In this video, Aditya Bardia, MD, MPH, Massachusetts General Hospital, and Donald McDonnell, PhD, Duke University, explain that ESR1 mutations often arise in metastatic, hormone-receptor positive breast cancers after exposure to standard endocrine therapies, enabling the cancer to grow even without estrogen. They also emphasize that detecting ESR1 mutations (eg, via liquid biopsy) matters because the mutations can drive resistance to typical hormone treatments and may influence choice of newer therapies.