Evolving ESR1 Mutation Testing Directions Complicate the Future of Metastatic Breast Cancer Management: With Pedram Razavi, MD, PhD; and Dara S. Ross, MD

In today’s episode, we welcomed Pedram Razavi, MD, PhD, and Dara S. Ross, MD. Dr Razavi is a breast medical oncologist and director of Liquid Biopsy & Genomics at Memorial Sloan Kettering Cancer Center in New York, New York. Dr Ross is an associate attending pathologist at Memorial Sloan Kettering Cancer Center.

In our exclusive interview, Drs Razavi and Ross discussed the evolution of ESR1 mutation–directed breast cancer management, emphasizing the role of comprehensive genomic testing at metastatic recurrence, including liquid biopsy and tissue sequencing. They highlighted that ESR1 mutations can develop in patients receiving aromatase inhibitors and that the detection of these mutations is crucial for treatment decisions. They also highlighted findings from the phase 3 SERENA-6 trial (NCT04964934), which tested switching to camizestrant upon the emergence of an ESR1 mutation during treatment with an aromatase inhibitor and a CDK4/6 inhibitor ahead of radiographic disease progression in patients with hormone receptor–positive, HER2-negative metastatic breast cancer. Despite concerns from the FDA's Oncologic Drugs Advisory Committee (ODAC) about SERENA-6’s design and overall survival outcomes, the experts praised the trial's innovative approach to personalizing breast cancer management based on biomarkers and noted ways that the ODAC decision may affect future clinical research in this field.