To address this gap in our literature, here for the first time, we investigated whether VDR polymorphisms (ApaI, TaqI, FokI, BsmI and Cdx2) could affect breast cancer survivors’ responses to vitamin D3 supplementation through potential cancer biomarkers, including E-cadherin, matrix metallopeptidase 9 (MMP9), interferon β (IFNβ), soluble intercellular adhesion molecule-1 (s-ICAM-1), soluble vascular cell adhesion molecule-1 (s-VCAM-1), tumor necrosis factorα (TNFα), interleukin 6 (IL6), plasminogen activator inhibitor-1 (PAI-1), and human high sensitivity C-reactive protein (hs-CRP). This evidence concerns the gene SERPINE1 and breast cancer.