{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T16:41:37Z","timestamp":1764002497051,"version":"build-2065373602"},"reference-count":42,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T00:00:00Z","timestamp":1639094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Breast cancer (BC) treatments induce vitamin D (VD) insufficiency and bone metabolism changes, resulting in osteoporosis and skeletal morbidity risk. We report the results of a bicentric phase II trial (ClinicalTrials.gov Identifier: NCT04091178) on the safety and efficacy of high-dose oral VD supplementation for VD deficiency correction in 44 patients with early BC treated with adjuvant chemotherapies. Patients received one dose of 100,000 IU 25-OH VD every 3 weeks from day 1 of cycle 1 to day 1 of cycle 5. The primary endpoint was the percentage of patients achieving serum 25-OH VD concentration normalization on day 1 of cycle 6 (D1C6). Secondary endpoints were safety, VD and calcium parameters at baseline and during chemotherapy, and identification of predictive biomarkers of VD normalization on D1C6. On D1C6, 21 patients (47.7%, 95% CI: 33.0\u201362.8) achieved VD normalization. No VD-related clinical toxicity was reported. However, 13 patients (29.5%) presented asymptomatic grade 1 hypercalciuria, leading to interruption of the high-dose oral VD supplementation in 10, followed by a rapid reduction in serum VD concentration. No baseline clinical factor was predictive of VD normalization on D1C6. This high-dose VD supplementation appears safe and efficient in patients with early BC receiving adjuvant chemotherapy.<\/jats:p>","DOI":"10.3390\/nu13124429","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T01:29:33Z","timestamp":1639358973000},"page":"4429","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A Phase II Multicenter Trial on High-Dose Vitamin D Supplementation for the Correction of Vitamin D Insufficiency in Patients with Breast Cancer Receiving Adjuvant Chemotherapy"],"prefix":"10.3390","volume":"13","author":[{"given":"Elodie","family":"Chartron","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, ICM Val d\u2019Aurelle, Montpellier University, F-34298 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelly","family":"Firmin","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, ICM Val d\u2019Aurelle, Montpellier University, F-34298 Montpellier, France"},{"name":"Institut de Recherche en Canc\u00e9rologie de Montpellier (IRCM) INSERM U1194, F-34298 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9lia","family":"Touraine","sequence":"additional","affiliation":[{"name":"Biometrics Unit, Montpellier Cancer Institute, University of Montpellier, F-34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ang\u00e9lique","family":"Chapelle","sequence":"additional","affiliation":[{"name":"Institut de Cancerologie du Gard, Oncogard, F-30103 Nimes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Legouffe","sequence":"additional","affiliation":[{"name":"Institut de Cancerologie du Gard, Oncogard, F-30103 Nimes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lobna","family":"Rifai","sequence":"additional","affiliation":[{"name":"Clinical Research Department, ICM Val d\u2019Aurelle, Montpellier University, F-34298 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"St\u00e9phane","family":"Pouderoux","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, ICM Val d\u2019Aurelle, Montpellier University, F-34298 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lise","family":"Roca","sequence":"additional","affiliation":[{"name":"Biometrics Unit, Montpellier Cancer Institute, University of Montpellier, F-34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V\u00e9ronique","family":"D\u2019Hondt","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, ICM Val d\u2019Aurelle, Montpellier University, F-34298 Montpellier, France"},{"name":"Institut de Recherche en Canc\u00e9rologie de Montpellier (IRCM) INSERM U1194, F-34298 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7834-061X","authenticated-orcid":false,"given":"William","family":"Jacot","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, ICM Val d\u2019Aurelle, Montpellier University, F-34298 Montpellier, France"},{"name":"Institut de Recherche en Canc\u00e9rologie de Montpellier (IRCM) INSERM U1194, F-34298 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1200\/JCO.2000.18.7.1570","article-title":"Osteoporosis Due to Cancer Treatment: Pathogenesis and Management","volume":"18","author":"Pfeilschifter","year":"2000","journal-title":"J. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1001\/archinte.165.5.552","article-title":"Fracture Risk Among Breast Cancer Survivors: Results from the Women\u2019s Health Initiative Observational Study","volume":"165","author":"Chen","year":"2005","journal-title":"Arch. Intern. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s11912-003-0086-7","article-title":"Osteoporosis in women with breast cancer","volume":"5","author":"Mincey","year":"2003","journal-title":"Curr. Oncol. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1200\/JCO.1997.15.4.1341","article-title":"Chemical castration induced by adjuvant cyclophosphamide, methotrexate, and fluorouracil chemotherapy causes rapid bone loss that is reduced by clodronate: A randomized study in premenopausal breast cancer patients","volume":"15","author":"Saarto","year":"1997","journal-title":"J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s12609-018-0295-6","article-title":"Bone-Modifying Agents in Early-Stage and Advanced Breast Cancer","volume":"10","author":"Heeke","year":"2018","journal-title":"Curr. Breast Cancer Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/S0002-9343(02)01091-4","article-title":"Vitamin D insufficiency among free-living healthy young adults","volume":"112","author":"Tangpricha","year":"2002","journal-title":"Am. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3757","DOI":"10.1200\/JCO.2008.20.0725","article-title":"Prognostic Effects of 25-Hydroxyvitamin D Levels in Early Breast Cancer","volume":"27","author":"Goodwin","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1093\/ajcn\/88.1.133","article-title":"Vitamin D insufficiency in a multiethnic cohort of breast cancer survivors","volume":"88","author":"Neuhouser","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1093\/annonc\/mdw145","article-title":"Impact of a tailored oral vitamin D supplementation regimen on serum 25-hydroxyvitamin D levels in early breast cancer patients: A randomized phase III study","volume":"27","author":"Jacot","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1093\/jnci\/djm204","article-title":"Prospective Study of Serum Vitamin D and Cancer Mortality in the United States","volume":"99","author":"Freedman","year":"2007","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1136\/jcp.2006.042747","article-title":"Serum 25-hydroxyvitamin D levels in early and advanced breast cancer","volume":"59","author":"Palmieri","year":"2006","journal-title":"J. Clin. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Viala, M., Chiba, A., Thezenas, S., Delmond, L., Lamy, P.-J., Mott, S.L., Schroeder, M.C., Thomas, A., and Jacot, W. (2018). Impact of vitamin D on pathological complete response and survival following neoadjuvant chemotherapy for breast cancer: A retrospective study. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4686-x"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"R980","DOI":"10.1186\/bcr1332","article-title":"25-Hydroxyvitamin D31\u03b1-hydroxylase expression in breast cancer and use of non-1\u03b1-hydroxylated vitamin D analogue","volume":"7","author":"Segersten","year":"2005","journal-title":"Breast Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/978-3-642-55580-0_2","article-title":"Current Understanding of the Function of the Nuclear Vitamin D Receptor in Response to Its Natural and Synthetic Ligands","volume":"164","author":"Carlberg","year":"2003","journal-title":"Vitam. D Analog. Cancer Prev. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/j.1432-0436.2006.00131.x","article-title":"Vitamin D regulates the phenotype of human breast cancer cells","volume":"75","author":"Aguilera","year":"2007","journal-title":"Differentiation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s002800000251","article-title":"The vitamin D3 analog, ILX-23-7553, enhances the response to adriamycin and irradiation in MCF-7 breast tumor cells","volume":"47","author":"Chaudhry","year":"2001","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_17","first-page":"1043","article-title":"Calcitriol (1,25-dihydroxycholecalciferol) enhances paclitaxel antitumor activity in vitro and in vivo and accelerates paclitaxel-induced apoptosis","volume":"7","author":"Hershberger","year":"2001","journal-title":"Clin. Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1200\/JCO.2016.70.7257","article-title":"Use of Adjuvant Bisphosphonates and Other Bone-Modifying Agents in Breast Cancer: A Cancer Care Ontario and American Society of Clinical Oncology Clinical Practice Guideline","volume":"35","author":"Fletcher","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1210\/jc.2011-0385","article-title":"Evaluation, Treatment, and Prevention of Vitamin D Deficiency: An Endocrine Society Clinical Practice Guideline","volume":"96","author":"Holick","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1093\/jnci\/djn360","article-title":"Calcium Plus Vitamin D Supplementation and the Risk of Breast Cancer","volume":"100","author":"Chlebowski","year":"2008","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1093\/ajcn\/85.6.1586","article-title":"Vitamin D and calcium supplementation reduces cancer risk: Results of a randomized trial","volume":"85","author":"Lappe","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1200\/JCO.2008.19.6162","article-title":"High Prevalence of Vitamin D Deficiency Despite Supplementation in Premenopausal Women with Breast Cancer Undergoing Adjuvant Chemotherapy","volume":"27","author":"Crew","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s10549-011-1415-4","article-title":"The effect of various vitamin D supplementation regimens in breast cancer patients","volume":"127","author":"Peppone","year":"2011","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1007\/s00198-012-1944-7","article-title":"Effect of oral cholecalciferol 2,000 versus 5,000 IU on serum vitamin D, PTH, bone and muscle strength in patients with vitamin D deficiency","volume":"24","author":"Diamond","year":"2012","journal-title":"Osteoporos. Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s10549-009-0495-x","article-title":"Effect of vitamin D supplementation on serum 25-hydroxy vitamin D levels, joint pain, and fatigue in women starting adjuvant letrozole treatment for breast cancer","volume":"119","author":"Khan","year":"2009","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.clbc.2017.12.001","article-title":"Serum Vitamin D Levels Affect Pathologic Complete Response in Patients Undergoing Neoadjuvant Systemic Therapy for Operable Breast Cancer","volume":"18","author":"Chiba","year":"2018","journal-title":"Clin. Breast Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1016\/j.ejca.2014.02.026","article-title":"Changes in serum hydroxyvitamin D levels of breast cancer patients during tamoxifen treatment or chemotherapy in premenopausal breast cancer patients","volume":"50","author":"Kim","year":"2014","journal-title":"Eur. J. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"134","DOI":"10.4048\/jbc.2018.21.2.134","article-title":"Association between Changes in Serum 25-Hydroxyvitamin D Levels and Survival in Patients with Breast Cancer Receiving Neoadjuvant Chemotherapy","volume":"21","author":"Kim","year":"2018","journal-title":"J. Breast Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1080\/01635581.2018.1559938","article-title":"Changes in Circulating Levels of 25-hydroxyvitamin D3 in Breast Cancer Patients Receiving Chemotherapy","volume":"71","author":"Kok","year":"2019","journal-title":"Nutr. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/ijc.1568","article-title":"Prediction of response to docetaxel by CYP3A4 mRNA expression in breast cancer tissues","volume":"97","author":"Miyoshi","year":"2002","journal-title":"Int. J. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Viala, M., Firmin, N., Touraine, C., Pouderoux, S., Metge, M., Rifai, L., Romieu, G., de Forges, H., Roca, L., and Guiu, S. (2021). Changes in vitamin D and calcium metabolism markers in patients undergoing adjuvant chemotherapy for breast cancer. BMC Cancer, 21.","DOI":"10.1186\/s12885-021-08563-4"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1093\/ajcn\/73.2.288","article-title":"Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level","volume":"73","author":"Vieth","year":"2001","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/0026-0495(83)90221-4","article-title":"Importance of increased urinary calcium excretion in the development of secondary hyperparathyroidism of patients under glucocorticoid therapy","volume":"32","author":"Suzuki","year":"1983","journal-title":"Metabolism"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"338","DOI":"10.3109\/0886022X.2011.648596","article-title":"The Course of Hypercalciuria and Related Markers of Bone Metabolism Parameters Associated with Corticosteroid Treatment","volume":"34","author":"Duzen","year":"2012","journal-title":"Ren. Fail."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/S0022-3476(89)80138-6","article-title":"Mineral homeostasis and bone mass in children treated for acute lymphoblastic leukemia","volume":"114","author":"Atkinson","year":"1989","journal-title":"J. Pediatr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1475-2891-10-3","article-title":"The role of salt abuse on risk for hypercalciuria","volume":"10","author":"Damasio","year":"2011","journal-title":"Nutr. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1210\/jcem-70-4-1007","article-title":"Effects of Dietary Carbohydrates on Metabolism of Calcium and Other Minerals in Normal Subjects and Patients with Noninsulin-Dependent Diabetes Mellitus","volume":"70","author":"Garg","year":"1990","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1210\/jcem-35-2-261","article-title":"Gastrointestinal Calcium Absorption in Nephrolithiasis","volume":"35","author":"Pak","year":"1972","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Hu, H., Zhang, J., Lu, Y., Zhang, Z., Qin, B., Gao, H., Wang, Y., Zhu, J., Wang, Q., and Zhu, Y. (2017). Association between Circulating Vitamin D Level and Urolithiasis: A Systematic Review and Meta-Analysis. Nutrients, 9.","DOI":"10.3390\/nu9030301"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jsbmb.2018.12.002","article-title":"Adverse events from large dose vitamin D supplementation taken for one year or longer","volume":"188","author":"Malihi","year":"2019","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jsbmb.2017.07.025","article-title":"Vitamin D and breast cancer: Past and present","volume":"177","author":"Welsh","year":"2018","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_42","first-page":"110964","article-title":"Role of vitamin D3 in selected malignant neoplasms","volume":"79\u201380","author":"Markowska","year":"2020","journal-title":"Nutrients"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/12\/4429\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:45:21Z","timestamp":1760168721000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/12\/4429"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,10]]},"references-count":42,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["nu13124429"],"URL":"https:\/\/doi.org\/10.3390\/nu13124429","relation":{},"ISSN":["2072-6643"],"issn-type":[{"type":"electronic","value":"2072-6643"}],"subject":[],"published":{"date-parts":[[2021,12,10]]}}}