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.
Strong evidence links obesity to the development of 13 types of cancer, including oestrogen receptor-positive breast cancer in postmenopausal women.
Metabolic pathways involving PI3K–AKT, HIF1α, LKB1–AMPK and p53 are key regulators of breast cancer cell metabolism and growth.
Obesity-associated factors drive metabolic alterations in both breast cancer cells and cells of the breast microenvironment that support tumour growth.
Therapies that target metabolic pathways might prove effective at treating and preventing breast cancer via effects on cancer cells, the tumour microenvironment and whole-body metabolism.
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Research work by K.A.B. is supported by NIH grant R01 CA215797 and the Anne Moore Breast Cancer Research Fund.
The author declares no competing interests.
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Brown, K.A. Metabolic pathways in obesity-related breast cancer. Nat Rev Endocrinol (2021). https://doi.org/10.1038/s41574-021-00487-0