ESR1 and breast cancer: Breast cancer accounts for the highest number of cancer cases among women worldwide, and is the second leading cause of cancer death.[1, 2] Between two-thirds and three-quarters of breast tumors express the estrogen-receptor-alpha (ERα) protein.[3, 4] Patients with ER+ breast cancers usually receive adjuvant anti-estrogen therapy, typically tamoxifen—a selective ER modulator—or an aromatase inhibitor.