CDK4/6 Inhibitor Rechallenge Therapy in Advanced Breast Cancer

CDK4/6 Inhibitor Rechallenge Therapy in Advanced 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 Research Article CDK4/6 Inhibitor Rechallenge Therapy in Advanced Breast Cancer Yuhan Sun, Yang Zhao, Xinyang Yu, Yuanfu Qi, Xin Dai This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7130495/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Hormone receptor (HR)-positive is the most common subtype in female breast cancer (BC) patients, and endocrine therapy (ET) is the primary treatment for HR-positive BC. Clinical studies have confirmed that cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with ET can significantly prolong the progression-free survival (PFS) of advanced BC patients. Consequently, the combination of CDK4/6 inhibitors and ET has been established as a first-line treatment for advanced HR-positive BC or a standard treatment following ET progression. However, the regimen after CDK4/6 inhibitor treatment failure remains highly controversial, and the reported clinical outcomes of CDK4/6 inhibitor rechallenge are inconsistent. Preclinical studies have collected evidence suggesting that multiple mechanisms may contribute to intrinsic or acquired resistance to CDK4/6 inhibitors. Future research should further investigate the translational relationship between resistance mechanisms and clinical efficacy, and identify biomarkers to screen the benefit population from CDK4/6 inhibitor rechallenge therapy, developping individualized treatment strategies. breast cancer hormone receptor positive endocrine therapy CDK4/6 inhibitor rechallenge Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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-7130495","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":488736939,"identity":"a0aec8b3-3bca-4a7c-96d3-8b86d2810798","order_by":0,"name":"Yuhan Sun","email":"","orcid":"","institution":"Shandong University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yuhan","middleName":"","lastName":"Sun","suffix":""},{"id":488736940,"identity":"d8e3bf29-0b69-48ef-bb95-ab052b250c66","order_by":1,"name":"Yang Zhao","email":"","orcid":"","institution":"Shandong University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yang","middleName":"","lastName":"Zhao","suffix":""},{"id":488736941,"identity":"be1aa092-2bc1-41ce-82f4-a6dacd6f2238","order_by":2,"name":"Xinyang Yu","email":"","orcid":"","institution":"Shandong University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Xinyang","middleName":"","lastName":"Yu","suffix":""},{"id":488736942,"identity":"24b3a384-540d-434c-afdb-00623f5f7f75","order_by":3,"name":"Yuanfu Qi","email":"","orcid":"","institution":"Shandong University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yuanfu","middleName":"","lastName":"Qi","suffix":""},{"id":488736943,"identity":"1dfb914e-2df6-454e-bbb7-06cb90b9c7b5","order_by":4,"name":"Xin Dai","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2ElEQVRIiWNgGAWjYDCCA4wNDAkMEnJs7M0HDnyoIF6LhTE/z7HEgzPOEKUFTFYkzpyRY3yYt4UIHXzHD7dJPNwhwbjhzJkPB3gbGOT5xQ7g1yJ5JrHZIPGMBLPB8d4NByR3MBjOnJ2AX4vBgcTGB4ltEmwGZ85uOGB4hiHB4DYhLecfNhwAauExuJHzAMggRssNiC0SkjNyGA4cJEaL5I2HQL+0SRgAA9ngYMMZCcJ+4Tuf/kzyZ1tdfRt78+PPfyps5PmlCWhBBxKkKR8Fo2AUjIJRgB0AAOt6UPrMNCsqAAAAAElFTkSuQmCC","orcid":"","institution":"Shandong University of Traditional Chinese Medicine","correspondingAuthor":true,"prefix":"","firstName":"Xin","middleName":"","lastName":"Dai","suffix":""}],"badges":[],"createdAt":"2025-07-15 12:23:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7130495/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7130495/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":87511898,"identity":"d393e73c-45d6-4f94-813b-8b1d2ff549eb","added_by":"auto","created_at":"2025-07-24 15:47:02","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":249217,"visible":true,"origin":"","legend":"","description":"","filename":"CDK46InhibitorRechallengeTherapyinAdvancedBreastCancer.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7130495/v1_covered_fc328b47-01ae-4d13-811b-4cd214f558b4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"CDK4/6 Inhibitor Rechallenge Therapy in Advanced Breast Cancer","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"breast cancer, hormone receptor positive, endocrine therapy, CDK4/6 inhibitor, rechallenge","lastPublishedDoi":"10.21203/rs.3.rs-7130495/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7130495/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Hormone receptor (HR)-positive is the most common subtype in female breast cancer (BC) patients, and endocrine therapy (ET) is the primary treatment for HR-positive BC. Clinical studies have confirmed that cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with ET can significantly prolong the progression-free survival (PFS) of advanced BC patients. Consequently, the combination of CDK4/6 inhibitors and ET has been established as a first-line treatment for advanced HR-positive BC or a standard treatment following ET progression. However, the regimen after CDK4/6 inhibitor treatment failure remains highly controversial, and the reported clinical outcomes of CDK4/6 inhibitor rechallenge are inconsistent. Preclinical studies have collected evidence suggesting that multiple mechanisms may contribute to intrinsic or acquired resistance to CDK4/6 inhibitors. 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