Obesity increases the risk for breast cancer after menopause. Animal studies reveal that obesity and ovariectomy-induced overfeeding converge to promote progesterone receptor (PR)-positive mammary tumors as shown by high nuclear PR immunohistochemical staining. Elevated PR expression positively correlated with tumor expression of glycolytic and lipogenic enzymes, glucose uptake, and proliferation markers. A similar relationship between PR expression and metabolic capacity was observed in tumors from postmenopausal women. Metformin treatment during the window of weight gain following ovariectomy caused PR downregulation and tumor regression. For details, see article by Giles and colleagues on page 6490.