Obesity likely contributes via two mechanisms: (1) adipose tissue-secreted adipokines alter estrogen receptor expression in breast parenchyma, disrupting hormonal homeostasis (6); (2) excessive adipose remodeling induces tissue hypoxia, triggering local inflammatory cascades characterized by pro-inflammatory cytokine upregulation (7). Here, ESR1 is linked to obesity due to melanocortin 4 receptor deficiency.