Introduction
Materials and methods
Patients
Tissue microarrays and immunohistochemistry
Statistical analysis
Results
Patients' characteristics and survival
Characteristic | FEC (N= 546) | FEC-D (N= 553) | P-value |
---|---|---|---|
Age
| 0.794 | ||
<50 years | 261 (47.8%) | 260 (47.0%) | |
≥50 years | 285 (51.2%) | 293 (53.0%) | |
Menopausal status
| 0.770 | ||
Premenopausal | 332 (61.8%) | 331 (61.0%) | |
Postmenopausal | 214 (38.2%) | 222 (39.0%) | |
Surgery
| |||
Breast conservation | 313 (57.3%) | 342 (61.8%) | 0.127 |
Modified mastectomy | 233 (42.7%) | 211 (38.2%) | |
Pathological tumor size (pT)
| |||
<2 cm | 163 (32.2%) | 200 (39.9%) | 0.039 |
2 ≤pT <-5 cm | 306 (60.5%) | 269 (53.7%) | |
≥5 cm | 37 (7.3%) | 32 (6.4%) | |
SBR Grade
| |||
I | 52 (9.6%) | 67 (12.2%) | 0.288 |
II | 231 (42.6%) | 238 (43.2%) | |
III | 237 (43.7%) | 217 (39.4%) | |
Not gradable | 22 (4.1%) | 29 (5.3%) | |
Positive lymph nodes
| 329 (60.3%) | 342 (61.8%) | 0.589 |
1 to 3 | 217 (39.7%) | 211 (38.2%) | |
≥4 | |||
Hormone receptors
| |||
Positive (ER and/or PR) | 414 (78.0%) | 419 (78.0%) | 0.981 |
Negative (ER and PR) | 117 (22.0%) | 118 (22.0%) | |
Estrogen receptor
| |||
Positive | 394 (74.2%) | 391 (72.8%) | 0.607 |
Negative | 137 (25.8%) | 146 (27.2%) | |
Progesterone receptor
| |||
Positive | 276 (52.0%) | 305 (56.7%) | 0.122 |
Negative | 255 (48.0%) | 233 (43.3%) | |
HER2
| |||
Positive | 93 (17.1%) | 82 (15.0%) | 0.337 |
Negative | 451 (82.9%) | 466 (85.0%) | |
DFS, event
| |||
Yes | 150 (27%) | 118 (21%) | 0.021 |
No | 396 (73%) | 435 (79%) |
Protein markers, survival and docetaxel benefit
Marker | Category | N (%) | Univariate | Multivariate | ||
---|---|---|---|---|---|---|
Unadjusted Hazard Ratio (95%CI) | P-value (Log-rank) | Adjusted Hazard Ratio (95%CI) | P-value(Wald) | |||
AF6
| Neg. | 193 (23%) | ||||
Pos. | 656 (77%) | 0.86 (0.63 to 1.20) | 0.386 | 0.87 (0.61 to 1.24) | 0.437 | |
Angiogenin
| Neg. | 71 (7%) | ||||
Pos. | 879 (93%) | 1.06 (0.65 to 1.74) | 0.803 | 1.01 (0.59 to 1.75) | 0.967 | |
Aurora A
| Neg. | 585 68%) | ||||
Pos. | 276 (32%) | 1.41 (1.07 to 1.87) | 0.015 | 1.32 (0.98 to 1.79) | 0.070 | |
BCL2
| Neg. | 377 (39%) | ||||
Pos. | 580 (61%) | 0.60 (0.47 to 0.78) | <.001 | 0.82 (0.60 to 1.12) | 0.217 | |
α-Catenin
| Neg. | 359 42%) | ||||
Pos. | 501 (58%) | 0.88 (0.67 to 1.16) | 0.374 | 0.99 (0.73 to 1.34) | 0.927 | |
β-Catenin
| Neg. | 265 (29%) | ||||
Pos. | 636 (71%) | 0.83 (0.63 to 1.11) | 0.216 | 0.88 (0.64 to 1.21) | 0.439 | |
CAV1
| Neg. | 179 (19%) | ||||
Pos. | 778 (81%) | 1.39 (0.96 to 1.99) | 0.077 | 1.16 (0.76 to 1.76) | 0.495 | |
CD10
| Neg. | 409 (45%) | ||||
Pos. | 508 (55%) | 1.19 (0.91 to 1.55) | 0.199 | 1.20 (0.90 to 1.61) | 0.211 | |
CD44
| Neg. | 430 (61%) | ||||
Pos. | 280 (39%) | 0.83 (0.62 to 1.14) | 0.264 | 0.90 (0.65 to 1.25) | 0.524 | |
CK5/6
| Neg. | 248 (27%) | ||||
Pos. | 667 (73%) | 0.88 (0.67 to 1.18) | 0.414 | 0.98 (0.71 to 1.36) | 0.921 | |
CK8/18
| Neg. | 22 (2%) | ||||
Pos. | 948 (98%) | 0.30 (0.17 to 0.55) | <.001 | 0.54 (0.28 to 1.03) | 0.060 | |
CK14
| Neg. | 774 (83%) | ||||
Pos. | 158 (17%) | 1.01 (0.71 to 1.42) | 0.974 | 0.81 (0.55 to 1.19) | 0.288 | |
Cyclin D1
| Neg. | 316 (33%) | ||||
Pos. | 648 (67%) | 0.86 (0.66 to 1.13) | 0.301 | 1.11 (0.81 to 1.51) | 0.526 | |
E-Cadherin
| Neg. | 128 (13%) | ||||
Pos. | 873 (87%) | 1.09 (0.74-1.60) | 0.653 | 0.98 (0.62-1.57) | 0.937 | |
EGFR
| Neg. | 814 (81%) | ||||
Pos. | 185 (19%) | 1.02 (0.74 to 1.41) | 0.895 | 0.72 (0.49 to 1.05) | 0.090 | |
ER
| Neg. | 283 (26%) | ||||
Pos. | 785 (74%) | 0.53 (0.42 to 0.69) | <0.001 | 0.90 (0.47 to 1.71) | 0.744 | |
FGFR1
| Neg. | 114 (15%) | ||||
Pos. | 626 (85%) | 1.36 (0.86 to 2.14) | 0.189 | 1.60 (0.93 to 2.74) | 0.087 | |
FHIT
| Neg. | 237 (26%) | ||||
Pos. | 672(74%) | 1.03 (0.76 to 1.40) | 0.825 | 1.41 (0.98 to 2.01) | 0.062 | |
GATA3
| Neg. | 166 (17%) | ||||
Pos. | 816 (83%) | 0.70 (0.52 to 0.96) | 0.027 | 0.83 (0.58 to 1.19) | 0.311 | |
HER2
| Neg. | 917 (84%) | ||||
Pos. | 175 (16%) | 1.64 (1.23 to 2.19) | <0.001 | 1.12 (0.80 to 1.57) | 0.493 | |
Ki67
| Neg. | 661 (70%) | ||||
Pos. | 280 (30%) | 1.97 (1.51 to 2.56) | <0.001 | 1.53 (1.12 to 2.08) | 0.007 | |
MET
| Neg. | 602 (66%) | ||||
Pos. | 315 (34%) | 1.26 (0.97 to 1.65) | 0.088 | 1.25 (0.93 to 1.66) | 0.134 | |
Moesin
| Neg. | 824 (87%) | ||||
Pos. | 118 (13%) | 1.31 (0.91 to 1.89) | 0.145 | 1.95 (.63 to 1.44) | 0.815 | |
MUC1
| Neg. | 95 (9%) | ||||
Pos. | 938 (91%) | 0.59 (0.42 to 0.86) | 0.005 | 0.77 (0.51 to 1.16) | 0.213 | |
P21
| Neg. | 378 (41%) | ||||
Pos. | 545 (59%) | 0.93 (0.71 to 1.22) | 0.616 | 0.84 (0.62 to 1.13) | 0.241 | |
P27
| Neg. | 175 (19%) | ||||
Pos. | 768 (81%) | 0.89 (0.65 to 1.24) | 0.509 | 1.06 (0.75 to 1.50) | 0.754 | |
P53
| Neg. | 746 (75%) | ||||
Pos. | 246 (25%) | 1.59 (1.21 to 2.07) | <.001 | 1.29 (0.95 to 1.75) | 0.107 | |
P-Cadherin
| Neg. | 570 (61%) | ||||
Pos. | 371 (39%) | 1.44 (1.12 to 1.87) | 0.005 | 1.31 (0.96 to 1.78) | 0.089 | |
PR
| Neg. | 488 (46%) | ||||
Pos. | 581 (54%) | 0.54 (0.42 to 0.69) | <0.001 | 0.66 (0.47 to 0.92) | 0.013 | |
PTEN
| Neg. | 314 (34%) | ||||
Pos. | 610 (66%) | 1.00 (0.76 to 1.33) | 0.977 | 1.00 (0.74 to 1.36) | 0.991 | |
TACC2
| Neg. | 148 (17%) | ||||
Pos. | 723 (83%) | 1.05 (0.73 to 1.52) | 0.777 | 0.95 (0.64 to 1.42) | 0.796 | |
TACC3
| Neg. | 35 (6%) | ||||
Pos. | 564 (94%) | 1.83 (0.75 to 4.47) | 0.179 | 1.17 (0.47 to 2.88) | 0.738 | |
TAU
| Neg. | 685 (83%) | ||||
Pos. | 141 (17%) | 0.56 (0.36 to 0.88) | 0.011 | 0.75 (0.47 to 1.21) | 0.243 | |
TOPO2A
| Neg. | 199 (22%) | ||||
Pos. | 714 (78%) | 1.41 (0.99 to 2.00) | 0.052 | 1.39 (0.93 to 2.07) | 0.104 |
Marker | Category | N Arms A/B | Adjusted Hazard ratio (95% CI) | P-value forinteraction |
---|---|---|---|---|
AF6 | Neg. | 99/94 | 0.94 (0.50 to 1.79) | 0.663 |
Pos. | 321/335 | 0.86 (0.61 to 1.23) | ||
Angiogenin | Neg. | 34/37 | 1.68 (0.47 to 5.96) | 0.1 |
Pos. | 439/440 | 0.66 (0.49 to 0.89) | ||
Aurora A | Neg. | 293/292 | 0.91 (0.62 to 1.33) | 0.228 |
Pos. | 135/141 | 0.61 (0.38 to 1.00) | ||
BCL2 | Neg. | 184/193 | 0.78 (0.52 to 1.17) | 0.905 |
Pos. | 285/295 | 0.80 (0.54 to 1.19) | ||
α-Catenin | Neg. | 177/182 | 0.85 (0.53 to 1.37) | 0.875 |
Pos. | 250/251 | 0.79 (0.53 to 1.16) | ||
β-Catenin | Neg. | 123/142 | 1.19 (0.69 to 2.05) | 0.14 |
Pos. | 324/312 | 0.67 (0.47 to 0.96) | ||
CAV1 | Neg. | 82/97 | 1.11 (0.50 to 2.44) | 0.229 |
Pos. | 389/389 | 0.69 (0.51 to 0.94) | ||
CD10 | Neg. | 197/212 | 0.87 (0.55 to 1.38) | 0.741 |
Pos. | 259/249 | 0.77 (0.54 to 1.12) | ||
CD44 | Neg. | 210/220 | 0.63 (0.41 to 0.96) | 0.158 |
Pos. | 128/152 | 1.03 (0.61 to 1.73) | ||
CK5/6 | Neg. | 122/126 | 0.84 (0.48 to 1.48) | 0.96 |
Pos. | 332/335 | 0.79 (0.56 to 1.10) | ||
CK8/18 | Neg. | 13/9 | 4.73 (0.96 to 23.3) | 0.446 |
Pos. | 468/480 | 0.69 (0.52 to 0.91) | ||
CK14 | Neg. | 386/388 | 0.77 (0.56 to 1.05) | 0.142 |
Pos. | 84/74 | 0.41 (0.18 to 0.90) | ||
Cyclin D1 | Neg. | 161/155 | 0.78 (0.48 to 1.26) | 0.974 |
Pos. | 317/331 | 0.78 (0.55 to 1.10) | ||
E-Cadherin | Neg. | 62/66 | 1.77 (0.69 to 4.59) | 0.154 |
Pos. | 432/441 | 0.71 (0.53 to 0.95) | ||
EGFR | Neg. | 401/413 | 0.85 (0.63 to 1.16) | 0.235 |
Pos. | 95/90 | 0.58 (0.30 to 1.13) | ||
ER | Neg. | 137/146 | 0.79 (0.52 to 1.22) | 0.976 |
Pos. | 394/391 | 0.79 (0.56 to 1.10) | ||
FGFR1 | Neg. | 56/58 | 0.32 (0.10 to 1.02) | 0.178 |
Pos. | 306/320 | 0.84 (0.59 to 1.19) | ||
FHIT | Neg. | 127/110 | 0.00 (0.52 to 1.90) | 0.473 |
Pos. | 321/351 | 0.73 (0.52 to 1.01) | ||
GATA3 | Neg. | 88/78 | 0.74 (0.40 to 1.37) | 0.908 |
Pos. | 407/409 | 0.74 (0.54 to 1.02) | ||
HER2 | Neg. | 451/466 | 0.85 (0.63 to 1.15) | 0.367 |
Pos. | 93/82 | 0.65 (0.36 to 1.17) | ||
Ki67 | Neg. | 327/334 | 1.10 (0.75 to 1.61) | 0.012 |
Pos. | 147/133 | 0.51 (0.33 to 0.79) | ||
MET | Neg. | 301/301 | 0.91 (0.63 to 1.30) | 0.154 |
Pos. | 150/165 | 0.59 (0.38 to 0.94) | ||
Moesin | Neg. | 412/412 | 0.77 (0.57 to 1.05) | 0.92 |
Pos. | 56/62 | 0.80 (0.39 to 1.65) | ||
MUC1 | Neg. | 53/42 | 0.73 (0.32 to 1.70) | 0.651 |
Pos. | 461/477 | 0.73 (0.55 to 0.98) | ||
P21 | Neg. | 187/191 | 0.74 (0.48 to 1.14) | 0.879 |
Pos. | 272/273 | 0.76 (0.51 to 1.13) | ||
P27 | Neg. | 78/97 | 0.76 (0.41 to 1.42) | 0.826 |
Pos. | 378/390 | 0.73 (0.53 to 1.00) | ||
P53 | Neg. | 364/382 | 0.76 (0.54 to 1.08) | 0.74 |
Pos. | 123/123 | 0.71 (0.45 to 1.13) | ||
P-Cadherin | Neg. | 282/288 | 0.78 (0.52 to 1.17) | 0.622 |
Pos. | 179/192 | 0.68 (0.46 to 1.02) | ||
PR | Neg. | 255/233 | 0.86 (0.61 to 1.22) | 0.601 |
Pos. | 276/305 | 0.76 (0.50 to 1.15) | ||
PTEN | Neg. | 152/162 | 0.99 (0.60 to 1.64) | 0.221 |
Pos. | 315/295 | 0.68 (0.47 to 0.97) | ||
TACC2 | Neg. | 70/78 | 0.54 (0.25 to 1.20) | 0.397 |
Pos. | 366/357 | 0.87 (0.63 to 1.19) | ||
TACC3 | Neg. | 13/22 | 0.29 (0.04 to 2.14) | 0.363 |
Pos. | 284/280 | 0.97 (0.67 to 1.41) | ||
TAU | Neg. | 340/345 | 0.83 (0.59 to 1.16) | 0.611 |
Pos. | 65/76 | 0.96 (0.38 to 2.42) | ||
TOPO2A | Neg. | 104/95 | 0.82 (0.39 to 1.74) | 0.917 |
Pos. | 359/355 | 0.77 (0.56 to 1.06) |