral breast cancer
| 1 | 1 | 2 | 0 | 0 | ||
Lung metastasis
| 0 | 0 | 0 | 1 | 1 | ||
Hepatic metastasis
| 0 | 0 | 2 | 1 | 2 | ||
Brain metastasis
| 0 | 0 | 0 | 1 | 2 | ||
Multi-organ
| 1 | 1 | 2 | 1 | 2 | ||
Lost to Follow-up
| 0 | 0 | 0 | 0 | 1 | ||
Disease-free survival
| 54.0 | 48.0 | 35.4 | 22.5 | 31.7 | 59.248 | 0.000 |
Follow-up time
| 4.741 | 0.001 | |||||
Median
| 23.0 | 25.5 | 30.5 | 17.0 | 20.0 | ||
Range
| 12-59 | 12-49 | 12-38 | 12-25 | 12-53 |
Cox proportional hazards model (including CT tumor enhancement patterns)
Survival analysis grouping by tumor enhancement patterns
Characteristic | Homogeneous enhancement (n = 82) | Heterogeneous enhancement (121) | Peripheral enhancement (52) | Statistics | P |
---|---|---|---|---|---|
Age(years)
| 51.35 ± 8.51 | 52.24 ± 10.37 | 52.00 ± 9.53 | 0.210 | 0.811 |
Menopause
| 1.388 | 0.499 | |||
Postmenopausal
| 41 | 54 | 28 | ||
Premenopausal
| 41 | 67 | 24 | ||
Family history
| 1.095 | 0.579 | |||
No
| 76 | 111 | 50 | ||
Yes
| 6 | 10 | 2 | ||
Diameter
| 2.08 ± 0.91 | 2.31 ± 1.04 | 2.78 ± 1.28 | 7.028 | 0.001 |
Quadrant
| 12.629 | 0.125 | |||
Areolar
| 2 | 1 | 2 | ||
Inner upper
| 13 | 29 | 3 | ||
Inner lower
| 11 | 9 | 5 | ||
Outer lower
| 13 | 22 | 8 | ||
Outer upper
| 43 | 60 | 34 | ||
Difference of MVD (Edge - Center)
| -0.42 ± 5.72 | 3.73 ± 4.67 | 17.02 ± 3.88 | 211.273 | 0.000 |
Grade of DMVD
| 179.854 | 0.000 | |||
Uniform distribution
| 77(93.9%) | 110(90.9%) | 0(0%) | ||
Uneven distribution
| 5(6.1%) | 11(9.1%) | 52(100%) | ||
Histological grade
| 2.021 | 0.732 | |||
I
| 22 | 31 | 10 | ||
II
| 51 | 80 | 35 | ||
III
| 9 | 10 | 7 | ||
Cancer thrombosis
| 2.910 | 0.233 | |||
Negative
| 60 | 92 | 33 | ||
Positive
| 22 | 29 | 19 | ||
Nodal metastasis
| 1.588 | 0.452 | |||
Negative
| 25 | 61 | 22 | ||
Positive
| 47 | 60 | 30 | ||
Number of metastatic nodes
| 3.80 ± 6.88 | 2.51 ± 5.30 | 6.73 ± 10.17 | 6.540 | 0.002 |
Clinical stage
| 19.007 | 0.040 | |||
I
| 20(24.4%) | 32(26.4%) | 7(13.5%) | ||
IIA
| 25(30.5%) | 37(30.6%) | 14(26.9%) | ||
IIB
| 29(35.4%) | 38(31.4%) | 17(32.7%) | ||
IIIA
| 4(4.9%) | 10(8.3%) | 4(7.7%) | ||
IIIB
| 2(2.4%) | 2(1.7%) | 3(5.8%) | ||
IIIC
| 2(2.4%) | 2(1.7%) | 7(13.5%) | ||
IV
| 0(0%) | 0(0%) | 0(0%) | ||
ER
| 31.203 | 0.000 | |||
Negative
| 29(35.4%) | 32(26.4%) | 37(71.2%) | ||
Positive
| 53(64.6%) | 89(73.6%) | 15(28.8%) | ||
PgR
| 34.485 | 0.000 | |||
Negative
| 24(29.3%) | 29(24.0%) | 36(69.2%) | ||
Positive
| 58(70.7%) | 92(76.0%) | 16(30.8%) | ||
HER2
| 11.200 | 0.004 | |||
Negative
| 70(85.4%) | 110(90.9%) | 37(71.2%) | ||
Positive
| 12(14.6%) | 11(9.1%) | 15(28.8%) | ||
Ki67
| 14.736 | 0.001 | |||
Negative (<14%=
| 53(64.6%) | 77(63.6%) | 18(34.6%) | ||
Positive (>14%)
| 29(35.4%) | 44(36.4%) | 34(65.4%) | ||
P53 (%)
| 33.98 ± 32.59 | 30.35 ± 31.32 | 30.27 ± 33.83 | 0.357 | 0.700 |
Clinicopathological subtypes
| 59.901 | 0.000 | |||
Luminal A
| 40(48.8%) | 71(58.7%) | 8(15.4%) | ||
Luminal B (Ki67+)
| 18(22.0%) | 29(24.0%) | 5(9.6%) | ||
Luminal B (HER2+)
| 7(8.5%) | 8(6.6%) | 7(13.5%) | ||
HER2 overexpression
| 5(6.1%) | 3(2.5%) | 8(15.4%) | ||
TNBC
| 12(14.6%) | 10(8.3%) | 24(46.2%) | ||
Operation
| 4.885 | 0.087 | |||
Mastectomy
| 72 | 106 | 51 | ||
Tumorectomy
| 10 | 15 | 1 | ||
Chemotherapy program
| 14.344 | 0.279 | |||
Not performed
| 0 | 1 | 1 | ||
CMF
| 1 | 1 | 0 | ||
CAF or AC
| 23 | 42 | 7 | ||
CEF or EC
| 19 | 27 | 16 | ||
T or TC or TP
| 27 | 34 | 15 | ||
TAC or A-T
| 12 | 16 | 13 | ||
Radiotherapy
| 1.560 | 0.458 | |||
Not performed
| 40 | 69 | 26 | ||
Performed
| 42 | 52 | 26 | ||
Endocrine therapy
| 53.381 | 0.000 | |||
Not performed
| 17(20.7%) | 13(10.7%) | 32(61.5%) | ||
TAM
| 38(46.3%) | 68(56.2%) | 13(25.0%) | ||
LHRH
| 7(8.5%) | 8(6.6%) | 3(5.8%) | ||
AI
| 20(24.4%) | 32(26.4%) | 4(7.7%) | ||
Targeted therapy
| 2.329 | 0.312 | |||
Not performed
| 79 | 119 | 52 | ||
Performed
| 3 | 2 | 0 | ||
Overall survival
| 100% | 95.9% | 88.5% | 11.876 | 0.018 |
Event
| 0 | 5 | 6 | ||
Deaths
| 0 | 5 | 5 | ||
Lost to follow-up
| 0 | 0 | 1 | ||
Median survival time
| 54.0 | 54.0 | 42.0 | 8.525 | 0.014 |
Disease-free survival
| 100% | 95.9% | 65.4% | 63.908 | 0.000 |
Event
| 0 | 5 | 18 | ||
Local recurrence
| 0 | 0 | 1 | ||
Contralateral breast cancer
| 0 | 0 | 4 | ||
Lung metastasis
| 0 | 0 | 2 | ||
Hepatic metastasis
| 0 | 0 | 5 | ||
Brain metastasis
| 0 | 1 | 2 | ||
Multi-organ
| 0 | 4 | 3 | ||
Lost to follow-up
| 0 | 0 | 1 | ||
Disease-free survival
| 54.0 | 54.0 | 29.5 | 45.952 | 0.000 |
Follow-up time
| 2.967 | 0.053 | |||
Median
| 21.0 | 25.0 | 21.0 | ||
Range
| 12-56 | 12-59 | 12-44 |
Cox proportional hazards model (including MVD distribution)
Survival analysis grouping by grade of DMVD
Characteristic | Uniform distribution (DMVD < 10) (n = 187) | Uneven distribution (DMVD > 10) (68) | Statistics | P |
---|---|---|---|---|
Age (years)
| 51.86 ± 9.55 | 52.04 ± 9.84 | -0.138 | 0.890 |
Menopause
| 0.389 | 0.572 | ||
Postmenopausal
| 88 | 35 | ||
Premenopausal
| 99 | 33 | ||
Family history
| 0.012 | 1.000 | ||
No
| 174 | 63 | ||
Yes
| 13 | 5 | ||
Diameter
| 2.21 ± 0.95 | 2.67 ± 1.31 | -3.061 | 0.002 |
Quadrant
| 5.680 | 0.224 | ||
Areolar
| 3 | 2 | ||
Inner upper
| 39 | 6 | ||
Inner lower
| 17 | 8 | ||
Outer lower
| 32 | 11 | ||
Outer upper
| 96 | 41 | ||
Patterns of enhancement
| 179.854 | 0.000 | ||
Homogeneous
| 77(41.2%) | 5(7.4%) | ||
Heterogeneous
| 110(58.8%) | 11(16.2%) | ||
Peripheral
| 0(0%) | 52(76.5%) | ||
Difference of MVD (Edge - Center)
| 1.29 ± 5.03 | 15.60 ± 4.27 | -20.873 | 0.000 |
Histological grade
| 2.105 | 0.349 | ||
I
| 50 | 13 | ||
II
| 120 | 46 | ||
III
| 17 | 9 | ||
Cancer thrombosis
| 1.891 | 0.204 | ||
Negative
| 140 | 45 | ||
Positive
| 47 | 23 | ||
Nodal metastasis
| 0.174 | 0.777 | ||
Negative
| 88 | 30 | ||
Positive
| 99 | 38 | ||
Number of metastatic nodes
| 2.91 ± 5.97 | 6.21 ± 9.42 | -3.302 | 0.001 |
Clinical stage
| 18.458 | 0.002 | ||
I
| 46(24.6%) | 13(19.1%) | ||
IIA
| 60(32.1%) | 16(23.5%) | ||
IIB
| 64(34.2%) | 20(29.4%) | ||
IIIA
| 11(5.9%) | 7(10.3%) | ||
IIIB
| 2(1.1%) | 5(7.4%) | ||
IIIC
| 4(2.1%) | 7(10.3%) | ||
IV
| 0(0%) | 0(0%) | ||
ER
| 18.731 | 0.000 | ||
Negative
| 57(30.5%) | 41(60.3%) | ||
Positive
| 130(69.5%) | 27(39.7%) | ||
PgR
| 26.314 | 0.000 | ||
Negative
| 48(25.7%) | 41(60.3%) | ||
Positive
| 139(74.3%) | 27(39.7%) | ||
HER2
| 9.786 | 0.003 | ||
Negative
| 167(89.3%) | 50(73.5%) | ||
Positive
| 20(10.7%) | 18(26.5%) | ||
Ki67
| 10.827 | 0.001 | ||
Negative (<14%)
| 120(64.2%) | 28(41.2%) | ||
Positive (>14%)
| 67(35.8%) | 40(58.8%) | ||
P53 (%)
| 32.08 ± 31.58 | 29.90 ± 33.94 | 0.479 | 0.633 |
Clinicopathological subtypes
| 42.300 | 0.000 | ||
Luminal A
| 102(54.5%) | 17(25.0%) | ||
Luminal B (Ki67+)
| 44(23.5%) | 8(11.8%) | ||
Luminal B (HER2+)
| 14(7.5%) | 8(11.8%) | ||
HER2 overexpression
| 6(3.2%) | 10(14.7%) | ||
TNBC
| 21(11.2%) | 25(36.8%) | ||
Operation
| 0.819 | 0.485 | ||
Mastectomy
| 166 | 63 | ||
Tumorectomy
| 21 | 5 | ||
Chemotherapy program
| 17.357 | 0.004 | ||
Not performed
| 0(0%) | 2(2.9%) | ||
CMF
| 2(1.1%) | 0(0%) | ||
CAF or AC
| 60(32.1%) | 12(17.6%) | ||
CEF or EC
| 43(23.0%) | 19(27.9%) | ||
T or TC or TP
| 59(31.6%) | 17(25.0%) | ||
TAC or A-T
| 23(12.3%) | 18(26.5%) | ||
Radiotherapy
| 2.012 | 0.160 | ||
Not performed
| 104 | 31 | ||
Performed
| 83 | 37 | ||
Endocrine therapy
| 38.443 | 0.000 | ||
Not performed
| 27(14.4%) | 35(51.5%) | ||
TAM
| 99(52.9%) | 20(29.4%) | ||
LHRH
| 13(7.0%) | 5(7.4%) | ||
AI
| 48(25.7%) | 8(11.8%) | ||
Targeted therapy
| 0.116 | 1.000 | ||
Not performed
| 183 | 67 | ||
Performed
| 4 | 1 | ||
Overall survival
| 99.5% | 85.3% | 24.308 | 0.000 |
Event
| 1 | 10 | ||
Deaths
| 1 | 9 | ||
Lost to Follow-up
| 0 | 1 | ||
Median survival time
| 54.0 | 54.0 | 14.885 | 0.000 |
Disease-free survival
| 99.5% | 67.6% | 62.030 | 0.000 |
Event
| 1 | 22 | ||
Local recurrence
| 0 | 1 | ||
Contralateral breast cancer
| 0 | 4 | ||
Lung metastasis
| 0 | 2 | ||
Hepatic metastasis
| 0 | 5 | ||
Brain metastasis
| 0 | 3 | ||
Multi-organ
| 1 | 6 | ||
Lost to Follow-up
| 0 | 1 | ||
Disease-free survival
| 54.0 | 31.9 | 47.546 | 0.000 |
Follow-up time
| 0.384 | 0.701 | ||
Median
| 23.0 | 22.0 | ||
Range
| 12-58 | 12-59 |