ArticleEBioMedicine2026
Menopausal timing and senescent-immune coupling in age-related lobular involution of the human breast: a longitudinal cohort study.
Article in EBioMedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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14 authors.
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Abstract
backgroundIncomplete postmenopausal breast involution leaves persistent epithelial-rich lobules and elevated breast density in about 40% of women and is associated with higher breast cancer risk, but why remodelling stalls remains unclear.
methodsWe studied a longitudinal cohort of 81 women with paired benign breast biopsies (baseline age 45-55 years; follow-up 2-10 years), all with baseline NanoString transcriptomics and two-timepoint digital morphometry, and with multiplex immunofluorescence in spatial-imaging subsets (baseline n = 14-16 depending on panel; follow-up n = 14). A separate postmenopausal endpoint cohort (12 women: eight noninvoluted, four completely involuted), profiled by genome-wide expression array and multiplex immunofluorescence, defined the persistent-lobule phenotype.
findingsNoninvoluted postmenopausal tissue retained a proliferation-competent, tumour-associated epithelial state and showed immune accumulation at lobular boundaries with reduced access to p16
interpretationMenopausal timing conditions whether senescent-immune programmes couple to productive clearance or to spatially uncoupled surveillance and persistent risk-associated tissue. Biomarker interpretation should therefore be anchored to menopausal timing.
fundingCasey DeSantis Cancer Fund and US National Cancer Institute.
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