{"paper":{"title":"A senescent-immune reserve niche model for incomplete lobular involution in the aging breast","license":"http://arxiv.org/licenses/nonexclusive-distrib/1.0/","headline":"Persistent breast lobules after menopause are actively maintained by a senescent-immune reserve niche.","cross_cats":[],"primary_cat":"q-bio.TO","authors_text":"Amy C. Degnim, Darren J. Baker, Derek C. Radisky, Jaida C. Lue, Mark E. Sherman, Stacey J. Winham","submitted_at":"2026-05-12T21:39:11Z","abstract_excerpt":"Breast cancer incidence rises with age and peaks across the menopausal transition, yet why some postmenopausal lobules persist, and why that persistence predicts cancer risk, remains unresolved. Incomplete age-related lobular involution is one of the strongest tissue-level predictors of subsequent breast cancer, but it is still commonly viewed as passive failure of hormonally driven regression. This Review proposes a different framework: persistent lobules are maintained by an active reserve niche that outlasts its reproductive function. By integrating breast epidemiology, mammary stromal biol"},"claims":{"count":4,"items":[{"kind":"strongest_claim","text":"Persistent lobules are maintained by an active reserve niche that outlasts its reproductive function, created when impaired immune surveillance allows inflammatory paracrine signaling, macrophage reprogramming, and immune evasion to form a self-sustaining senescent-immune niche lock.","source":"verdict.strongest_claim","status":"machine_extracted","claim_id":"C1","attestation":"unclaimed"},{"kind":"weakest_assumption","text":"That the integration of existing epidemiology, stromal biology, senescence, and immune surveillance literature is sufficient to establish menopause as a control point where tissue fate diverges specifically via senescent-immune interactions, rather than other unmodeled factors.","source":"verdict.weakest_assumption","status":"machine_extracted","claim_id":"C2","attestation":"unclaimed"},{"kind":"one_line_summary","text":"Persistent breast lobules after menopause are maintained by an active senescent-immune niche that impairs clearance and sustains inflammation, explaining their link to elevated cancer risk.","source":"verdict.one_line_summary","status":"machine_extracted","claim_id":"C3","attestation":"unclaimed"},{"kind":"headline","text":"Persistent breast lobules after menopause are actively maintained by a senescent-immune reserve niche.","source":"verdict.pith_extraction.headline","status":"machine_extracted","claim_id":"C4","attestation":"unclaimed"}],"snapshot_sha256":"d03bb4a96ff1d932ee8f0478749167e7422f862914100416d677839ddacf95e4"},"source":{"id":"2605.13902","kind":"arxiv","version":1},"verdict":{"id":"9e4f7f50-733d-46c2-8f5c-429f44758d1b","model_set":{"reader":"grok-4.3"},"created_at":"2026-05-15T05:47:34.924446Z","strongest_claim":"Persistent lobules are maintained by an active reserve niche that outlasts its reproductive function, created when impaired immune surveillance allows inflammatory paracrine signaling, macrophage reprogramming, and immune evasion to form a self-sustaining senescent-immune niche lock.","one_line_summary":"Persistent breast lobules after menopause are maintained by an active senescent-immune niche that impairs clearance and sustains inflammation, explaining their link to elevated cancer risk.","pipeline_version":"pith-pipeline@v0.9.0","weakest_assumption":"That the integration of existing epidemiology, stromal biology, senescence, and immune surveillance literature is sufficient to establish menopause as a control point where tissue fate diverges specifically via senescent-immune interactions, rather than other unmodeled factors.","pith_extraction_headline":"Persistent breast lobules after menopause are actively maintained by a senescent-immune reserve niche."},"references":{"count":10,"sample":[{"doi":"","year":2020,"title":"Increased systemic inflammation and altered distribution of T -cell subsets in postmenopausal women","work_id":"7ed4b5c2-bf5b-4249-b1a7-9490f286aeb7","ref_index":1,"cited_arxiv_id":"","is_internal_anchor":false},{"doi":"","year":1999,"title":"Suppression of epithelial apoptosis and delayed mammary gland involution in mice with a conditional knockout of Stat3","work_id":"aed17ca5-c94d-419e-b4d5-090951c5f285","ref_index":2,"cited_arxiv_id":"","is_internal_anchor":false},{"doi":"","year":2002,"title":"Lancet 360(9328): 187-195. Cousins, F. L., C. E. Filby and C. E. Gargett (2021)","work_id":"f6e61532-65c9-4a23-9070-f40a824d65b2","ref_index":3,"cited_arxiv_id":"","is_internal_anchor":false},{"doi":"","year":2023,"title":"Regulation of adult stem cell quiescence and its functions in the maintenance of tissue integrity","work_id":"088bd8c8-75cf-405a-b59b-35c03baa3f22","ref_index":4,"cited_arxiv_id":"","is_internal_anchor":false},{"doi":"","year":2017,"title":"Association between local inflammation and breast tissue age- related lobular involution among premenopausal and postmenopausal breast cancer patients","work_id":"d75a11f3-767c-47c8-9396-745c8703f7f3","ref_index":5,"cited_arxiv_id":"","is_internal_anchor":false}],"resolved_work":10,"snapshot_sha256":"d1eeb173a6a8241c32336f9030a8f76eee175c3bdba4851133ca0ff78f138660","internal_anchors":0},"formal_canon":{"evidence_count":1,"snapshot_sha256":"2f723b92f2bc6f33e3a08aad45a60f539477d4cc3c0488109771483c22e30b79"},"author_claims":{"count":0,"strong_count":0,"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"builder_version":"pith-number-builder-2026-05-17-v1"}