Table 1 Study characteristics
Study | Study type | Phase | Total evaluable for ctDNA N= (TNBC n=) | Disease stage | ctDNA analysis method | ctDNA time points | Outcomes | Median follow-up |
|---|---|---|---|---|---|---|---|---|
Barnell 2022 [20] | Single arm, open label | II | 50 (50) | II-III | Personalized PCR panel (4–6 variants) based on tumor WES | Baseline, during NACT (C1D3), post-NACT (at surgery), every 6 m for 5 years, at relapse | Relationship of ctDNA to recurrence outcomes and pCR | Up to 48 months |
Butler 2019 [21] | Open label, multi-center adaptive randomized platform trial (I-SPY 2) | II | 10 (3) | II-III (cT1-4, N0-1) | DIDA unique molecular identifier sequencing based on tumor WES | Baseline, before every cycle of NACT, post-NACT (before surgery), after surgery, every 6 months after | Whether ctDNA levels and composition can predict response to treatment | Not specified |
Cailleux 2022 [22] | Prospective, translational | 44 (13) | cT1-4, cN0-1 | Personalized NGS (Signatera, up to 16 mutations) based on tumor WES | Baseline, post-NACT (before surgery), various unspecified follow-up times | EFS | 3.03 years (0.39–5.85 years) | |
Cavallone 2020 [13] | Prospective, observational | 26 (26) | II-III (cT0-4, N0-3) | Personalized PCR panel (average 5 variants) based on tumor WES | Baseline, during NACT (3 timepoints), post-NACT (before surgery), 10 patients drawn after surgery | RFS, OS | 63 months | |
Chen 2017 [23] | Open label, multi-site, randomized (BRE09-146) | II | 38 (38) | I-III | NGS (Ion Ampliseq Oncomine), matched tumor and plasma mutations | During adjuvant (C1 and C2 of adjuvant cisplatin + rucaparib, during maintenance (weeks 1 and 5 of maintenance rucaparib) | DFS | 24 months |
Chen 2020 [24] | Observational | 36 (36) | Early and metastatic | NGS (Roche Avenio), unclear if tumor informed | First day of adjuvant intervention | DFS, lead time interval | Not specified | |
Gupta 2023 [25] | Single arm, open label | II | 29 (29) | I-III | Personalized NGS (Signatera, up to 16 mutations) based on tumor WES | Before, during, and after adjuvant capecitabine | ctDNA detection and correlation with tumor genomics, RFS, OS | 19.3 months (10.7–43.7) |
Lee 2023 [26] | Prospective, observational | 11 (11) | cT2-3, N2-3 | NGS, non-tumor informed | Before radiation, 3 weeks after radiation, and 1 month after radiation | DFS | 48 months | |
Lin 2021 [27] | Prospective, observational | 95 (25) | II-III | NGS, non-tumor informed | Baseline, post-NACT (after surgery) | RFS | 5.1 years | |
Magbanua 2023 [12] | Open label, multi-center adaptive randomized platform trial (I-SPY 2) | II | 283 (138) | II-III (cT1-4, N+/-) | Personalized NGS (Signatera, up to 16 mutations) based on tumor WES | Baseline, during NACT (at 3 weeks and 12 weeks), post-NACT (before surgery) | pCR, DRFS | 3.12 years (0.31–7.91) |
Molinero 2022 [28] | International, multicenter, open label, 2 arm | III | 186 (186) | “early”, stage not specified | Personalized assays (up to 16 SNVs) based on tumor WES | After surgery before ACT, post-ACT | IDFS, OS | Not specified |
Ortolan 2021 [29] | Prospective, observational | 31 (31) | II-III (cT2-4, N+/-) | Personalized PCR assay (1 mutation) based on tumor NGS | Baseline, during NACT, after NACT (before surgery), after surgery | EFS | 3 years (0.5–6.5) | |
Parsons 2023 [30] | Case-control subset of a prospective, randomized trial (TBCRC 030) | II | 42 (42) | cT1-3, N+/- | ctDNA assays (up to 1000 mutations per patient) based on tumor WGS | Baseline, 3 weeks into NACT, at 12 weeks of NACT (before surgery) | ctDNA dynamics in relation to tumor response and disease recurrence | Not specified |
Radovich 2020 [31] | Multicenter, randomized control trial (BRE12-158) | II | 142 (142) | I-III | NGS (Foundation), non-tumor informed | Before ACT (after surgery and radiation) | DDFS | 17.2 months (0.1–58.3 months) |
Roseshter 2023 [32] | Prospective, observational | 34 (34) | Not specified | Personalized PCR assay (5 mutations) based on tumor WES | Post-NACT (before surgery), after surgery, 3 months (during ACT), 6 months (after ACT) | RFS | Not specified | |
Schneider 2022 [33] | Multicenter, randomized control trial (BRE12-158) | II | 146 (146) | I-III | NGS (Foundation), non-tumor informed | T0 = after surgery, before adjuvant treatment | DDFS, DFS, OS | 34.2 months |
Shaw 2024 [34] | Multicenter, prospective, observational | 153 (23) | I-III | Personalized NGS (Signatera, up to 16 mutations) based on tumor WES | Every 6 months for up to 4 years in patients that completed therapy in the past 3 years | RFS, OS | 58 months (8–99) | |
Stecklein 2023 [35] | Multicenter, prospective, observational | 80 (80) | I-III | NGS, non-tumor informed | 1–6 months after all treatment (local and systemic) | EFS | 31 months | |
Turner 2023 [36] | Multicenter, prospective clinical trial (c-TRAK) | II | 161 (161) | II-III | Personalized PCR (1–2 mutations) based on tumor NGS | After all treatment, then every 3 months for 24 months | ctDNA detection and clearance rate | 20.4 months |
Zaikova 2024 [37] | Prospective, observational | 130 (130) | cT1-4, N+/- | NGS, non-tumor informed | Within 7 months after completion of all therapy | RFS | 25 months (1–53) |