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Onc."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    This study applies joint modeling (JM) of longitudinal and time-to-event data to circulating tumor DNA (ctDNA) dynamics measured by liquid biopsy in metastatic breast cancer (mBC), with a focus on dynamic prediction. Unlike traditional prognostic approaches that rely on static biomarkers, JM captures the continuous evolution of a methylation-based tumor fraction (TF) and links these changes to clinical outcomes. Serial liquid biopsies from 49 patients with hormone receptor\u2013positive\/HER2-negative mBC treated with endocrine therapy plus a CDK4\/6 inhibitor were analyzed using the Guardant Reveal assay. JM combined a flexible longitudinal sub-model to characterize temporal TF trajectories with a Cox proportional hazards model for overall survival (OS) and time to treatment discontinuation (TTD). The most recent TF estimate was strongly associated with both OS and TTD (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001), demonstrating an inverse relationship between TF and prognosis. These findings highlight the value of JM for generating patient-specific, dynamically updated predictions that may support real-time, personalized clinical decision-making in mBC management.\n                  <\/jats:p>","DOI":"10.1038\/s41698-026-01498-8","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T22:05:32Z","timestamp":1780524332000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Longitudinal evaluation of serial ctDNA kinetics using joint modeling in patients with metastatic breast cancer"],"prefix":"10.1038","volume":"10","author":[{"given":"Christopher","family":"Pretz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesu\u0301s","family":"Fuentes-Antra\u0301s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasha","family":"Main","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Dou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Van de Laar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline M.","family":"Weipert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amar","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eitan","family":"Amir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle B.","family":"Nadler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celeste","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hal K.","family":"Berman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lillian L.","family":"Siu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe L.","family":"Bedard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell J.","family":"Elliott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Cescon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"1498_CR1","doi-asserted-by":"publisher","DOI":"10.1186\/s12874-020-00976-2","volume":"20","author":"M Alsefri","year":"2020","unstructured":"Alsefri, M., Sudell, M., Garc\u00eda-Fi\u00f1ana, M. & Kolamunnage-Dona, R. 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Weipert: Employee of Guardant Health; Bryan Lin: Employee of Guardant Health; Amar Das: Employee of Guardant Health; Eitan Amir: Honoraria (self): Sandoz, Seagen, Consulting (self): AstraZeneca, Novartis; Michelle B. Nadler: Speaker honorarium and consulting fees from Novartis and Exact Sciences, outside of the scope of this submitted work; Celeste Yu: None; Hal K. Berman: None; Lillian L. Siu: Scientific advisory board (self): Merck, Pfizer, AstraZeneca, Roche, GlaxoSmithKline, Voronoi, Arvinas, Navire, Relay, Daiichi Sankyo, Amgen, Marengo, Medicenna, Tubulis, LTZ Therapeutics, Pangea, Break Through Cancer, Clinical trial support (institution): Novartis, Bristol-Myers Squibb, Pfizer, Boehringer-Ingelheim, GlaxoSmithKline, Roche\/Genentech, AstraZeneca, Merck, Celgene, Astellas, Bayer, Abbvie, Amgen, Symphogen, Mirati, BioNTech, 23Me, EMD Serono, Stock ownership (spouse): Agios, Leadership roles (spouse): Treadwell Therapeutics; Philippe L. Bedard: Research Funding (to Institution): Amgen, AstraZeneca, Bayer, Bicara, BristolMyersSquibb, Genentech\/Roche, Gilead, GlaxoSmithKline, Lilly\/Loxo, Medicenna, Merck, Nektar, Novartis, PTC Therapeutics, Sanofi, SeaGen, Servier, SignalChem Life Sciences, Takeda, Zymeworks, Honoraria\/Consultancy (uncompensated): Zymeworks, Lilly, Seattle Genetics, Merck, Amgen, Gilead, Jannsen, Repare; Mitchell J. Elliott: Honoraria\/Consultancy: Gilead; David W. Cescon: consultancy and advisory: AstraZeneca, Daiichi Sankyo, Exact Sciences, GenomeRx, Gilead, GlaxoSmithKline, Inivata\/NeoGenomics, Knight Therapeutics, Lilly, Merck, Novartis, Pfizer, Roche and SAGA; research support to institution: AstraZeneca, GenomeRx, Guardant Health, Grail, Gilead, GlaxoSmithKline, Inivata\/NeoGenomics, Knight, Merck, PearBio, Pfizer, ProteinQure, RayzeBio and Roche.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"362"}}