Effect of cholecalciferol supplementation on serum levels of vascular endothelial growth factor-A, angiopoietin-2, hypoxia inducible factor-1 and high-sensitivity c-reactive protein in breast cancer patients consuming tamoxifen: a controlled randomized clinical trial

Abstract

Introduction: Breast cancer (BC) is one of the main public healthy concern worldwild. Cholecalciferol can inhibit angiogenesis and be considered as an adjuvant therapy with hormone therapy. The purpose of this clinical trial was to study the effect of cholecalciferol supplementation on serum levels of angiogenic parameters in women detected with breast cancer who were consuming tamoxifen. Methods: In the present randomized, placebo-controlled clinical trial, 44 invasive ductal BC patients with pathological confirmed malignancy were enrolled. Participants, researcher who carried out the trial protocol, and laboratory assessors were blinded to the treatment assignments. The intervention group received 50000 IU cholecalciferol weekly and the placebo group took a placebo pearl per week for 8 weeks. At baseline and endpoint of the study serum levels of angiogenic growth factors such as vascular endothelial growth factor- A (VEGF-A), angiopoietin-2 (Ang-2), high sensitivy Creactive protein (HSCRP) and hypoxia inducible factor- 1 (Hif-1) were measured. Results: In this study, cholecalciferol deficiency (<30 ng/ml) was observed in 72.7% of this sample population. Cholecalciferol supplementation showed significant reduction in Ang-2 and VEGF-A levels significantly among pre-menopause women after 8 weeks (P<0.05). However, in menopause women significant increase of Ang-2 and VEGF-A in cholecalciferol group was more notable compared to placebo group. In patients with ER (-) cholecalciferol could decrease Ang-2 levels significant while increase in placebo group (P<0.05). Among ER- group, significant decrease in Ang-2/VEGF-A levels in cholecalciferol group compared to placebo group was observed (P<0.05). Of those who had HER-2(+), significant, decrease of HSCRP in cholecalciferol group was seen, while HSCRP levels increased significantly in placebo group (P<0.05). HSCRP levels increased significantly in patients with tumor grade II as well (p<0.05). Conclusion: Results of this clinical trial study in BC women showed that cholecalciferol supplementation could decrease serum levels of Ang-2, VEGF-A and HSCRP in patients with negative hormonal receptors. Therby, the absence of protein expression of the hormon receptor cause poor prognosis of BC and inhibitory effects of cholecalciferol on angiogenesis biomarkers is considirable.