Cell populations in human breast cancers are molecularly and biologically distinct with age
Year: 2025
Type: article
Abstract: Aging is associated with increased breast cancer risk, and the oldest and youngest patients have worse outcomes, irrespective of subtype. It is unknown how age affects cells in the breast tumor microenvironment or how they contribute to age-related pathology. Here we discover age-associated differences in cell states in human estrogen receptor-positive and triple-negative breast cancers using analyses of existing bulk and single-cell transcriptomic data. We generate and apply an Age-Specific Program ENrichment (ASPEN) analysis pipeline, revealing age-related changes, including increased tumor cell epithelial-mesenchymal transition and cancer-associated fibroblast inflammatory responses in triple-negative breast cancer. Estrogen receptor-positive breast cancer displays increased ESR1 expression and reduced vascular and immune cell metabolism with age. Cell interactome analysis reveals candidate signaling pathways that drive age-related cell states. Spatial analyses across independent clinical cohorts support the computational findings. This work identifies potential targets for age-adapted therapeutic interventions for breast cancer.
Source: Nature Aging
Institutions: Brigham and Women's Hospital, Harvard University, Dana-Farber Cancer Institute, Dana-Farber Brigham Cancer Center, Institut de Recerca Biomèdica Catalunya Sud, Hospital Universitari de Tortosa Verge de la Cinta, Universitat Rovira i Virgili, Garvan Institute of Medical Research, UNSW Sydney, Mass General Brigham, Dana-Farber/Harvard Cancer Center, Broad Institute, Harvard Stem Cell Institute, Massachusetts Institute of Technology
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funders: U.S. Department of Defense, U.S. Department of Health and Human Services, American Association for Cancer Research, American Cancer Society, Breast Cancer Research Foundation, Global Fund for Women, MPN Research Foundation, Edward P. Evans Foundation, Vera and Joseph Dresner Foundation, Pelotonia, National Breast Cancer Foundation, Petre Foundation, National Institutes of Health, Ludwig Center at Harvard, Medical Research Council, National Health and Medical Research Council, National Cancer Institute, U.S. National Library of Medicine, Congressionally Directed Medical Research Programs
Awards: G1323195535, G1393766945, G1555700463, Combined Targeting of Protein Translation Initiation and Apoptotic Machinery in Cancer, G4022669904, G4119534169, NEW DIAGNOSTIC AND THERAPEUTIC APPROACHES TO ERADICATING RECURRENT BREAST CANCER, G4938380697, G5609513807, G5850682332, Dissecting the cellular ecosystems and therapeutic vulnerabilities of breast cancer, Biomedical Informatics and Data Science Research Training Program (BIRT), G7433328520, G7494962475, G9000220833, Clonal analysis of cancer by mitochondrial DNA barcoding
OpenAlex ID: W4415849394