Among women with estrogen receptor (ER)–positive tumors, treatment with adjuvant endocrine therapy is generally recommended to reduce the risk of recurrence and improve survival.2 However, approximately one-half of patients with ER-positive disease do not benefit from endocrine therapy, and approximately 1 in 4 patients later develop distant metastasis and die of breast cancer.3,4. This evidence concerns the gene ESR1 and breast cancer.