Data from the SERENA-6 trial, presented at the 2025 American Society of Clinical Oncology Annual Meeting, have the potential to dramatically change advanced estrogen receptor–positive, HER2-negative breast cancer care, says William J Gradishar, MD, the Betsy Bramsen Professor of Breast Oncology at Northwestern University Feinberg School of Medicine in Chicago. The study showed benefit in switching therapies based on circulating tumor DNA evidence of ESR1 mutation, ahead of disease progression. “If we find that the magnitude of benefit seems to be as meaningful as it’s been reported to be, then I think what we will find in practice is more and more people will be doing next-generation sequencing testing, doing it earlier, and doing it more frequently to identify these mutations and act upon them,” Dr. Gradishar told Robert A. Figlin, MD, the interim director of Cedars-Sinai Cancer in Los Angeles and Steven Spielberg Family Chair in Hematology-Oncology. Dr. Gradishar also discussed key drugs in development, including selective estrogen receptor degraders, and questions about the sequencing of new treatments. “There may be diminishing returns, as we’ve seen with other drugs,” he noted.