Metabolic pathways in obesity-related breast cancer

Obesity is linked to dysregulated cellular energetics in neoplastic and non-neoplastic cells in the tumour microenvironment. Here, Brown discusses the interdependence of metabolic pathways of oestrogen production in breast tissue and the obesity-related mechanisms that promote breast cancer growth. This Review focuses on the mechanistic evidence for a link between obesity, dysregulated cellular metabolism and breast cancer. Strong evidence now links obesity with the development of 13 different types of cancer, including oestrogen receptor-positive breast cancer in postmenopausal women. A number of local and systemic changes are hypothesized to support this relationship, including increased circulating levels of insulin and glucose as well as adipose tissue-derived oestrogens, adipokines and inflammatory mediators. Metabolic pathways of energy production and utilization are dysregulated in tumour cells and this dysregulation is a newly accepted hallmark of cancer. Dysregulated metabolism is also hypothesized to be a feature of non-neoplastic cells in the tumour microenvironment. Obesity-associated factors regulate metabolic pathways in both breast cancer cells and cells in the breast microenvironment, which provides a molecular link between obesity and breast cancer. Consequently, interventions that target these pathways might provide a benefit in postmenopausal women and individuals with obesity, a population at high risk of breast cancer.