The obesity-breast cancer link: a multidisciplinary perspective

Abstract

Obesity, exceptionally prevalent in the USA, promotes the incidence and progression of numerous cancer types including breast cancer. Complex, interacting metabolic and immune dysregulation marks the development of both breast cancer and obesity. Obesity promotes chronic low-grade inflammation, particularly in white adipose tissue, which drives immune dysfunction marked by increased pro-inflammatory cytokine production, alternative macrophage activation, and reduced T cell function. Breast tissue is predominantly composed of white adipose, and developing breast cancer readily and directly interacts with cells and signals from adipose remodeled by obesity. This review discusses the biological mechanisms through which obesity promotes breast cancer, the role of obesity in breast cancer health disparities, and dietary interventions to mitigate the adverse effects of obesity on breast cancer. We detail the intersection of obesity and breast cancer, with an emphasis on the shared and unique patterns of immune dysregulation in these disease processes. We have highlighted key areas of breast cancer biology exacerbated by obesity, including incidence, progression, and therapeutic response. We posit that interception of obesity-driven breast cancer will require interventions that limit protumor signaling from obese adipose tissue and that consider genetic, structural, and social determinants of the obesity-breast cancer link. Finally, we detail the evidence for various dietary interventions to offset obesity effects in clinical and preclinical studies of breast cancer. In light of the strong associations between obesity and breast cancer and the rising rates of obesity in many parts of the world, the development of effective, safe, well-tolerated, and equitable interventions to limit the burden of obesity on breast cancer are urgently needed.

Keywords: Adipose; Breast cancer; Diet; Health disparities; Immune; Obesity.

Fig. 1

The impact of obesity on the tumor microenvironment. White adipose tissue from an obese host is composed of hypertrophied adipocytes, some of which become necrotic and induce formation of crown-like structures. Adipose tissue inflammation is furthered by M1-like and metabolically activated macrophages. Tumors developing adjacent to obese adipose tissue receive numerous inflammatory and metabolic signals from adipose and are marked by immunosuppressed tumor microenvironment with ineffective tumor-infiltrating lymphocytes and immunosuppressive M2-like macrophage polarization. Adipose tissue further contributes to the tumor microenvironment via recruitment and transdifferentiation of cancer-associated fibroblasts from mesenchymal stem cells, and adipocyte-derived fibroblasts from adipocytes