This study provides evidence that postmenopausal obesity enhances ERα positive breast cancer cell viability and growth via crosstalk between the ERα, PI3K/Akt and MAPK signaling pathways, suggesting that the addition of a PI3K/Akt/mTOR pathway inhibitor to aromatase inhibitor therapy may improve the clinical outcome of obese postmenopausal patients. This evidence concerns the gene ESR1 and breast cancer.