These remarkable results from the CALGB 9343 trial led to a change in the National Comprehensive Cancer Network (NCCN) Breast Cancer Guidelines in 2004, which suggested the omission of RT as a reasonable option for older women with low-risk breast cancer (early-stage, ER-positive, and node-negative) if they are treated with endocrine therapy [7]. This evidence concerns the gene ESR1 and breast cancer.