期刊
CANCER AND METASTASIS REVIEWS
卷 41, 期 3, 页码 627-647出版社
SPRINGER
DOI: 10.1007/s10555-022-10031-9
关键词
Obesity; Breast cancer; Cancer-associated fibroblasts; Adipocytes; Macrophages; Extracellular matrix
类别
资金
- NIH [R01 CA227542, F31 CA247265]
- Howard Hughes Medical Institute through the James H. Gilliam Fellowships for Advanced Study program
Obese women with breast cancer have poorer prognosis and increased metastasis rates. Obesity also affects the response of breast cancer to endocrine and chemotherapeutic treatments. Changes in the breast tumor microenvironment caused by obesity promote rapid tumor growth and resistance to therapies.
Women with obesity who develop breast cancer have a worsened prognosis with diminished survival rates and increased rates of metastasis. Obesity is also associated with decreased breast cancer response to endocrine and chemotherapeutic treatments. Studies utilizing multiple in vivo models of obesity as well as human breast tumors have enhanced our understanding of how obesity alters the breast tumor microenvironment. Changes in the complement and function of adipocytes, adipose-derived stromal cells, immune cells, and endothelial cells and remodeling of the extracellular matrix all contribute to the rapid growth of breast tumors in the context of obesity. Interactions of these cells enhance secretion of cytokines and adipokines as well as local levels of estrogen within the breast tumor microenvironment that promote resistance to multiple therapies. In this review, we will discuss our current understanding of the impact of obesity on the breast tumor microenvironment, how obesity-induced changes in cellular interactions promote resistance to breast cancer treatments, and areas for development of treatment interventions for breast cancer patients with obesity.
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