Breast cancer microenvironment and obesity: challenges for therapy

Women with obesity who develop breast cancer have a worsened prognosis with diminished survival rates and increased rates of metastasis. Obesity is also associated with decreased breast cancer response to endocrine and chemotherapeutic treatments. Studies utilizing multiple in vivo models of obesity as well as human breast tumors have enhanced our understanding of how obesity alters the breast tumor microenvironment. Changes in the complement and function of adipocytes, adipose-derived stromal cells, immune cells, and endothelial cells and remodeling of the extracellular matrix all contribute to the rapid growth of breast tumors in the context of obesity. Interactions of these cells enhance secretion of cytokines and adipokines as well as local levels of estrogen within the breast tumor microenvironment that promote resistance to multiple therapies. In this review, we will discuss our current understanding of the impact of obesity on the breast tumor microenvironment, how obesity-induced changes in cellular interactions promote resistance to breast cancer treatments, and areas for development of treatment interventions for breast cancer patients with obesity.