ESR1 and neoplasm: In this respect, our present findings suggest that in the sub-population of obese postmenopausal ER+BC patients (especially in the face of increased estrogen production in fat depots [13,16,20,29,32]), upregulation of ERα expression by the tumor may promote BC progression and render it less sensitive to standard therapeutic approaches (i.e., estrogen deprivation (Figure 4), and ionizing radiation (Supplementary Figure S1C)).