Table 1.
CTC-targeting strategies for breast cancer prognosis.
| Epithelial(E)-CTC measurement through Ep-CAM-based systems | |||||||||
| Study Design | Study Population | Patients | Patients Positive for CTCs (%) | CTC Cut-Off | Overall Survival | Progression-Free Survival | Disease-Free Survival | Notes | Ref. |
| Prospective multicentric study | Metastatic breast cancer | 177 | 87 (49%) | ≥5 CTCs/ 7.5 mL of PB | >18 months CTC-negative group vs. 10.1 months CTC positive group p < 0.001 | 7.0 months CTC negative vs. 2.7 months CTC positive, p < 0.001 | N.R. | First validation study which established the positive-threshold value for the CTC count | [30] |
| Retrospective multicentric study | Metastatic breast cancer | 1944 (911 positive for CTCs) | 911 (46.9%) | ≥5 CTCs/ 7.5 mL of PB | HR 2.78 for CTC-positive group (95% CI 2.42–3.19, p < 0.001) | HR 1.92 for CTC-positive group (95% CI 1.73–2.14, p < 0.0001) | N.R. | A positive CTC-count had a significant prognostic value also at 3-5 weeks after the baseline count and at 6-8 week after the first treatment dose. CTC count improved the predictive value of the full clinicopathological prognostic model | [31] |
| Retrospective multicentric study | Non-metastatic breast cancer (Stage I to III) | 3173 | 640 (20.2%) | ≥1 CTC/ 7.5 mL of PB | HR 1.97 for CTC-positive group (95% CI, 1.51 to 2.59 p < 0.001) | N.R. | HR, 1.82 for CTC-positive group (95% CI), 1.47 to 2.26 | In non-metastatic breast cancer patients, CTC count was confirmed as an independent prognostic factor | [32] |
| Meta-analysis | Stage I to IV breast cancer | 550 | N.A. | ≥1 HER2/neu positive CTC/ 7.5 mL of PB | In patients without metastasis, Her2-positive CTCs associated with HR 2.273 (95% CI: 1.340–3.853, p = 0.002) | In patients without metastasis, HER2/neu-positive CTCs associated with HR = 2.870 (95% CI: 1.298–6.343, p = 0.009) | N.R. | HER2/neu-positive CTCs were associated with worse OS and PFS in non-metastatic patients only (non-significant in metastatic patients). This was independent from the HER2/neu status of the primitive tumor | [42] |
| Non-Ep-CAM-based systems (measuring both epithelial (E)-CTCs, biphenotypic epithelial/mesenchymal (EM)-CTCs, and mesenchymal (M)-CTCs | |||||||||
| Study Design | Study Population | Patients | Patients Positive for CTCs (%) | CTC Cut-Off | Overall Survival | Progression-Free Survival | Disease-Free Survival | Notes | Ref. |
| Prospective observational study | Metastatic breast cancer | 56 | 47 (83%) | N.A. | HR 1.035 for EM-CTC positive patients (95% CI, 1.013 to 1.057 p = 0.0016) HR 1.019 for E-CTC positive patients (95% CI, 1.004 to 1.034 p = 0.0013) | HR 1.021 for EM-CTC positive patients (95% CI 1.004–1.039 p = 0.016) | N.R. | Different sub-populations of CTCs were evaluated. Expression of both epithelial and mesenchymal markers was associated to a reduced OS and PFS. CTCs negative for both epithelial and mesenchymal markers were associated with CNS metastases | [53] |
| Prospective, randomized, open-labeled phase III study | HER2-negative metastatic breast cancer | 108 | 90 (83.3%) | CTCs ≥ 10/ 5 mL PB with a proportion of M-CTCs > 10.7% | N.R. | 6.2 months for patients with ≥ 10 CTCs and with a proportion of M-CTCs > 10.7% vs. 9.9 months for the other groups (p = 0.010) | Non-significant | Validation study for the CanPatrol CTC enrichment technique. All the three sub-populations of CTCs were evaluated. The follow-up was of 12 months | [54] |
Abbreviations: Ref.—References; CTC(s)—circulating tumor cell(s); PB—peripheral blood; HR—hazard ratio; N.R.—Not Reported; N.A.—Not Applicable.