Minimal residual disease ctDNA testing in metastatic breast cancer patients with no radiological evidence of disease: Potentialclinical utility from real-worlddata.

e13075 Background: Liquid biopsy is increasingly recognized as a valuable tool for disease monitoring in metastatic breast cancer (MBC), with growing evidence supporting its role in treatment response assessment and minimal residual disease (MRD) detection across disease settings. This multi-institutional retrospective analysis evaluated the real-world use of circulating tumor DNA (ctDNA)–based MRD testing in patients(pts) with MBC who achieved radiological no evidence of disease (NED). Methods: We retrospectively analyzed pts with MBC treated at four institutions within the Precision Medicine Action for Cancer (PMAC) consortium who achieved radiological and/or metabolic complete response (CR) PET or CT imaging at any point during their MBC course. ctDNA-based MRD assessment was performed as part of routine clinical practice between September 2022 and December 2025 using plasma-only (Guardant Reveal, Guardant Health) or tissue-informed (Signatera) assays. Data were collected through retrospective review of electronic medical records under appropriate IRB approval. Analyses were descriptive. Results: 43 pts with MBC who achieved radiological NED and underwent MRD testing were identified, accounting for 225 ctDNA tests (median 5 tests per patient; IQR 1–8). Molecular subtypes included 36% luminal disease,24% triple-negative, and 40% HER2-positive disease. Median follow-up (fup) from primary breast cancer diagnosis was 63.2 months (IQR, 34.1–109.4). Longitudinal testing (≥2 ctDNA tests) was performed in 22 patients (51%). At first MRD assessment, 35 pts (81.4%) were MRD-negative: 27 had already achieved radiological CR, while in 8 patients MRD negativity preceded radiological NED by a median of 2.7 months (range 0.4-13.4). 5 pts had a positive MRD result at first evaluation concordant with radiological evidence of disease, and 3 had a positive first MRD test despite the absence of detectable disease. Among pts with at least one post-response MRD assessment, 26 pts (70.3%) showed persistently negative MRD results during longitudinal monitoring; among them, imaging was deferred in 7 cases and treatment de-escalation was pursued in 13 cases after at least one negative MRD test. Overall, 14 pts (32.6%) had at least one MRD-positive result during response fup; in six cases, longitudinal ctDNA monitoring anticipated radiological disease progression by a median of 1.05 months (range 0.5-3.7). At last fup, 20 pts remained radiologically disease-free with persistently negative ctDNA while in CR (median fup from first negative ctDNA test of 15.3 months). Conclusions: ctDNA MRD negativity was largely concordant with radiological or metabolic CR. This real-world cohort supports further prospective investigation to inform clinical management in patients with MBC achieving radiological NED.