GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE276nnn/GSE276755/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE276755GEOGSEfalseSystemic and breast chronic inflammation and hormone disposition promote a tumor-permissive environment for breast cancer in older women (Human Bulk RNA-Seq)Estrogen receptor positive (ER+) breast cancer, the most common subtype of breast cancer, is an age-related disease, with the peak incidence of diagnosis occurring around age 70 despite low circulating levels of estradiol. Despite the hormone sensitivity of these age-related tumors, our understanding of the interplay between the systemic and local hormonal disposition and chronic inflammaging is limited. We show that aged F344 rats treated with the DMBA/MPA carcinogen develop more tumors at faster rates than their younger counterparts, suggesting that the aged environment accelerates tumor growth. snRNA-seq of the tumors showed broad local immune dysfunction that was associated with circulating chronic inflammation. Across a broad cohort of specimens from patients with ER+ breast cancer and age-matched donors of normal breast tissue, we observe that even with E1-predominant estrogen disposition in the systemic circulation, tumors in older patients upregulate HSD17B7 expression to convert E1 to E2 in the TME. Age-related accumulation of tumor-associated macrophages serve as signaling hubs that integrate the E2 and chemokine-driven chronic inflammatory signaling in the TME, which polarize TAMs towards a CD206+/PD-L1+, immunosuppressive phenotype. Overall, these findings suggest that the host’s chronic inflammation and hormonal disposition shape the local tumor microenvironment and are critical contributors to the age-related nature of ER+ breast cancer development and growth.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 sapiens