2 Over 70% of these breast cancer diagnoses are estrogen receptor (ER) positive (ER+), with a 5–year survival rate of over 98% for localized tumors. However, once distant metastasis occurs, the 5–year survival rate decreases to <40%1. ,2 Bone, the most common site of metastasis in breast cancer patients, is involved in ~70% of all metastatic patients,1–4 and patients with bone metastasis have significantly reduced survival rates of <15%.1–6. Here, ESR1 is linked to bone metastasis.