{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T21:18:41Z","timestamp":1768511921750,"version":"3.49.0"},"posted":{"date-parts":[[2024,6,2]]},"group-title":"Cancer Biology","reference-count":70,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,6,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  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)\n                  <jats:sub>2<\/jats:sub>\n                  D\n                  <jats:sub>3<\/jats:sub>\n                  , 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)\n                  <jats:sub>2<\/jats:sub>\n                  D\n                  <jats:sub>3<\/jats:sub>\n                  . Treatment with active 1,25(OH)\n                  <jats:sub>2<\/jats:sub>\n                  D\n                  <jats:sub>3<\/jats:sub>\n                  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.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Statement of Significance<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.05.28.596304","type":"posted-content","created":{"date-parts":[[2024,6,2]],"date-time":"2024-06-02T19:55:30Z","timestamp":1717358130000},"source":"Crossref","is-referenced-by-count":0,"title":["Altered liver metabolism post-wean abolishes efficacy of vitamin D for breast cancer prevention in a mouse model"],"prefix":"10.64898","author":[{"given":"Sarah M","family":"Bernhardt","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle K","family":"Ozaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Courtney","family":"Betts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa A","family":"Bleyle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea E","family":"DeBarber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaime","family":"Fornetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abigail L","family":"Liberty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elise","family":"De Wilde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng","family":"Xia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pepper","family":"Schedin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"issue":"1","key":"2024060605400568000_2024.05.28.596304v1.1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.7326\/M18-1323","article-title":"Breast Cancer Risk After Recent Childbirth: A Pooled Analysis of 15 Prospective Studies","volume":"170","year":"2019","journal-title":"Ann Intern Med"},{"key":"2024060605400568000_2024.05.28.596304v1.2","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-020-07248-8"},{"issue":"1","key":"2024060605400568000_2024.05.28.596304v1.3","doi-asserted-by":"crossref","first-page":"e186997","DOI":"10.1001\/jamanetworkopen.2018.6997","article-title":"Association Between Postpartum Breast Cancer Diagnosis and Metastasis and the Clinical Features Underlying Risk","volume":"2","year":"2019","journal-title":"JAMA Netw Open"},{"issue":"6","key":"2024060605400568000_2024.05.28.596304v1.4","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/S1470-2045(21)00183-2","article-title":"The definition of pregnancy-associated breast cancer is outdated and should no longer be used","volume":"22","year":"2021","journal-title":"Lancet Oncol"},{"key":"2024060605400568000_2024.05.28.596304v1.5","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-016-3989-3"},{"issue":"10","key":"2024060605400568000_2024.05.28.596304v1.6","doi-asserted-by":"crossref","first-page":"e2236763","DOI":"10.1001\/jamanetworkopen.2022.36763","article-title":"Young-Onset Breast Cancer Outcomes by Time Since Recent Childbirth in Utah","volume":"5","year":"2022","journal-title":"JAMA Netw Open"},{"key":"2024060605400568000_2024.05.28.596304v1.7","doi-asserted-by":"publisher","DOI":"10.1136\/ijgc-2020-002072"},{"key":"2024060605400568000_2024.05.28.596304v1.8","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-013-2437-x"},{"key":"2024060605400568000_2024.05.28.596304v1.9","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.ejca.2022.03.014","article-title":"Overall survival is the lowest among young women with postpartum breast cancer","volume":"168","year":"2022","journal-title":"Eur J Cancer"},{"key":"2024060605400568000_2024.05.28.596304v1.10","unstructured":"Cancer Today. 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