Cell Populations in Human Breast Cancers are Molecularly and Biologically Distinct with Age

Cell Populations in Human Breast Cancers are Molecularly and Biologically Distinct with Age | 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 Analysis Cell Populations in Human Breast Cancers are Molecularly and Biologically Distinct with Age Sandra McAllister, Adrienne Parsons, Esther Sauras Colon, Milos Spasic, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5167339/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 Aging is associated with increased breast cancer risk and outcomes are worse for the oldest and youngest patients, regardless of subtype. It is not known how cells in the breast tumor microenvironment are impacted by age and how they might contribute to age-related disease pathology. Here, we discover age-associated differences in cell states and interactions in human estrogen receptor-positive (ER+) and triple-negative breast cancers (TNBC) using new computational analyses of existing single-cell gene expression data. Age-specific program enrichment (ASPEN) analysis reveals age-related changes, including increased tumor cell epithelial-mesenchymal transition, cancer-associated fibroblast inflammatory responses, and T cell stress responses and apoptosis in TNBC. ER+ breast cancer is dominated by increased cancer cell estrogen receptor 1 (ESR1) and luminal cell activity, reduced immune cell metabolism, and decreased vascular and extracellular matrix (ECM) remodeling with age. Cell interactome analysis reveals candidate signaling pathways that drive many of these cell states. This work lays a foundation for discovery of age-adapted therapeutic interventions for breast cancer. Biological sciences/Cancer/Breast cancer Biological sciences/Computational biology and bioinformatics Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Table1.xlsx Table2.xlsx Table3.xlsx Table4.xlsx Table5.xlsx Table6.xlsx Table7.xlsx SupplementaryInformation.pdf 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-5167339","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Analysis","associatedPublications":[],"authors":[{"id":365951898,"identity":"0f4c77a6-efee-41bf-99ad-9d5520a0495b","order_by":0,"name":"Sandra 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