Obesity and Breast Cancer: A Case of Inflamed Adipose Tissue

Ryan Kolb, Weizhou Zhang, Ryan Kolb, Weizhou Zhang

Abstract

Obesity is associated with an increased risk of estrogen receptor-positive breast cancer in postmenopausal women and a worse prognosis for all major breast cancer subtypes regardless of menopausal status. While the link between obesity and the pathogenesis of breast cancer is clear, the molecular mechanism of this association is not completely understood due to the complexity of both obesity and breast cancer. The aim of this review is to highlight the association between obesity and breast cancer and discuss the literature, which indicates that this association is due to chronic adipose tissue inflammation. We will discuss the epidemiological data for the association between breast cancer incidence and progression as well as the potential molecular mechanisms for this association. We will focus on the role of inflammation within the adipose tissue during the pathogenesis of breast cancer. A better understanding of how obesity and adipose tissue inflammation affects the pathogenesis of breast cancer will lead to new strategies to reduce breast cancer risk and improve patient outcomes for obese patients.

Keywords: breast cancer; inflammation; obesity.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Obesity-associated adipose tissue inflammation. Excess energy intake during obesity leads to adipocyte hypertrophy and cell death. This leads to the secretion of inflammatory cytokines and chemokines, which induce the recruitment and polarization of macrophages. Macrophages surround dead adipocytes, forming a crown-like structure (CLS) and secreting inflammatory cytokines. Adipocyte hypertrophy also leads to an increase in leptin and a decrease in adiponectin, which further induces the expression of inflammatory cytokines.
Figure 2
Figure 2
Mechanisms of obesity-driven breast cancer. Obesity leads to adipocyte hypertrophy, which induces the secretion of inflammatory cytokines, chemokines, and leptin. These adipokines then induce the recruitment and polarization of macrophages. Macrophages secrete inflammatory cytokines, which can act directly to promote breast cancer, act on adipocytes to increase the expression of aromatase and estrogen production, and induce the expression of pro-angiogenic factors. Adipose tissue inflammation also promotes the development of insulin resistance, leading to increased insulin and insulin-like growth factor (IGF). Insulin and IGF can directly promote breast cancer. Leptin from adipocytes can also directly act on cancer cells. Obesity leads to a decrease in adiponectin, which inhibits breast cancer.

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