Mammary adipose dysfunction in the dual epidemic of obesity and breast cancer

Breast cancer (BC) is one of the leading causes of death among women, with obesity being a significant factor. Mammary adipose tissue (MAT) dysfunction in obesity creates a tumor-supportive environment, leading to increased risk. In obesity, MAT undergoes significant changes, including increased adiposity, chronic inflammation, aromatase overexpression, insulin resistance, and altered adipokine signaling, collectively fostering a protumorigenic microenvironment. The interaction between adipocytes and cancer cells further exacerbates BC progression through metabolic crosstalk and immune evasion. This review examines the role of MAT dysfunction in BC incidence and progression, in obesity. Interestingly, obesity appears to have a paradoxical effect on BC risk, offering a potentially protective role in premenopausal women, but increased risk in postmenopausal women, primarily due to differences in estrogen levels. Addressing the metabolic, inflammatory, and hormonal abnormalities in obese MAT can aid in enabling the development of precision therapies that reduce BC risk and improve treatment outcomes in obese patients.