Personalized whole-genome-based ctDNA dynamics during neoadjuvant therapy across breast cancer subtypes: results from MONITOR-Breast.
Publication Title
Future Oncol
Document Type
Article
Publication Date
7-1-2026
Keywords
Humans; Breast Neoplasms; Female; Circulating Tumor DNA; Neoadjuvant Therapy; Neoplasm, Residual; Pathologic Complete Response; Middle Aged; Biomarkers, Tumor; Prospective Studies; Adult; Whole Genome Sequencing; Aged; Precision Medicine; Neoplasm Staging; breast cancer; ctDNA; molecular residual disease; neoadjuvant therapy; response monitoring.; california; burbank; psjmc; genomics
Abstract
PURPOSE: Pathological complete response (pCR) after neoadjuvant therapy (NAT) strongly associates with reduced breast cancer relapse risk. Circulating tumor DNA (ctDNA) shows promise as a therapy-response biomarker, but prior studies had limited sampling and assay sensitivity. MONITOR-Breast characterized ctDNA dynamics across NAT at high temporal resolution using an ultrasensitive molecular residual disease (MRD) assay.
EXPERIMENTAL DESIGN: In this prospective observational study, 154 enrolled patients with breast cancer (all subtypes, Stages I-III) were tested at baseline, throughout NAT, and post-surgery using a whole genome sequencing-based MRD assay tracking up to 1,000 variants per patient.
RESULTS: Baseline ctDNA was detected in 93% of patients, with 20% detected in the ultrasensitive range (< 100 parts per million). Post-NAT ctDNA positivity strongly associated with residual disease (RD) (odds ratio (OR)>20,
CONCLUSIONS: Frequent, ultrasensitive ctDNA assessment provided comprehensive characterization of treatment response, revealing opportunities for de-escalation in early responders and escalation in those with persistent ctDNA.
Area of Special Interest
Women & Children
Area of Special Interest
Cancer
Specialty/Research Institute
Oncology
DOI
10.1080/14796694.2026.2690165