ESR1 and obesity due to melanocortin 4 receptor deficiency: Surprisingly, the latter finding is potentially inconsistent with the notion that among postmenopausal women, obesity is generally associated with higher plasma levels of estradiol from adipose tissue [31] and greater risk of ER+ (primarily Luminal A) breast cancer [32,33], and suggests that even if higher circulating estradiol is available in postmenopausal women, the tumor itself may be less responsive to endogenous estrogen depending on level of obesity.