Mol Oncol. 2025 Nov 27. doi: 10.1002/1878-0261.70170. Online ahead of print.

ABSTRACT

Breast cancer is known for late recurrences, yet current follow-up lacks radiological or blood-based monitoring for systemic relapse. This study evaluated circulating tumor DNA (ctDNA) monitoring for early detection of systemic relapse after curative treatment. In this case-control study of 70 patients with operable breast cancer (35 with relapse and 35 without relapse), blood samples were collected every 6-12 months during a median 8.3-year follow-up. ctDNA was analyzed by targeted DNA sequencing using Oncomine™ Breast cfDNA Research Assay v2, and results were compared to genetic analysis of tumor and metastasis biopsies. ctDNA was detected at relapse in 19 of 35 (54%) patients with disease relapse and preceded clinical or radiological relapse detection in 17, with a median lead time of 10.3 months. In 13 (68%) patients, there was concordance with tumor mutations, and in seven patients, there was also concordance with metastasis. Among the relapse-free patients, seven were ctDNA-positive postsurgery, and only one of them had a match among the tumor variants. These findings suggest serial ctDNA analysis may enable earlier detection of systemic relapse in patients with operable breast cancer.

PMID:41307327 | DOI:10.1002/1878-0261.70170

Cancers (Basel). 2025 Nov 18;17(22):3692. doi: 10.3390/cancers17223692.

ABSTRACT

The role of circulating tumor DNA (ctDNA) in gastroesophageal adenocarcinoma (GEA) has expanded in recent years. In resectable disease, postoperative ctDNA is able to detect patients at highest risk of recurrence months before scans. Tumor-informed assays provide the best sensitivity and emerging methylation assays are useful when tissue is scarce. In metastatic GEA, baseline ctDNA burden correlates with prognosis, and a decrease in ctDNA level after treatment initiation reflects therapeutic response. It can also uncover actionable targets, including ERBB2, FGFR2, and MSI-H, and detect resistance that can arise after starting treatment. Limitations include variable assay performance, low shedding in some tumors, clonal hematopoiesis confounding, and a lack of randomized data showing that ctDNA-guided changes improve outcomes. Ongoing trials are testing MRD-guided escalation/de-escalation and ctDNA-directed biomarker therapy. In this review, we evaluate the role of ctDNA in GEA cancers over recent years.

PMID:41301057 | PMC:PMC12650754 | DOI:10.3390/cancers17223692