Introduction
Patients and methods
Ethics statement
Patient population
Comparison of medical history risk factors, imaging features and clinicopathological characteristics between high vs low risk of 70-GS test
Comparisons of risk calculations from established models among patients with different categories of 70-GS risk
Establishment and validation of nomogram models to predict binary and quartile categorized risk of 70-GS
Statistical analysis
Results
Comparison of medical history risk factors, imaging features and clinicopathological characteristics between 70-GS high vs low risk patients
Clinicopathological and imaging characteristics | 70-gene high risk = N = 62 (%) | 70-gene low risk N = 88 (%) | P-value |
---|---|---|---|
70-gene score (Mean ± SD) | − 0.282 ± 0.234 | 0.226 ± 0.153 | < 0.001 |
Medical history factors | |||
Age (Mean ± SD) | 51.03 ± 9.67 | 52.27 ± 10.98 | 0.476 |
Age group | |||
< 40 | 8 (12.9) | 9 (10.2) | 0.705 |
40 ~ 49 | 21 (33.9) | 33 (37.5) | |
50 ~ 59 | 21 (33.9) | 24 (27.3) | |
≥ 60 | 12 (19.3) | 22 (25.0) | |
BMI (Mean ± SD) | 23.57 ± 3.17 | 23.49 ± 3.11 | 0.879 |
Childbirth (Mean ± SD) | 1.21 ± 0.70 | 1.16 ± 0.69 | 0.663 |
Age of menarche (Mean ± SD) | 13.95 ± 1.77 | 13.47 ± 1.36 | 0.059 |
Age of menopause (Mean ± SD) | 50.58 ± 2.99 | 50.34 ± 2.46 | 0.719* |
Family history of breast, ovarian and pancreatic cancer | |||
No | 58 (93.5) | 76 (86.4) | 0.189^ |
Yes | 4 (6.5) | 12 (13.6) | |
Cardiovascular disease as co-morbidity | |||
No | 54 (87.1) | 64 (72.7) | 0.034 |
Yes | 8 (12.9) | 24 (27.3) | |
Screen-detected NPBC | |||
No | 53 (85.5) | 73 (83.0) | 0.677 |
Yes | 9 (14.5) | 15 (17.0) | |
Bilateral cancer | |||
No | 60 (96.8) | 85 (96.6) | 0.945^ |
Yes | 2 (3.2) | 3 (3.4) | |
Imaging features | |||
MG BI-RADS density | |||
1 | 5 (8.1) | 9 (10.2) | 0.385# |
2 | 6 (9.7) | 17 (19.3) | |
3 | 34 (54.8) | 42 (47.7) | |
4 | 2 (3.2) | 5 (5.7) | |
Unknown | 15 (17.0) | 15 (24.2) | |
MG micro-calcification cluster | |||
No | 23 (37.1) | 44 (50.0) | 0.222# |
Yes | 24 (38.7) | 29 (33.0) | |
Unknown | 15 (24.2) | 15 (17.0) | |
MG nodule/mass | |||
No | 14 (22.6) | 26 (29.5) | 0.509# |
Yes | 33 (53.2) | 47 (53.4) | |
Unknown | 15 (24.2) | 15 (17.0) | |
MG lesion BI-RADS | |||
2, 3 and 4a | 12 (19.4) | 26 (29.5) | 0.274# |
4b and 4c | 23 (37.1) | 25 (28.4) | |
5 and 6 | 10 (16.1) | 18 (20.5) | |
Unknown | 17 (27.4) | 19 (21.6) | |
US lesion BI-RADS | |||
2, 3 and 4a | 4 (6.5) | 6 (6.8) | 0.340# |
4b and 4c | 35 (56.5) | 41 (46.6) | |
5 and 6 | 19 (30.6) | 30 (34.1) | |
Unknown | 4 (6.5) | 6 (6.8) | |
US max. diameter of tumor (Mean ± SD, cm) | 2.06 ± 0.73 | 2.10 ± 1.02 | 0.785# |
US min. diameter of tumor (Mean ± SD, cm) | 1.33 ± 0.46 | 1.24 ± 0.49 | 0.280# |
US diameter Ratio (min/max) (Mean ± SD) | 0.67 ± 0.15 | 0.64 ± 0.17 | 0.292# |
US aspect ratio | |||
Normal | 51 (82.3) | 68 (77.3) | 0.414# |
Abnormal | 7 (11.3) | 14 (15.9) | |
Unknown | 4 (6.5) | 6 (6.8) | |
US boundary | |||
Clear | 6 (9.7) | 8 (9.1) | 0.909# |
Unclear | 52 (83.9) | 74 (84.1) | |
Unknown | 4 (6.5) | 6 (6.8) | |
US morphology | |||
Regular | 3 (4.8) | 4 (4.5) | 0.941#^ |
Irregular | 55 (88.7) | 78 (88.6) | |
Unknown | 4 (6.5) | 6 (6.8) | |
US hyperechoicity | |||
No | 28 (45.2) | 37 (42.0) | 0.712# |
Yes | 30 (48.4) | 45 (51.1) | |
Unknown | 4 (6.5) | 6 (6.8) | |
US focality | |||
Unifocal | 41 (66.1) | 54 (61.4) | 0.546# |
Multifocal | 17 (27.4) | 28 (31.8) | |
Unknown | 4 (6.5) | 6 (6.8) | |
US blood flow | |||
Normal | 28 (45.2) | 45 (51.1) | 0.441# |
Abnormal | 30 (48.4) | 37 (42.0) | |
Unknown | 4 (6.5) | 6 (6.8) | |
US lymph node | |||
Normal | 49 (79.0) | 68 (77.3) | 0.807# |
Abnormal | 9 (14.5) | 14 (15.9) | |
Unknown | 4 (6.5) | 6 (6.8) | |
Clinicopathological characteristics | |||
Tumor histology | |||
IDC-NOS | 56 (90.3) | 83 (94.3) | 0.355 |
Other | 6 (9.7) | 5 (5.7) | |
pT | |||
T1 | 38 (61.3) | 60 (68.2) | 0.602^ |
T2 | 22 (35.5) | 26 (29.5) | |
T3 | 2 (3.2) | 2 (2.3) | |
Tumor volume (Mean ± SD, cm3) | 3.68 ± 5.46 | 3.97 ± 11.28 | 0.849 |
pN | |||
N0 | 35 (56.5) | 37 (42.10) | 0.082 |
N1 | 27 (43.5) | 51 (58.0) | |
Number of positive nodes | |||
0 | 35 (56.5) | 37 (42.0) | 0.371^ |
1 | 21 (33.9) | 37 (42.0) | |
2 | 5 (8.1) | 11 (12.5) | |
3 | 1 (1.6) | 3 (3.4) | |
TNM stage | |||
I | 35 (56.5) | 37 (42.0) | 0.082 |
II | 27 (43.5) | 51 (58.0) | |
Histological grade | |||
G1 | 2 (3.2) | 10 (11.4) | 0.006 |
G2 | 48 (77.4) | 74 (84.1) | |
G3 | 12 (19.4) | 4 (4.5) | |
LVI | |||
No | 53 (85.5) | 77 (87.5) | 0.721 |
Yes | 9 (14.5) | 11 (12.5) | |
ER positivity (%) (Mean ± SD) | 87.40 ± 11.20 | 87.70 ± 8.02 | 0.848 |
ER positive level | |||
Strong (3 +) | 44 (71.0) | 69 (78.4) | 0.298 |
Mild/Moderate (1–2 +) | 18 (29.0) | 19 (21.6) | |
PR positivity (%) (Mean ± SD) | 53.92 ± 36.49 | 68.83 ± 30.43 | 0.007 |
PR positive level | |||
High (≥ 20%) | 58 (93.5) | 84 (95.5) | 0.718^ |
Low (< 20%) | 4 (6.5) | 4 (4.5) | |
PR positive level | |||
Strong (3 +) | 37 (59.7) | 64 (72.7) | 0.199^ |
Moderate (2 +) | 20 (32.3) | 21 (23.9) | |
Mild (1 +) | 5 (8.1) | 3 (3.4) | |
Her2 | |||
0 | 15 (24.2) | 23 (26.1) | 0.845 |
1 + | 23 (37.1) | 35 (39.8) | |
2 + | 24 (38.7) | 30 (34.1) | |
Her2 FISH ratio (Mean ± SD) | 1.28 ± 0.38 | 1.22 ± 0.95 | 0.768$ |
Ki67 | |||
High (≥ 20%) | 54 (87.1) | 40 (45.5) | < 0.001 |
Low (< 20%) | 8 (12.9) | 48 (54.5) |
Comparisons of risk calculations from established models among patients with different categories of 70-GS risk
Risk calculated from established models | 70-gene high risk N = 62 (%) | 70-gene low risk N = 88(%) | P-value |
---|---|---|---|
AOL | |||
High | 46 (74.2) | 61 (69.3) | 0.516 |
Low | 16 (25.8) | 27 (30.7) | |
CTS5 | |||
Score (Mean ± SD) | 3.29 ± 0.58 | 3.14 ± 0.64 | 0.137 |
CTS5 | |||
High | 8 (12.9) | 12 (13.6) | 0.035 |
Intermediate | 33 (53.2) | 29 (33.0) | |
Low | 21 (33.9) | 47 (53.4) | |
IHC3 | |||
High | 27 (43.5) | 10 (11.4) | < 0.001 |
Low | 35 (56.5) | 78 (88.6) | |
NPI | |||
Score (Mean ± SD) | 4.58 ± 0.49 | 4.30 ± 0.52 | 0.001 |
NPI | |||
Poor | 0 (0.0) | 1 (1.1) | 0.348^ |
Moderate | 48 (77.4) | 60 (68.2) | |
Good | 14 (22.6) | 27 (30.7) |
Risk calculated from established models | 70-gene ultrahigh risk N = 12 (%) 4 | 70-gene high risk N = 50 (%) 3 | 70-gene low risk N = 65 (%) 2 | 70-gene ultralow risk N = 23 (%) 1 | P-value |
---|---|---|---|---|---|
AOL | 0.861& | ||||
High (1) | 9 (75.0) | 37 (74.0) | 44 (67.7) | 17 (73.9) | |
Low (0) | 3 (25.0) | 13 (26.0) | 21 (32.3) | 6 (26.1) | |
CTS5 | 0.162 | ||||
Score (Mean ± SD) | 3.34 ± 0.41 | 3.28 ± 0.62 | 3.14 ± 0.63 | 3.13 ± 0.66 | |
CTS5 | 0.250^ | ||||
High (2) | 1 (8.3) | 7 (14.0) | 9 (13.8) | 3 (13.0) | |
Intermediate (1) | 8 (66.7) | 25 (50.0) | 22 (33.8) | 7 (30.4) | |
Low (0) | 3 (25.0) | 18 (36.0) | 34 (52.3) | 13 (56.5) | |
IHC3 | < 0.001^ | ||||
High (1) | 10 (83.3) | 17 (34.0) | 10 (15.4) | 0 (0.0) | |
Low (0) | 2 (16.7) | 33 (66.0) | 55 (84.6) | 23 (100.0) | |
NPI | < 0.001 | ||||
Score (Mean ± SD) | 4.83 ± 0.58 | 4.52 ± 0.45 | 4.34 ± 0.46 | 4.18 ± 0.65 | |
NPI | 0.768^ | ||||
Poor (2) | 0 (0.0) | 1 (1.5) | 0 (0.0) | 0 (0.0) | |
Moderate (1) | 9 (75.0) | 39 (78.0) | 43 (66.2) | 17 (73.9) | |
Good (0) | 3 (25.0) | 11 (22.0) | 21 (32.3) | 6 (26.1) |
Establishment and validation of nomogram models to predict binary and quartile categorized risk of 70-GS
Nomogram models\Parameters to evaluate the nomograms | Binary | Quartile | ||
---|---|---|---|---|
Training set (N = 120) | Testing set (N = 30) | Training set (N = 120) | Testing set (N = 30) | |
AUC | 0.826 | 0.737 | 0.870 | 0.592 |
C-index (95% CI) | 0.903 (0.799–1.000) | 0.785 (0.700–0.870) | 0.854 (0.746–0.962) | 0.769 (0.703–0.835) |