Effects of cholecalciferol supplementation on serum angiogenic biomarkers in breast cancer patients treated with tamoxifen: A controlled randomized clinical trial

• Published in: Nutrition (Burbank, Los Angeles County, Calif.) Vol. 72; p. 110656
• Main Authors: Shahvegharasl, Zahra, Pirouzpanah, Saeed, Mahboob, Soltan Ali, Montazeri, Vahid, Adili, Ali, Asvadi, Iraj, Sanaat, Zohreh, Esfehani, Ali, Pirouzpanah, Seyed-Sajjad, Mesgari, Mehran
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2020; Elsevier Limited
• Subjects: Adult; Angiogenesis; Angiopoietin; Angiopoietin-2 - blood; Antineoplastic Agents, Hormonal; Biomarkers; Biomarkers - blood; Blood vessels; Breast cancer; Breast Neoplasms - blood; Breast Neoplasms - therapy; C-reactive protein; Cancer therapies; Cell cycle; Cholecalciferol; Cholecalciferol - administration & dosage; Clinical trials; Dietary Supplements; Double-Blind Method; Enzyme-linked immunosorbent assay; Female; Growth factors; Humans; Hypoxia; Hypoxia-Inducible Factor 1 - blood; Infiltration; Intervention; Kinases; Lymphatic system; Medical records; Medical research; Metastases; Metastasis; Middle Aged; Patients; Pilot Projects; Postmenopause - blood; Premenopause - blood; Protein expression; Proteins; Research Design; Serum levels; Subgroups; Tamoxifen; Tamoxifen - therapeutic use; Tumors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - blood; Vitamin D; Vitamin deficiency; Vitamins - administration & dosage; Iran; Intervention; Angiogenesis; Breast cancer; Tamoxifen; Cholecalciferol
• ISSN: 0899-9007; 1873-1244
• DOI: 10.1016/j.nut.2019.110656

•Cholecalciferol led to reduced serum angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF)-A in premenopausal patients with breast cancer.•Cholecalciferol increased the serum Ang-2 and VEGF-A in postmenopausal participants.•Of participants lacking pathologic vascular invasion, cholecalciferol reduced serum Ang-2.•In the absence of lymphovascular invasion, cholecalciferol increased serum hypoxia-inducible factor-1. The aim of this study was to investigate the effects of cholecalciferol supplementation on serum levels of angiogenic parameters in patients with breast cancer (BC) who were treated with tamoxifen. This was a pilot-based, randomized, triple-blind, placebo-controlled clinical trial with 52 patients with BC randomly assigned to either an intervention group receiving weekly 50 000 IU cholecalciferol or a placebo group for 8 wk. At baseline and at end of study, serum levels of angiogenic growth factors such as vascular endothelial growth factor (VEGF)-A, angiopoietin (Ang)-2, hypoxia-inducible factor (Hif)-1, and high-sensitivity C-reactive protein were measured by enzyme-linked immunosorbent assay. Every 4 wk, a completed 3-d, 24-h dietary record and daily sunlight exposure checklist were collected and anthropometric variables were measured. The ultimate number of participants in each arm was 22 for analyses. For premenopausal women, cholecalciferol supplementation resulted in a significant decrease in serum levels of Ang-2 and VEGF-A after 8 wk of treatment (P < 0.05). In the absence of vascular invasion, supplementation led to a significant decrease in Ang-2 levels compared with the placebo group (P < 0.05). Supplementation caused significant increases in Hif-1 in patients diagnosed with the infiltration of tumors into vascular or lymphatic vessels (P < 0.05). Cholecalciferol supplementation achieved sufficient efficacy among patients with BC taking tamoxifen and could be effective in the reduction of angiogenic biomarkers particularly dependent on the infiltration status of the tumor to vessels. Further studies with larger subgroups should be investigated.