title: The Interactions of Obesity, Inflammation and Insulin Resistance in Breast Cancer.
abstract: Obese postmenopausal women have an increased breast cancer risk, the principal mechanism for which is elevated estrogen production by adipose tissue; also, regardless of menstrual status and tumor estrogen dependence, obesity is associated with biologically aggressive breast cancers. Type 2 diabetes has a complex relationship with breast cancer risk and outcome; coexisting obesity may be a major factor, but insulin itself induces adipose aromatase activity and estrogen production and also directly stimulates breast cancer cell growth and invasion. Adipose tissue inflammation occurs frequently in obesity and type 2 diabetes, and proinflammatory cytokines and prostaglandin E2 produced by cyclooxygenase-2 in the associated infiltrating macrophages also induce elevated aromatase expression. In animal models, the same proinflammatory mediators, and the chemokine monocyte chemoattractant protein-1, also stimulate tumor cell proliferation and invasion directly and promote tumor-related angiogenesis. We postulate that chronic adipose tissue inflammation, rather than body mass index-defined obesity per se, is associated with an increased risk of type 2 diabetes and postmenopausal estrogen-dependent breast cancer. Also, notably before the menopause, obesity and type 2 diabetes, or perhaps the associated inflammation, promote estrogen-independent, notably triple-negative, breast cancer development, invasion and metastasis by mechanisms that may involve macrophage-secreted cytokines, adipokines and insulin.
authors.affiliation: Mary Babb Randolph Cancer Center,West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. davidrosemd@hotmail.com.
authors.forename: David P
authors.initials: DP
authors.lastname: Rose
authors.affiliation: Mary Babb Randolph Cancer Center,West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. pjgracheck@mix.wvu.edu.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Gracheck
authors.affiliation: Mary Babb Randolph Cancer Center,West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. lvdavis@hsc.wvu.edu.|Department of Surgery, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. lvdavis@hsc.wvu.edu.
authors.forename: Linda
authors.initials: L
authors.lastname: Vona-Davis
keywords: breast cancer; inflammation; insulin