{"doi":"10.1101/2025.05.20.25328012","title":"MammaTrace – a cell-free DNA methylation plasma only assay for minimal residual disease detection in breast cancer patients","abstract":"Introduction: Metastatic breast cancer (MBC) remains an incurable disease with a 5-year overall survival rate below 25%. Metastases often emerge from subclinical, disseminated tumor cells that persist despite systemic therapy of primary disease - referred to as minimal residual disease (MRD). Detecting MRD is critical for identifying patients at high risk of recurrence and enabling timely intervention. Methods: In this study, we developed MammaTrace, a plasma-only cell-free DNA (cfDNA) methylation-based MRD assay, informed by differentially methylated regions (DMRs) identified in MBC using whole genome bisulfite sequencing. MammaTrace was evaluated in an independent longitudinal cohort of early-stage breast cancer patients treated with curative intent. Results: MammaTrace achieved a sensitivity of 91% and specificity of 83%, with a median follow-up of 12.4 months. A positive MammaTrace score, indicative of MRD, preceded clinical or radiologic recurrence by a median of 457 days, providing a substantial lead time for therapeutic intervention to prevent progression to metastatic disease. Conclusions: MammaTrace enables detection of minimal residual disease in breast cancer patients, offering a substantial lead time before clinical recurrence. This approach may improve risk stratification and guide early therapeutic strategies to delay or prevent metastatic progression.","journal":"medRxiv","year":2025,"id":566554,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9677,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1266639,"name":"Alex J. Kalfa","orcid":"0009-0000-4930-3035","position":1,"is_corresponding":false},{"id":950955,"name":"Gerald Gooden","orcid":"0000-0002-3964-9996","position":2,"is_corresponding":false},{"id":378765,"name":"Juan Pablo Lewinger","orcid":"0000-0002-0692-2570","position":3,"is_corresponding":false},{"id":1470612,"name":"Marissa Pacheco","orcid":null,"position":4,"is_corresponding":false},{"id":1470613,"name":"Jessica Gayton","orcid":null,"position":5,"is_corresponding":false},{"id":817497,"name":"Darcy Spicer","orcid":null,"position":6,"is_corresponding":false},{"id":25448,"name":"John D. Carpten","orcid":"0000-0002-6862-2821","position":7,"is_corresponding":false},{"id":461451,"name":"Daphne Stewart","orcid":"0000-0001-9845-8375","position":8,"is_corresponding":false},{"id":256888,"name":"Heinz‐Josef Lenz","orcid":null,"position":9,"is_corresponding":false},{"id":7949,"name":"Chanita Hughes Halbert","orcid":"0000-0002-0103-6916","position":10,"is_corresponding":false},{"id":440363,"name":"Caryn Lerman","orcid":"0000-0002-7553-8724","position":11,"is_corresponding":false},{"id":260395,"name":"Joyce O’Shaughnessy","orcid":"0000-0001-6764-2807","position":12,"is_corresponding":false},{"id":597505,"name":"Barbara A. Pockaj","orcid":"0000-0001-8736-3020","position":13,"is_corresponding":false},{"id":702321,"name":"Bodour Salhia","orcid":"0000-0003-3843-3621","position":14,"is_corresponding":false},{"id":950954,"name":"David N. Buckley","orcid":"0000-0001-5161-7412","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-19T02:56:36.440192Z","pmid":"40475151","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}