Estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2−) breast cancer is a heterogeneous disease that includes a subpopulation of patients (including those with high-grade tumors and lymph node involvement) at high risk of recurrence who have poor long-term outcomes despite (neo)adjuvant chemotherapy and adjuvant endocrine therapy1. Here, ESR1 is linked to breast carcinoma.