Table 3 Summary of clinical studies analyzing ctDNA for MRD monitoring (ctDNA was analyzed retrospectively in those studies)
From: Use of ctDNA in early breast cancer: analytical validity and clinical potential
Reference (author and year) | Number of patients (N) and inclusion | Frequency of ctDNA analysis | Technique for ctDNA analysis | Median follow-up | Performance of ctDNA MRD monitoring |
|---|---|---|---|---|---|
Shaw et al.57 | N = 156 Completion of curative treatment in the previous 3 years and high risk of relapse (≥ 65% at 10 years) | Every 6 months for a total of 12 years | Tumor-informed SignateraTM | Not reported | Detect recurrence • Specificity 95% • Sensitivity 88% The median lead time of ctDNA-positivity before clinical relapse • 10.5 months Association with ctDNA-positivity • HR for RFS 47.5 • HR for OS 84.15 |
Lipsyc-Sharf et al.58 | N = 83 High-risk HR + HER2- more than 5 years after curative treatment | Every 6 to 12 months | Tumor-informed RaDaRTM | 2.0 years from the first sample | Detect recurrence • Sensitivity 85.7% • Specificity 97.4% The median lead time of ctDNA-positivity before clinical relapse • 12.4 months |
La Rocca,115 | N = 33 TNBC Stage II and more | Every 6 months (less than 50% of patients were followed) | Tumor-informed ddPCR | 5.1 years | Detect recurrence • Sensitivity 75% for distant disease in patients tested according to protocol • Specificity not reported |
Garcia-Murillas et al.116 | N = 144 All subtypes receiving NAT | Every 3 months for the first year, then every 6 months for a total of 5 years | Tumor-informed ddPCR | 36.3 months | Detect recurrence • Sensitivity 79% • Specificity not reported The median lead time of ctDNA-positivity before clinical relapse 10.7 months Association with ctDNA-positivity • HR for RFS 17.4 |
Janni et al.93 | N = 38 No information on subtypes | At 12 or 36 months post-diagnosis and/or at clinical relapse | Tumor-agnostic GuardantRevealTM | Not reported | Detect recurrence • Sensitivity 85% of distant and 15% of local relapses • Specificity 100% |
Janni et al.94 | N = 311 All subtypes | One timepoint at two years after the completion of adjuvant chemotherapy | Tumor-agnostic GuardantRevealTM | 65 months | Detect recurrence • Sensitivity 34% • Specificity 97.7% The median lead time of ctDNA-positivity before clinical relapse • 7.9 months Association with ctDNA-positivity • HR for RFS 11 |
Elliott et al.95 | N = 83 HER2- BC | Post-operative and every 3–6 months during follow-up | Tumor-agnostic Methylation analysis from GuardantINFINITYTM | 3.7 years | ctDNA detected post-operative and/or during follow-up • P = 0.00021 for association with clinical recurrence |
Loi et al.92 | N = 178 High-risk luminal BC | At trial entry and at 24 months | Tumor-informed SignateraTM | Unknown | 10/178 (5.6%) patients tested positive at baseline • 3 cleared ctDNA at 24 months: no relapse • 7 did not clear ctDNA at 24 months: all relapsed At 24 months 42/178 (23.6%) tested positive: all relapsed • Sensitivity for relapse 60% • Specificity for relapse 100% |
