Epidemiological studies have shown that before the menopause, obesity is either not associated with most molecular subtypes of breast cancer, or, in younger premenopausal women, actually has a protective effect; moreover, the tumors that do develop are less likely to be ER/PR-positive (reviewed by Rose and Vona-Davis, [51]). Here, ESR1 is linked to obesity due to melanocortin 4 receptor deficiency.