FGF1 supports metabolic reprogramming through the estrogen receptor in endocrine-resistant and obesity-associated breast cancer

Obesity is associated with elevated breast cancer risk and with breast cancer-specific mortality, particularly for people with estrogen receptor (ER) positive tumors. Body mass index (BMI) is commonly used to define obesity, but it may not be the best predictor of breast cancer risk or prognosis on an individual level. Adult weight gain is an independent prognostic indicator of breast cancer risk, and many patients undergoing cancer treatment experience the side effect of weight gain. Our previous work described a murine model of obesity, ER-positive breast cancer, and weight gain, and identified fibroblast growth factor receptor (FGFR) as a potential driver of tumor progression in some cases. During adipose tissue expansion, the FGF1 ligand is produced by hypertrophic adipocytes as a stimulus to stromal preadipocytes that proliferate and differentiate to provide additional lipid storage capacity. In the breast adipose tissue, FGF1 production may stimulate cancer cell proliferation and tumor progression.