Using Wnt-1 p53+/+ and Wnt-1 p53+/− mouse models of postmenopausal basal-like breast cancer, we provide evidence that a DIO regimen (relative to control diet and regardless of tumoral p53 genotype): i) promotes mammary tumor progression, more severe tumor pathology, EMT, and loss of ERα protein expression; and ii) suppresses tumoral p53 and p21 protein expression in association with increased expression of the negative regulator of p53, miR-504. The gene discussed is TP53; the disease is neoplasm.