Overall, although margetuximab plus chemotherapy provided no OS benefit in the SOPHIA population compared with trastuzumab plus chemotherapy, margetuximab as post‐second‐line therapy offers an active alternative for patients with HER2‐positive ABC, and the findings of the SOPHIA study open the way to new lines of research aimed at developing Fc‐engineered anti‐HER2 antibodies for HER2‐positive breast cancer and other HER2‐positive carcinomas. This evidence concerns the gene ERBB2 and aneurysmal bone cyst.