Editor’s Note: This interview was recorded shortly before the 2025 American Society of Clinical Oncology Annual Meeting. Big questions associated with ESR1 mutations in patients with hormone receptor–positive breast cancer may soon have answers. New data are “going to take the whole breast oncology field from one place and put it in a different place. It’s going to be an inflection point in our history of treating breast cancer,” says Jason Aboudi Mouabbi, MD, assistant professor in the Department of Breast Medical at the University of Texas MD Anderson Cancer Center in Houston. Speaking with Robert A. Figlin, MD, the interim director of Cedars-Sinai Cancer in Los Angeles and Steven Spielberg Family Chair in Hematology-Oncology, Dr. Mouabbi outlined current challenges in identifying and responding to the development of ESR1 mutations. Dr. Figlin and Dr. Mouabbi also discussed how eagerly anticipated findings may transform practice and important aspects of mutational testing to consider. Dr. Mouabbi reported consulting fees from GE Healthcare, Genentech, AstraZeneca, Gilead, Novartis, Fresenius Kabi, BostonGene, and Cardinal Health. Dr. Figlin reported various financial relationships.