Obesity and Breast Cancer: The Role of Crown-Like Structures in Breast Adipose Tissue in Tumor Progression, Prognosis, and Therapy

Abstract

Obesity is associated with increased risk and aggressiveness of many types of cancer. Women with obesity and breast cancer are more likely to be diagnosed with larger and higher-grade tumors and have higher incidence of metastases than lean individuals. Increasing evidence indicates that obesity includes systemic, chronic low-grade inflammation, and that adipose tissue can act as an important endocrine site, secreting a variety of substances that may regulate inflammation, immune response, and cancer predisposition. Obesity-associated inflammation appears to be initially mediated by macrophage infiltration into adipose tissue. Macrophages can surround damaged or necrotic adipocytes, forming “crown-like” structures (CLS). CLS are increased in breast adipose tissue from breast cancer patients and are more abundant in patients with obesity conditions. Moreover, the CLS index-ratio from individuals with obesity seems to influence breast cancer recurrence rates and survival. In this review, we discuss the most recent cellular and molecular mechanisms involved in CLS establishment in the white adipose tissue of women with obesity and their implications for breast cancer biology. We also explain how CLS influence the tumor microenvironment and affect breast cancer behavior. Targeting breast adipose tissue CLS can be a crucial therapeutic tool in cancer treatment, especially in patients with obesity.