The connection between obesity and ER-positive BC in post-menopausal women is likely attributable to two main interrelated factors that will be a key focus of this review, including: (i) increased adipose tissue (AT) mass and the associated increase in inflammatory mediator production (both locally and systemically); and (ii) elevated AT aromatase activation, which is up-regulated by inflammatory mediators and drives aberrant estrogen production within the AT, thereby promoting BC tumorigenesis. This evidence concerns the gene CYP19A1 and obesity due to melanocortin 4 receptor deficiency.