Given the common signaling cascades involved in AGE pathogenesis and ERα regulation, we examined the ability of AGEs to augment ERα phosphorylation and tamoxifen resistance, and tested the ability of a defined lifestyle intervention program to lower AGE levels in overweight/obese post-menopausal women with non-metastatic stage I–III ER+ breast cancer. The gene discussed is ESR1; the disease is breast cancer.