Table 3.

Clinical trials of breast ctDNA-based ctDNA-based MRD detection

Trial registration	Study Status	Design	Study type	Intervention/observational model	Country	Pt number	ctDNA detection method	Study outcomes	Refs.
NCT04920708	Recruiting	Randomized	Interventional	Parallel Assignment	UK	324	–	Assessing the progression-free survival (PFS) in advanced ER + /HER2- BC patients carrying identifiable mutations and exhibiting high levels of ctDNA after two weeks of CDK4/6 inhibitor/fulvestrant treatment, aiming to contrast the PFS among those randomly assigned to receive palbociclib/fulvestrant/ipatasertib with those receiving the standard palbociclib-fulvestrant treatment	[147]
NCT05858242	Recruiting	–	Observational	Cohort	China	1000–1050	plasma ctDNA polygene methylation test	• Identifying the ctDNA methylation targets that are specific to BC • Examine the use of postoperative ctDNA methylation in assessing the prognostic value of BC surgery and subsequent surveillance	[148]
NCT06087120	Recruiting	–	Observational	Cohort	Vietnam	–	PCR based techniques	determine the prevalence and evolution of ctDNA in cancer patients' blood samples before, during, and following neoadjuvant therapy Examining how pCR response in neo-adjuvant therapy relates to ctDNA expression on MRI imaging	[149]
NCT03079011	Active, not recruiting	Randomized	Interventional	Sequential Assignment	France	1017	–	• Incidence of adverse events that arise during treatment • Both progression-free and chemotherapy-free survival are possible	[150]
NCT05333874	Active, not recruiting	Nonrandomized	Interventional pilot study	Single Group Assignment	United States	34	PCR based techniques	Levels of Detectable ctDNA	[151]
NCT04308720	Recruiting	–	Observational	Cohort	United States	400	–	• Variations in the mutational burden and ctDNA detection rate in BC patients who show indications of regional nodal irradiation • The alteration in the percentage of patients exhibiting detectable ctDNA after treatment and three months afterward in comparison to the initial measurement • The relationship between detectable ctDNA at each specific time point and the survival period without recurrence or invasion	[152]
NCT05945290	Recruiting	–	Observational	Cohort	United States	120	TARgeted DIgital Sequencing (TARDIS) and Quality Assessment (QA) assay	Variation in the levels of tumor-specific circulating tumor DNA (ctDNA)	[153]
NCT05770531	Recruiting	Randomized	Interventional	Parallel Assignment	United States	120	–	PFS and OS	[154]
NCT04354064	Recruiting	–	Observational	Cohort	United States	3362	–	Freedom from progression and Overall survival (OS)	[155]
NCT04872608	Withdrawn	N/A	Interventional	Single Group Assignment	United States	–	–	The recommended dose for phase 2 (RP2D) of onapristone ER	[156]
NCT04768426	Recruiting	N/A	Interventional	Single Group Assignment	United States	25	next-generation sequencing	Initial ctDNA detection levels, ctDNA levels, tumor genomic feature correlation, overall survival (OS), and relapse-free survival	[157]
NCT03318263	Completed	N/A	Interventional	Single Group Assignment	France	146	NGS	• Incidence of mutations in ESR1 • Incidence of PIK3CA and AKT1 mutations • Prevalence of mutations in AKT1, PIK3CA, and ESR1 in patients with and without endocrine resistance at enrollment • The frequency of AKT1, PIK3CA, and ESR1 mutations in patients depending on whether they underwent monotherapy or a combination of treatments • Prevalence of mutations from the initiation of treatment until the end of the follow-up period or progression in other noteworthy genes within the panel • Mutations in AKT1, PIK3CA, and ESR1 can be used to predict survival without progression	[158]
NCT05099978	Recruiting	–	Observational	Cohort	Japan and Malaysia	506	NGS	• Percentage of patients among all examination cases that had one or more genetic abnormalities • To report the concordance rate, the genomic anomalies of the tumor tissue and ctDNA will be merged	[159]
NCT03145961	Active, not recruiting	Randomized	Interventional	Parallel Assignment	United Kingdom	208	–	12 months after the positive ctDNA finding Positive ctDNA detection after a full year The lack of observable ctDNA or any sign of disease recurrence after six months (24 weeks) from the commencement of pembrolizumab treatment	[160]
NCT05428709	Terminated	N/A	Interventional	Single Group Assignment	United States	3	–	Changes in TGF-β, VEGF-A, S1P, TSP-1, and ctDNA levels	[161]
NCT04567420	RECRUITING	Randomized	Interventional	Parallel Assignment	United States	100	–	Clinically obvious metastatic or local BC is associated with positive ctDNA findings Examine if a positive ctDNA result indicates a clinical recurrence	[162]
NCT03947736	–	–	Observational	Cohort	China	200	ddPCR, and NGS	• Investigation of the correlation between the abundance of a particular mutation or plasma HER2 amplification and imaging evaluation in Individuals diagnosed with metastatic or recurrent BC • Examine the extent to which plasma HER2 ctDNA can predict therapy efficacy for recurrent or metastatic BC	[163]
NCT05814224	Recruiting	N/A	Interventional	Single Group Assignment	Italy	164	–	• Luminal BC therapy response is tracked by liquid biopsy • miRNA/ctDNA-based surveillance • Time to Progression (TTP), and PFS	[164]
NCT05625087	Recruiting	Randomized	Interventional	Parallel Assignment	France	162	–	• Survival without progression and the overall survival rate of the entire study group • To validate that individuals who were randomly assigned and had residual PIK3CA on their ctDNA had worse outcomes than patients who were not randomly assigned	[165]
NCT03017573	Recruiting	N/A	Interventional	Single Group Assignment	France	700	–	• Relationship between baseline clinic biological characteristics and the molecular/immunological profile of the tumor • Correlation between the immune system, de novo ctDNA mutations, and ctDNA levels	[166]
NCT03285412	Recruiting	Randomized	Interventional	Parallel Assignment	United States	120	–	ctDNA clearance	[167]
NCT05050890	–	–	Observational	Cohort	Brazil	38	–	• ctDNA concentration • Change from the beginning of the neoadjuvant treatment until the end of the ctDNA	[168]
NCT02546232	Active, not recruiting	Randomized	Interventional	Parallel Assignment	Norway	196	–	Cohorts I and II exhibit varying degrees of pathologic complete response (pCR), partial response (PR), complete response (CR), progressive disease (PD), and stable disease (SD) in treatment response Circulating tumor-DNA in plasma	[169]
NCT04256941	Completed	Randomized	Interventional	Parallel Assignment	United States	4	scatter plots	• ESR1 mutant allele fraction (MAF) and dynamics of circulating tumor deoxyribonucleic acid (ctDNA) • Prevalence of Estrogen Receptor 1 (ESR1) mutation emergence • Alterations in the tumor marker CA 15–3 cancer antigens • OS and PFS	[170]
NCT01957332	ACTIVE, NOT RECRUITING	N/A	Interventional	Single Group Assignment	Netherlands	217	–	Linkage between imaging, molecular analysis, and subsequent data with the analysis of DNA, miRNA, peptides, and RNA	[171]