Exploring therapeutic effects of a CDK4/6 inhibitor on suppressing late recurrence in breast cancer

Exploring therapeutic effects of a CDK4/6 inhibitor on suppressing late recurrence in breast cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Exploring therapeutic effects of a CDK4/6 inhibitor on suppressing late recurrence in breast cancer Akira Nakamura, Yukinori Ozaki, Satoshi Morita This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8783973/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 11 You are reading this latest preprint version Abstract Abemaciclib, a cyclin-dependent kinase 4/6 inhibitor, was previously examined in a randomized clinical trial for the adjuvant setting, using invasive disease-free survival (IDFS) as the primary endpoint. Analysis of these IDFS data using a piecewise hazard model demonstrated that the hazard ratio for IDFS remained reduced even after completion of the two-year abemaciclib treatment, possibly yielding a sustained recurrence-suppressive effect beyond the treatment period. Preclinical and clinical observations have implicated cancer stem cells (CSCs) in treatment-resistant recurrence, including late recurrence, in breast cancer. CSCs are believed to enter a dormant state, enabling them to evade therapeutic targeting and later give rise to recurrence. Therefore, recurrence events cannot be suppressed following treatment conclusion without therapeutic efficacy against dormant CSCs, even if recurrence-suppressive effects are observed during the treatment period. In the current study, we aimed to explore the possible mechanisms underlying the long-term suppressive effect of abemaciclib treatment on recurrence using an existing tumor recurrence prediction model with suitable modifications. This model was operated using CSC-related assumptions, specifically that two distinct sources of recurrence were present after primary tumor resection: i) metastatic cells already in a proliferative state at the time of surgery and ii) proliferative metastatic cells newly derived from CSCs after surgery. The results of prediction-based investigations, including the current study, have suggested that therapeutic effects targeting CSCs could at least partially account for the sustained suppression of recurrence observed with abemaciclib treatment of breast cancer. Biological sciences/Cancer Health sciences/Oncology CDK4/6 inhibitor breast cancer late recurrence cancer stem cells recurrence prediction Full Text Additional Declarations Competing interest reported. The authors declare the following competing interests: Y.O. reported personal fees from Eli Lilly, Pfizer, Kyowa Kirin, and Daiichi Sankyo outside the submitted work. S.M. reported personal fees from AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Taiho Pharmaceutical, Eli Lily, Merck Sharp & Dohme, Nippon Boehringer Ingelheim, Ono Pharmaceutical, Pfizer, Eisai, Novartis, and Kyowa Kirin outside the submitted work. A.N. declares no competing interests. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 16 Apr, 2026 Reviews received at journal 15 Apr, 2026 Reviewers agreed at journal 23 Mar, 2026 Reviewers agreed at journal 23 Mar, 2026 Reviews received at journal 25 Feb, 2026 Reviewers agreed at journal 17 Feb, 2026 Reviewers invited by journal 17 Feb, 2026 Editor invited by journal 09 Feb, 2026 Editor assigned by journal 04 Feb, 2026 Submission checks completed at journal 04 Feb, 2026 First submitted to journal 04 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8783973","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":593267788,"identity":"8221ccb6-b0e1-4326-a94f-f7d9d5acbeab","order_by":0,"name":"Akira Nakamura","email":"","orcid":"","institution":"Kyoto University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Akira","middleName":"","lastName":"Nakamura","suffix":""},{"id":593267790,"identity":"1e46f672-82a0-4f45-a567-c18382b1240c","order_by":1,"name":"Yukinori Ozaki","email":"","orcid":"","institution":"The Cancer Institute Hospital of Japanese Foundation for Cancer Research","correspondingAuthor":false,"prefix":"","firstName":"Yukinori","middleName":"","lastName":"Ozaki","suffix":""},{"id":593267791,"identity":"c5770499-be5a-433c-8819-23f0b7e50a61","order_by":2,"name":"Satoshi Morita","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDElEQVRIie3RQUrEMBSA4RcKnU0O8GAgvUJLYRSUepWUwHTT6gEULQi6GVxKhopnCQQ6mx6gMJtx76KrYVZirKIFG8elYP5VKHy8lxTA5fqrcQCGQM1JDb6S8ifCIf4k9FfEjEnlN2IruNd197RLsqUs6g00mp1MSh/hIgGvGh8TrudCci6KCk+zEFodU6oMqQWQBzVOpnls7uIVj5jPEDqdLvBsi+ArIJKPL1b15CpjX4SbKS92AuueaD7tSftByI2dvN0F+HwVLRfPByFvspg2yjtM7wS13SWohCa74/MAV/ls09VHbHJbkrbbJiyyvNgw3/yf6/ejWYlGcq8wBOBysADuJy6Xy/UvegUNzVid6TdvDgAAAABJRU5ErkJggg==","orcid":"","institution":"Kyoto University Graduate School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Satoshi","middleName":"","lastName":"Morita","suffix":""}],"badges":[],"createdAt":"2026-02-04 08:53:55","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8783973/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8783973/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103058563,"identity":"88611fcb-fafc-4a7e-b22c-1bd6d31d3cd7","added_by":"auto","created_at":"2026-02-20 09:35:27","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1268042,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.ScientificReports.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8783973/v1_covered_8b87f15d-1020-4b67-b80a-30d539108c29.pdf"}],"financialInterests":"Competing interest reported. 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