Obesity and breast cancer mechanisms and therapeutic implications

Abstract

Obesity is a known risk factor for postmenopausal breast cancer, whereby factors produced by the adipose tissue are known to directly and indirectly affect tumour growth. It is now becoming increasingly clear that both obesity and cancer arise as a consequence of dysregulated metabolism, both in response to altered energy status and endocrine factors, and to intrinsic changes within cells. Moreover, both obesity and cancer lead to localised inflammation, whereby inflammatory cytokines and prostaglandins are produced by adipose tissue and tumour cells. Obesity is also a risk factor for type 2 diabetes, with a consequential increase in circulating insulin and insulin-like growth factor-I (IGF-I) known to promote tumour cell growth. Interestingly, these factors converge to increase aromatase expression within the breast and hence, estrogen production, thereby increasing the risk of breast cancer and the growth of breast tumour cells. Therapies aimed at treating obesity/diabetes are therefore attractive options for the treatment of postmenopausal breast cancer.