Table 4.
ctDNA in metastatic breast cancer.
| Authors [Reference] | Study Design | Method | Findings |
|---|---|---|---|
| Tan, G., et al., 2018 [69] | Meta-analysis of 10 different studies | n = 1127. There was a strong association between cfDNA and OS, DFS, and RFS. Subgroup analyses confirmed the role of cfDNA as a strong prognostic marker regardless of cfDNA analyses, sampling time, sample source, detection method, tumor stage, sample size, or area. | |
| Shaw, J.A., et al., 2017 [70] | Comparison of cfDNA profiles to isolated CTCs | NGS and ddPCR | n = 5. Total cfDNA levels were significantly associated with OS. In all 5 patients, cfDNA profiles matched the mutations found in matched, isolated CTCs (apart from two additional mutations that may have been acquired with disease progression). |
| Fernandez-Garcia, D., et al., 2019 [71] | ctDNA with CTCs | qPCR | n = 94. Level of total cfDNA is a strong predictor of OS, PFS, and disease relapse (when comparing responders to non-responders). Combining CTC and cfDNA levels is a stronger biomarker for OS than the combination of CA15-3 and AP. |
| Murtaza, M., et al., 2015 [72] | cfDNA throughout treatment plan to evaluate clonal evolution | ddPCR and Whole Exome Sequencing | n = 1. Changes in serial collections of cfDNA throughout treatment correlate with different treatment responses between sites of metastatic disease, allowing cfDNA to provide real-time information of multifocal clonal evolution. |
| Darrigues, L., et al., 2021 [75] | cfDNA before, during, after treatment and at disease progression | ddPCR | n = 61. Serial analyses of cfDNA is an effective tool to measure treatment response to palbociclib and fulvestrant in ER+ metastatic breast cancer. Early variations in levels of cfDNA is a prognostic factor of PFS. |
| Fabrice Andre, F.S., et al., 2020 [76] | ctDNA at baseline | NGS | n = 1053. Genetic alterations from ctDNA can serve as potential biomarkers of response or resistance in metastatic breast cancer. |
| Hrebien, S., et al., 2019 [77] | ctDNA levels at baseline and early treatment | ddCPR | n = 59. Early changes in ctDNA dynamics were a strong indicator for PFS |
| Turner, N.C., et al., 2020 [78] | ctDNA before treatment | ddPCR and targeted sequencing | n = 1034. Concordance between ddPCR and targeted sequencing of ctDNA was 96–99%, and sensitivity of ddPCR ctDNA mutations identified in tissue sequencing was 98%. Three of the four treatment arms met or exceeded target response rate, demonstrating that ctDNA testing offers accurate and rapid genotyping that can allow the selection of mutation-directed treatments for metastatic breast cancer patients. |
cfDNA, cell-free DNA; CTC, circulating tumor cell; ctDNA, circulating tumor DNA; ddPCR, digital drop polymerase chain reaction; DFS, disease-free survival; NGS, next-generation sequencing; OS, overall survival; TNBC, triple-negative breast cancer.