Table 1. Patient demographics and clinicopathological parameters in the entire cohort and broken down into pre- and post-trastuzumab era trials.
| Trial | ||||
|---|---|---|---|---|
| Entire population | Pre-trastuzumab era trials (HE10/97 and ΗΕ10/00) | Post-trastuzumab era trials (ΗΕ10/05 and HE10/08) | p-value* | |
| Patients | ||||
| N | 1766 | 620 | 1.146 | |
| Age (years) | ||||
| Mean (SD) | 53.2 (11.5) | 52.8 (11.2) | 53.4 (11.7) | 0.31 |
| Median | 52.9 | 52.4 | 53.3 | |
| Min-Max | 21-83 | 22-79 | 21-83 | |
| Tumor size in cm | ||||
| Mean (SD) | 2.9 (1.6) | 3.3 (1.8) | 2.7 (1.5) | < 0.001 |
| Median | 2.5 | 3 | 2.4 | |
| Min-Max | 0–15 | 0–15 | 0–11 | |
| Positive lymph nodes (N) | ||||
| Mean (SD) | 4.8 (6.4) | 6.8 (6.9) | 3.7 (5.9) | < 0.001 |
| Median | 2 | 4 | 2 | |
| Min-Max | 0–54 | 0–43 | 0–54 | |
| Ki67 (% of positive cells) | ||||
| Mean (SD) | 30.2 (26.7) | 31.4 (23.7) | 29.4 (28.3) | < 0.001 |
| Median | 20 | 25 | 19.5 | |
| Min-Max | 0–100 | 0–98 | 0–100 | |
| CEN17 copies (N) | ||||
| Mean (SD) | 2.4 (1.4) | 2.6 (1.9) | 2.3 (1.0) | 0.007 |
| Median | 2 | 2.1 | 2 | |
| Min-Max | 1–18 | 1–18 | 1–11 | |
| N (%) | N (%) | N (%) | ||
| Age (N = 1764) | ||||
| ≤ 50 years | 724 (41.0) | 270 (43.5) | 454 (39.7) | 0.12 |
| > 50 years | 1040 (59.0) | 350 (56.5) | 690 (60.3) | |
| Menopausal status (N = 1764) | ||||
| Postmenopausal | 952 (54.0) | 325 (52.4) | 627 (54.8) | 0.34 |
| Premenopausal | 812 (46.0) | 295 (47.6) | 517 (45.2) | |
| Tumor size (N = 1763) | ||||
| ≤ 2 cm | 639 (36.2) | 174 (28.1) | 465 (40.6) | < 0.001 |
| > 2 cm | 1124 (63.8) | 445 (71.9) | 679 (59.4) | |
| Positive lymph nodes (N = 1764) | ||||
| 0–3 | 1057 (59.9) | 253 (40.8) | 804 (70.3) | < 0.001 |
| ≥ 4 | 707 (40.1) | 367 (59.2) | 340 (29.7) | |
| Histological grade (N = 1757) | ||||
| I | 113 (6.4) | 29 (4.7) | 84 (7.4) | 0.083 |
| II | 792 (45.1) | 282 (45.5) | 510 (44.9) | |
| III-Undifferentiated | 852 (48.5) | 309 (49.8) | 543 (47.8) | |
| Histological type (N = 1764) | ||||
| IC-NST | 1442 (81.7) | 472 (76.1) | 970 (84.8) | < 0.001 |
| Invasive lobular | 157 (8.9) | 60 (9.7) | 97 (8.5) | |
| Mixed | 83 (4.6) | 48 (7.7) | 35 (3.1) | |
| Other | 82 (4.6) | 40 (6.5) | 42 (3.7) | |
| Surgery (binary) (N = 1764) | ||||
| MRM | 1009 (57.2) | 428 (69.0) | 581 (50.8) | < 0.001 |
| Other | 755 (42.8) | 192 (31.0) | 563 (49.2) | |
| Hormonotherapy (N = 1759) | ||||
| No | 403 (22.9) | 121 (19.6) | 282 (24.7) | 0.017 |
| Yes | 1356 (77.1) | 495 (80.4) | 861 (75.3) | |
| Radiotherapy (N= 1716) | ||||
| No | 414 (24.1) | 128 (21.4) | 286 (25.6) | 0.058 |
| Yes | 1302 (75.9) | 469 (78.6) | 833 (72.4) | |
| Subtypes entire cohort (N = 1765) | ||||
| Luminal A | 588 (33.3) | 148 (23.9) | 440 (38.4) | < 0.001 |
| Luminal B | 463 (26.2) | 179 (28.9) | 284 (24.8) | |
| Luminal-HER2 | 318 (18.0) | 142 (23.9) | 176 (15.4) | |
| HER2-Enriched | 161 (9.1) | 59 (9.5) | 102 (8.9) | |
| TNBC | 235 (13.3) | 92 (14.8) | 143 (12.5) | |
| Subtypes entire cohort combined (N = 1765) | ||||
| Luminal A/B | 1051 (59.6) | 327 (52.8) | 724 (63.2) | <0.001 |
| HER2-positive | 235 (13.3) | 92 (14.8) | 143 (12.5) | |
| TNBC | 479 (27.1) | 201 (32.4) | 278 (24.3) | |
| Subtypes concordant (N = 1248) | ||||
| Luminal A | 506 (40.5) | 121 (31.5) | 385 (44.6) | < 0.001 |
| Luminal B | 388 (31.1) | 141 (36.7) | 247 (28.6) | |
| Luminal-HER2 | 150 (12.0) | 55 (14.3) | 95 (11.0) | |
| HER2-Enriched | 91 (7.3) | 32 (8.3) | 59 (6.8) | |
| TNBC | 113 (9.1) | 35 (9.1) | 78 (9.0) | |
| Subtypes concordant combined (N = 1248) | ||||
| Luminal A/B | 894 (71.6) | 262 (68.2) | 632 (73.1) | 0.13 |
| HER2-positive | 241 (19.3) | 87 (22.7) | 154 (17.8) | |
| TNBC | 113 (9.1) | 35 (9.1) | 78 (9.0) | |
| ER/PgR central (N = 1697) | ||||
| Negative | 312 (18.4) | 115 (19.6) | 197 (17.8) | 0.36 |
| Positive | 1385 (81.6) | 473 (80.4) | 912 (82.2) | |
| ER/PgR local (N= 1761) | ||||
| Negative | 399 (22.7) | 151 (24.4) | 248 (21.7) | 0.19 |
| Positive | 1362 (77.3) | 467 (75.6) | 895 (78.3) | |
| HER2 IHC central (N = 1692) | ||||
| No overexpression | 1459 (86.2) | 502 (84.5) | 957 (87.2) | 0.13 |
| Overexpression | 233 (13.8) | 92 (15.5) | 141 (12.8) | |
| HER2 IHC local (N = 1729) | ||||
| No overexpression | 1256 (72.6) | 396 (67.1) | 860 (75.5) | < 0.001 |
| Overexpression | 473 (27.4) | 194 (32.9) | 279 (24.5) | |
| HER2 status central (N = 1707) | ||||
| Negative | 1305 (76.4) | 444 (74.1) | 861 (77.7) | 0.096 |
| Positive | 402 (23.6) | 155 (25.9) | 247 (22.3) | |
| CK5 central (N= 1689) | ||||
| Negative | 1452 (86.0) | 523 (89.7) | 929 (84.0) | 0.001 |
| Positive | 237 (14.0) | 60 (10.3) | 177 (16.0) | |
| EGFR central (N = 1690) | ||||
| Negative | 1404 (83.1) | 487 (83.4) | 917 (82.9) | 0.80 |
| Positive | 286 (16.9) | 97 (16.6) | 189 (17.1) | |
| Basal (N = 1683) | ||||
| Basal | 368 (21.9) | 106 (18.2) | 262 (23.8) | 0.009 |
| Non-Basal | 1315 (78.1) | 475 (81.8) | 840 (76.2) | |
| RandomGroup | ||||
| E-CMF | 86 (4.8) | 86 (13.8) | 0 (0.0) | < 0.001 |
| E-CMF-Doc | 182 (10.4) | 0 (0.0) | 182 (15.8) | |
| E-CMF-T | 199 (11.2) | 0 (0.0) | 199 (17.4) | |
| E-T-CMF | 1059 (60.0) | 294 (47.4) | 765 (66.8) | |
| ET-CMF | 240 (13.6) | 240 (38.8) | 0 (0.0) | |
| Survival data | ||||
| Median FU in months | 72.5 | 118.4 | 65.6 | |
| N of valid cases | 1764 | 620 | 1144 | < 0.001 |
| Deaths (N) | 278 | 181 | 97 | |
| Event-free at 3 years | 95.4 | 93.8 | 96.2 | |
| Event-free at 5 years | 89.3 | 85.2 | 91.7 | |
| Relapses (N) | 389 | 225 | 164 | < 0.001 |
| Event-free at 3 years | 88.0 | 82.8 | 90.9 | |
| Event-free at 5 years | 82.2 | 74.5 | 86.5 | |
All patients had informative NGS data.
Notes: MRM: modified radical mastectomy; FU: follow-up; N: number; IC-NST: invasive carcinoma of non-specific type; IHC: immunohistochemistry.
*
Comparison of variable categories in the pre- and post- trastuzumab era series.