In the Metastatic Breast Cancer Project (7), pathogenic ESR1 mutations were more common in hormone-positive metastatic versus primary tumors (13.2% vs 2.5% [5 of 38 vs 4 of 161], P = .01) and pretreated versus treatment-naïve tumors (11.1% vs 0% [4 of 36 vs 0 of 80], P = .008), consistent with previous reports (4,13). Here, ESR1 is linked to breast carcinoma.