Background
Methods
Patients' selection
Gene expression data analysis
Statistical analysis
Results
Identification of a prognostic kinase expression signature
Characteristics (N) | Basal |
---|---|
N = 591 | |
N (% of evaluated cases) | |
Age (445) | |
≤ 50 years | 215 (57%) |
> 50 years | 162 (43%) |
Histological type (256) | |
ductal | 234 (91%) |
lobular | 7 (3%) |
other* | 15 (6%) |
Pathological tumor size, pT (466) | |
pT1 | 115 (25%) |
pT2-4 | 351 (75%) |
Pathological lymph node status, pN (493) | |
negative | 314 (64%) |
positive | 179 (36%) |
Tumor grade (493) | |
SBR 1 | 14 (3%) |
SBR 2-3 | 479 (97%) |
IHC ER status (507) | |
negative | 411 (81%) |
positive | 96 (19%) |
IHC PR status (223) | |
negative | 199 (89%) |
positive | 24 (11%) |
IHC ERBB2 status (105) | |
negative | 86 (84%) |
positive | 19 (16%) |
Adjuvant chemotherapy (309) | |
no | 203 (66%) |
yes | 106 (34%) |
Adjuvant hormone therapy (322) | |
no | 237 (95%) |
yes | 13 (5%) |
Events (453)** | 183 (40%) |
5-year DFS (453)** | 61% |
Univariate Analysis | Multivariate Analysis | |||||
---|---|---|---|---|---|---|
N | HR [95% CI] | p -value | N | HR [95% CI] | p -value | |
Age ≤50 (vs > 50 y)
| 73 | 1.83 [0.79-4.26] | 0.16 | |||
pT > 20 mm (vs ≤ 20 mm)
| 73 | 1 [0.96-1.05] | 0.95 | |||
pN pos (vs neg)
| 73 | 1.93 [0.88-4.24] | 0.1 | |||
Grd 2-3 (vs 1)*
| 73 | 0.15 [0.02-1.18] | 0.07 | |||
ER pos (vs neg)
| 73 | 1.08 [0.25-4.68] | 0.91 | |||
Vascular invasion
| 72 | 2.32 [1.04-5.18] |
0.04
| 72 | 2.30 [1.03-5.14] |
0.04
|
Lymphocyte infiltrate **
| 71 | 0.38 [0.11-1.28] | 0.12 | |||
Chemotherapy
| 73 | 0.62 [0.18-2.12] | 0.62 | |||
Hormone therapy
| 72 | 1.76 [0.64-4.81] | 0.27 | |||
Immune metagene High (vs Low)
| 73 | 0.21 [0.06-0.70] |
0.01
| 72 | 0.22 [0.07-0.73] |
0.01
|
Validation of the prognostic signature
Characteristics (N) | Immune-High n = 122 | Immune-Low n = 396 | p-value | OR (95%CI) |
---|---|---|---|---|
N (% of evaluated cases) | ||||
Age (372) | 0.71* | |||
≤ 50 years | 53 (62%) | 169 (59%) | 1 | |
> 50 years | 33 (38%) | 117 (41%) | 1.11 (0.66-1.89) | |
Pathological tumor size, pT (394) | 0.11* | |||
pT1 | 32 (33%) | 73 (24%) | 1 | |
pT2-4 | 64 (67%) | 225 (76%) | 1.54 (0.9-2.6) | |
Pathological lymph node status, pN (420) | 0.90* | |||
negative | 62 (65%) | 208 (64%) | 1 | |
positive | 33 (35%) | 117 (36%) | 1.06 (0.64-1.77) | |
Tumor grade (420) | ND | |||
SBR 1 | 0 (0%) | 13 (4%) | ||
SBR 2-3 | 103 (100%) | 304 (96%) | ||
IHC ER status (434) | 0.57* | |||
negative | 73 (77%) | 269 (79%) | 1 | |
positive | 22 (23%) | 70 (21%) | 0.86 (0.49-1.57) | |
Lymphocyte infiltrate (56) | 0.51* | |||
absent | 6 (46%) | 14 (33%) | 1 | |
present | 7 (54%) | 29 (67%) | 1.76 (0.41-7.48) | |
Adjuvant chemotherapy (354) | 0.43* | |||
no | 49 (64%) | 162 (58%) | 1 | |
yes | 28 (36%) | 115 (42%) | 1.24 (0.72-2.18) | |
Adjuvant hormone therapy (269) | 0.11* | |||
no | 59 (91%) | 197 (97%) | 1 | |
yes | 6 (9%) | 7 (3%) | 0.40 (0.12-1.46) | |
Follow-up (months, median) (380) | 95 | 89 | 0.44** | |
Relapses (380) | 25 (26.3%) | 133 (46.7%) | 4.77 E-04* | 0.41 (0.23-0.70) |
5-year DFS (380) | 78% | 54% | 1.6 E-04*** |
Univariate Analysis | Multivariate Analysis* | |||||||
---|---|---|---|---|---|---|---|---|
N | HR [95%CI] | p -value | N | HR [95%CI] | p -value | HR [95%CI] | p -value | |
Age ≤ 50 (
vs
> 50y)
| 253 | 0.96 [0.65-1.41] | 0.84 | |||||
pT > 20 mm (
vs
≤ 20 mm)
| 275 | 1.40 [0.93-2.11] | 0.11 | |||||
pN pos (
vs
neg)
| 301 | 1.53 [1.04-2.25] | 0.032 | 301 | 1.58 [1.07-2.33] | 0.021 | 1.46 [0.99-2.16] | 0.06 |
Grd 2-3 (
vs
1)
| 302 | 3.00 [0.74-12.1] | 0.12 | |||||
ER pos (
vs
neg)
| 315 | 0.68 [0.45-1.03] | 0.07 | |||||
Chemotherapy
| 236 | 1.28 [0.77-2.14] | 0.34 | |||||
Hormone therapy
| 250 | 1.01 [0.41-2.48] | 0.98 | |||||
MBC-based classifier
| 380 | 0.59 [0.43-0.82] | 1.72 E-04 | 301 | 0.59 [0.40-0.87] | 7.5 E-03 | ||
Immune metagene High (
vs
Low)
| 380 | 0.45 [0.29-0.69] | 2.4 E04 | 301 | 2.15 [1.32-3.50] | 0.0022 | 0.54 [0.33-0.89] | 0.015 |
Comparison with existing classifiers
N | HR [IC95] | p-value | ||
---|---|---|---|---|
Immune-metagene
| High vs Low | 380 | 2.23 [1.45-3.42] | 2.4 E-04 |
70-gene signature
| Poor vs Good | 380 | 1 [1] | NaN* |
Genomic grade index
| High vs Low | 380 | 1.30 [0.53-3.18] | 0.56 |
76-gene signature
| Poor vs Good | 317 | 1.40 [0.96-2.03] | 0.08 |