Obese Adipose Tissue as a Driver of Breast Cancer Growth and Development: Update and Emerging Evidence.

Priya Bhardwaj,Kristy A Brown

doi:10.3389/fonc.2021.638918

Abstract

Obesity is an established risk factor for breast cancer growth and progression. A number of advances have been made in recent years revealing new insights into this link. Early events in breast cancer development involve the neoplastic transformation of breast epithelial cells to cancer cells. In obesity, breast adipose tissue undergoes significant hormonal and inflammatory changes that create a mitogenic microenvironment. Many factors that are produced in obesity have also been shown to promote tumorigenesis. Given that breast epithelial cells are surrounded by adipose tissue, the crosstalk between the adipose compartment and breast epithelial cells is hypothesized to be a significant player in the initiation and progression of breast cancer in individuals with excess adiposity. The present review examines this crosstalk with a focus on obese breast adipose-derived estrogen, inflammatory mediators and adipokines, and how they are mechanistically linked to breast cancer risk and growth through stimulation of oxidative stress, DNA damage, and pro-oncogenic transcriptional programs. Pharmacological and lifestyle strategies targeting these factors and their downstream effects are evaluated for feasibility and efficacy in decreasing the risk of obesity-induced breast epithelial cell transformation and consequently, breast cancer development.

Highlights

Breast cancer is the second most common cancer diagnosed in women in the U.S and the most common cancer among women worldwide, accounting for an estimated 627,000 deaths in 2018 [1, 2]
While lifestyle interventions that reduce weight have been reported to be effective at ameliorating the adipose tissue dysfunction associated with obesity and reducing breast cancer risk, major limitations of lifestyle approaches include the difficulty in adherence to diet and/or exercise regimens and the lack of sustainability of long-term weight loss [145, 146]
Abundant evidence demonstrates the importance of the crosstalk between obese breast adipose tissue and neighboring normal and neoplastic breast epithelial cells

Summary

Introduction

Breast cancer is the second most common cancer diagnosed in women in the U.S and the most common cancer among women worldwide, accounting for an estimated 627,000 deaths in 2018 [1, 2]. Leptin was shown to transactivate ERa via signaling through ERK1/ERK2 in MCF7 breast cancer cells [72] and increase estrogen production in the local microenvironment by stimulating aromatase expression in ASCs [73,74,75] (Figure 2).

Results

Conclusion