Table 2.
Clinical studies on Cellular Residual Disease (CRD) detection in EBC patients
Abbreviations: breast cancer specific survival (BCSS); circulating tumor cells (CTCs) confidence interval (CI); distant disease-free survival (DDFS); disease free survival (DFS); distant metastasis free survival (DMFS); hazard ratio (HR); hormone receptor positive (HR+) local recurrence-free survival (LRFS); median time to recurrence (mTTR); not available (NA); prospective (Prosp); relapse free survival (RFS); retrospective (Retrosp.); time ratio (TR); triple negative breast cancer (TNBC).
| Author, year | Stage | Patient # | Subtype | Type of study | Timepoints | Detection method | Detection rate | Association with outcome | Observed association/lead time |
|---|---|---|---|---|---|---|---|---|---|
| SUCCESS A trial: - [42] - [43] |
I-III | 2026 | Various | Prosp. |
1) before adjuvant chemotherapy 2) after adjuvant chemotherapy (1492 patients) 3) 5 years after adjuvant chemotherapy (206 patients) |
CellSearch® |
1) 21.5% (435/2026); 19.6% of node-negative and 22.4% of node-positive Overall CTCs detected in 19% and 30% of patients with locoregional or distant relapse, respectively 2) 22.1% (330/1493) 3) 7.8% (16/206) |
1) DFS: HR,2.257; 95% CI 1.595-3.195; p < 0.0001 OS: HR, 2.447; 95% CI 1.491- 4.015; p = 0.0004 2) DFS HR, 1.124; 95% CI 1.02-1.25; p = 0.02 OS HR, 1.162; 95% CI 0.99- 1.37; p = 0.06 3) RFS in HR + BC: HR 5.14, 95% CI 1.47-18.03, p = 0.011 |
Patients with ≥5 CTCs: at 36 months, 28.1% of patients presented with recurrent disease and 14.3% had died |
| [44] | II-III | 547 | Various | Prosp. | Approximately 5 years after diagnosis | CellSearch® | 4,8% (26/547) | Risk of recurrence overall: HR 12.7, 95% CI 4.7-34.7, p < 0.001 Risk of recurrence HR+: HR 10.82, 95% CI 4.42-26.47, p < 0.001 |
mTTR: 2.8 years (range, 0.1-2.8 years) |
| [46] | I-II | 1697 NCDB and 1516 SUCCESS | Various | Prosp. | Before adjuvant therapy | CellSearch® | NCBD: 23.5% (399/1697) SUCCESS: 19.4% (294/1516) |
NCDB: CTC-negative patients had longer OS compared with CTC-positive patients (TR, 1.78; 95% CI, 1.34-2.36; p < 0.001) SUCCESS: CTC-negative status was independently associated with significantly longer DFS (TR, 2.18; 95% CI, 1.42-3.35; p < 0.001), LRFS (TR, 2.12; 95% CI, 1.21-3.72; p = 0.008), and OS (TR, 1.97; 95% CI, 1.20-3.23; p = 0.007) |
NA |
| van Dalum, 2014 | I-III | 403 | Various | Prosp. |
1) before surgery 2) 1 week after surgery 3) After completion of adjuvant chemo- and/or radiotherapy or before start endocrine therapy 4) 1-year post surgery 5) 2-years post surgery 6) 3-years after surgery |
CellSearch® |
1) 19% (75/403) 2) 18% (66/367) 3) 15% (40/263) 4) 12% (30/235) 5) 11% (18/144) 6) 13% (11/83) |
1) RFS p = 0.022; OS p = 0.006 2) RFS p = 0.852; OS p = 0.182 3) RFS p < 0.001; OS p = 0.018 4) RFS p = 0.006; OS p = 0.013 5) RFS p < 0.001; OS p = 0.045 6) RFS p = 0.439; OS p = 0.056 |
NA |
| [27] | I-III | 196 | TNBC | Prosp. | After surgery | Microchip system (combining immunomagnetics, high-flow rate fluidics, and size-based separation) | Arm A: 43% (21/49) Arm B: 39% (29/74) | DDFS (HR, 1.07; 95% CI, 1.01-1.13; p = 0.02), DFS (HR, 1.11; 95% CI, 1.03-1.19; p = 0.004), OS (HR, 1.09; 95% CI, 1.02-1.17; p = 0.01) |
NA |