biostudies-literatureUnknownBernhardt SMNCI NIH HHSYoung 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)₂D₃, 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)₂D₃. Treatment with active 1,25(OH)₂D₃ induced hypercalcemia exclusively in post-wean mice, highlighting metabolic imbalance post-wean. RNAseq revbioRxiv : the preprint server for biology2024.05.28.596304https://www.ebi.ac.uk/biostudies/studies/S-EPMC11160686biostudies-literatureAltered liver metabolism post-wean abolishes efficacy of vitamin D for breast cancer prevention in a mouse model.PMC11160686P30 CA069533R01 CA169175DeBarber AEXia ZSchedin POzaki MKFornetti JZhang YBernhardt SMWilde De EBleyle LABetts CLiberty ALfalseAltered liver metabolism post-wean abolishes efficacy of vitamin D for breast cancer prevention in a mouse model.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)₂D₃, 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)₂D₃. Treatment with active 1,25(OH)₂D₃ induced hypercalcemia exclusively in post-wean mice, highlighting metabolic imbalance post-wean. RNAseq rev2024-01-01T00:00:00Z2024 Jun2026-07-05T03:17:04.223Z2026-07-05T03:12:23.597ZS-EPMC111606863885412910.1101/2024.05.28.596304