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Systemic and local chronic inflammation and hormone disposition promote a tumor-permissive environment for breast cancer in older women
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DOI：10.1038/s43587-026-01173-4.png)
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Abstract
En 中文
Estrogen receptor-positive (ER+) breast cancer is the most common subtype of breast cancer and is an age-related disease. How systemic and tumor microenvironment hormone signaling intersects with chronic inflammation and how this shapes aging-associated tumor biology remain incompletely understood. Here, using an aged rat model of ER+ tumors, we identify age-associated differences in tumor development and immune features. In parallel, analysis of samples from patients with ER+/HER2− breast cancer and age-matched controls demonstrated estrone-predominant systemic estrogen patterns and increased tumor HSD17B7 expression in older patients, consistent with enhanced local estrone-to-estradiol conversion. In patient-derived organoids from older women, pharmacologic inhibition of HSD17B7 reduced estrogen conversion and proliferation-associated transcriptional programs. Tumors from older patients also exhibited chemokine enrichment, including CCL2, associated with immunosuppressive macrophage features. Targeting both estrogen signaling and chemokine pathways attenuated macrophage polarization ex vivo. These findings support a model linking age-associated hormonal and inflammatory changes to features of a tumor-permissive microenvironment in ER+ breast cancer. Using an aged rat model, patient tissue samples and patient-derived organoids, Carleton et al. profiled age-associated differences in estrogen receptor-positive breast cancer, identifying inflammation and altered estrogen metabolism as possible contributors to age-related tumor permissiveness.
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