Macrophages in obesity-related breast cancer: mechanistic insights and therapeutic opportunities

Obesity has emerged as a global public health crisis, significantly increasing susceptibility to malignancies, including breast cancer. In the context of Obesity-Related Breast Cancer (ORBC), the abundant adipose tissue in the mammary gland profoundly reshapes the tumor microenvironment (TME). Whereas obesity drives chronic, low-grade inflammation through pro-inflammatory M1 adipose tissue macrophages (ATMs), tumor-associated macrophages (TAMs) acquire a predominantly immunosuppressive M2 phenotype that promotes angiogenesis, immune evasion, and treatment resistance. This review examines macrophage ontogeny, polarization, and functional heterogeneity in ORBC, highlighting how obesity-induced cytokines (e.g. TNF-α, IL-6), reactive oxygen species, and metabolic reprogramming collectively reshape the TME to foster tumor initiation, progression, and metastasis. We further evaluate emerging therapeutic strategies—such as CSF-1R inhibitors, PD-1/PD-L1 checkpoint blockade, and CAR-macrophage immunotherapies—that target macrophages recruitment, polarization, and immunometabolic pathways in ORBC.