4.6 Review

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

Journal

FRONTIERS IN ONCOLOGY
Volume 11, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2021.638918

Keywords

obesity; breast cancer; development; growth; estrogen

Categories

Funding

  1. NIH [R01 CA215797, 5 F31 CA236306-02]
  2. Anne Moore Breast Cancer Research Fund

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This review examines the interaction between obesity and breast cancer, focusing on estrogen, inflammatory mediators, and adipokines derived from breast adipose tissue, and how they are linked to oxidative stress, DNA damage, and pro-oncogenic transcriptional programs. Strategies targeting these factors for decreasing the risk of obesity-induced breast epithelial cell transformation and breast cancer development are evaluated for feasibility and efficacy.
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.

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