Table 1.

Ongoing clinical studies testing ctDNA-based surveillance and treatment strategies in early-stage breast cancer

Trial number	No. of patients	Setting	Timing of ctDNA test	Primary endpoint	Study intervention/objective
NCT05058183	400	Adjuvant—Stage I HER2+ and TNBC	Before and after surgery	Incidence of pts with positive ctDNA after surgery	Chemotherapy de-escalation in case of negative ctDNA
NCT04768426	25	Adjuvant—TNBC receiving adjuvant capecitabine	Baseline and 6 months	Detection of ctDNA at baseline and 6 months	Identification of patients not benefiting from capecitabine
NCT04530890	1000a	Adjuvant and neoadjuvant	Start of treatment, during treatment, at progression	Prognostic impact of ctDNA on mortality	Evaluation of the prognostic role of ctDNA on risk of death
NCT04567420	100	Adjuvant—Stage II–III HR+/HER2− BC at high risk of relapse	Every 4/6 months concomitant to follow-up visits	ctDNA positivity and RFS	Patients receiving adjuvant endocrine treatment with ctDNA positivity will be randomized to fulvestrant and palbociclib or to continue standard of care treatment
NCT03357120	180	Surveillance after neoadjuvant chemotherapy	After surgery and every 6 months thereafter for 5 years	Prognostic impact on RFI at 3 years	NA
NCT04985266 (TRAK-ER)	1100	Adjuvant—HR+/HER2− at high risk of relapse	Every 3 months for up to 3 years	Incidence of ctDNA detection during surveillance and RFS	Patients with ctDNA detection under endocrine therapy and without evidence of metastasis will be randomized to fulvestrant and palbociclib or standard endocrine therapy
NCT04501523 (Apollo)	460	Adjuvant—TNBC with and without RD	Baseline, after NACT, and after surgery	5-year DFS	Patients with ctDNA detection will be randomized to adjuvant therapy with capecitabine ± tislelizumab
NCT04849364 (PERSEVERE)	197	Adjuvant—TNBC with RD	After surgery	2-year DFS	Patients with residual disease after neoadjuvant chemotherapy and with ctDNA detection will be randomized to different treatments on the basis of identification of genomic targets
NCT05512364 (EORTC – Treat ctDNA)	220	Adjuvant—Stage IIB and III HR+/HER2−	Baseline and every 6 months for up to 3 years	DMFS	Patients with ctDNA detection under endocrine therapy and without evidence of metastasis will be randomized to elacestrant or standard endocrine therapy
NCT03709134	100	Neoadjuvant	NA	pCR	Determination of the prognostic and predictive role of genomic markers
NCT04803539 (Artemis)	260	Adjuvant—TNBC	After surgery and/or adjuvant chemotherapy	iDFS	Patients with positive ctDNA will be randomized to capecitabine ± camrelizumab + apatinib
NCT05433753 (Harmony)	60	Surveillance—Stage IIA–IIIC HER2+	NA	iDFS	Identify a relation between ctDNA detection and recurrence
NCT03285412 (Leader)	120	Adjuvant—HR+/HER2−	Baseline	ctDNA clearance	Patients with ctDNA detection will receive ribociclib in addition to standard adjuvant endocrine therapy
NCT04915755 (ZEST)	800	Adjuvant—TNBC and HER2− BC with BRCA 1/2 mutations	Longitudinal monitoring of ctDNA after surgery or adjuvant treatment	DFS	Patients with ctDNA detection will be randomized to treatment with niraparib for 3 years or placebo
NCT05388149	15	Adjuvant—Stage I–III HER2+	After 2–6 cycles of T-DM1	ctDNA clearance	Patients with ctDNA detection will receive adjuvant neratinib and T-DM1
NCT04434040 (ASPRIA)	40	Adjuvant—TNBC with residual disease	After completion of all local and neoadjuvant therapies	ctDNA clearance after 18 weeks	Patients with ctDNA detection will receive adjuvant atezolizumab and sacituzumab govitecan

ctDNA circulating tumor DNA, TNBC triple-negative breast cancer, pCR pathological complete response, RFS relapse-free survival, RFI relapse-free interval, RD residual disease, NACT neoadjuvant chemotherapy, DFS disease-free survival, DMFS distant metastasis-free survival, iDFS invasive disease-free survival

^aIncluding patients with digestive and gynecological malignancies as well