{"doi":"10.1101/2024.05.28.596304","title":"Altered liver metabolism post-wean abolishes efficacy of vitamin D for breast cancer prevention in a mouse model","abstract":"Abstract Young women have increased risk of vitamin D deficiency, which may increase breast cancer incidence. Here, we assessed the anti-cancer efficacy of vitamin D in mouse models of young-onset breast cancer. In never-pregnant mice, vitamin D supplementation increased serum 25(OH)D and hepatic 1,25(OH) 2 D 3 , reduced tumor size, and associated with anti-tumor immunity. These anti-tumor effects were not replicated in a mouse model of postpartum breast cancer, where hepatic metabolism of vitamin D was suppressed post-wean, which resulted in deficient serum 25(OH)D and reduced hepatic 1,25(OH) 2 D 3 . Treatment with active 1,25(OH) 2 D 3 induced hypercalcemia exclusively in post-wean mice, highlighting metabolic imbalance post-wean. RNAseq revealed suppressed CYP450 expression postpartum. In sum, we provide evidence that vitamin D anti-tumor activity is mediated through immunomodulatory mechanisms and is ineffective in the post-wean window due to altered hepatic metabolism. These findings have implications for suppressed xenobiotic metabolism in postpartum women beyond vitamin D. Statement of Significance In a rodent model of postpartum breast cancer, weaning suppresses hepatic CYP450 activity and renders vitamin D supplementation ineffective, with implications for xenobiotic drug efficacy and safety. A tailored approach to therapy based on reproductive history is crucial for young breast cancer patients, and for healthcare strategies for postpartum women.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":491065,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9549,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":423740,"name":"Michelle Ozaki","orcid":"0000-0002-3356-9071","position":1,"is_corresponding":false},{"id":225125,"name":"Courtney B. Betts","orcid":"0000-0002-0432-0445","position":2,"is_corresponding":false},{"id":599563,"name":"Lisa A. Bleyle","orcid":null,"position":3,"is_corresponding":false},{"id":611183,"name":"Andrea E. DeBarber","orcid":"0000-0001-8910-0259","position":4,"is_corresponding":false},{"id":524776,"name":"Jaime Fornetti","orcid":null,"position":5,"is_corresponding":false},{"id":1062720,"name":"Abigail Liberty","orcid":"0000-0001-7494-1864","position":6,"is_corresponding":false},{"id":1336782,"name":"Elise de Wilde","orcid":null,"position":7,"is_corresponding":false},{"id":298314,"name":"Yi Zhang","orcid":"0000-0003-2498-3948","position":8,"is_corresponding":false},{"id":286283,"name":"Zheng Xia","orcid":"0000-0003-3364-8324","position":9,"is_corresponding":false},{"id":378493,"name":"Pepper Schedin","orcid":"0000-0003-4244-987X","position":10,"is_corresponding":false},{"id":1129186,"name":"Sarah M. Bernhardt","orcid":"0000-0002-9591-1231","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T02:08:41.211111Z","pmid":"38854129","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}