Obesity, Inflammation, and Postmenopausal Breast Cancer: Therapeutic Implications

Figure 1

Different mechanisms of estrogen dependence for hormone-related breast cancer in pre- and postmenopausal women. In premenopausal women, the main site of synthesis of estrogen is the ovary. In postmenopausal women, adipose tissue is the main source of the circulating estrogens. Adipose tissue produces the enzymes aromatase; therefore, in obese women, there is an increased conversion of the androgens androstenedione and testosterone into the estrogens: oestrone and oestradiol, respectively, by aromatase. Moreover, obesity, being associated with metabolic syndrome, results in increasingly circulating levels of insulin and insulin-like growth factor, which, by acting as mitogens for epithelial breast cells, stimulate their neoplastic degeneration. Moreover, adipocytes produce several “adipokines” such as leptin and inflammatory cytokines which can influence aromatase activity and estrogen-dependent cell proliferation. IGF, insulin growth factor; IL, interleukin; TNF-α, tumour necrosis factor-α; Lp, leptin; E, estradiol; A, aromatase.