Clinical Scenario: Act on ESR1 Emergence or Wait

Neil Iyengar, MD, presents a case of a 52-year-old woman with bone-only, hormone receptor-positive, HER2-negative metastatic breast cancer on first-line ribociclib and letrozole who has stable imaging at 12 months but a new ESR1 Y537S mutation on ctDNA with mild bone pain. Carol Tweed, MD, says she would recommend switching therapy even without the bone pain, since a stable scan does not change the fact that progression is likely within months once this molecular signal appears. Rebecca Shatsky, MD, agrees, noting the Y537S variant's association with more aggressive disease and liver tropism, and cites SERENA-6 data showing 51% of patients who switched to camizestrant cleared ESR1-mutated ctDNA, a finding linked to improved survival. Both panelists say they would switch to camizestrant plus the patient's CDK4/6 inhibitor rather than wait for radiographic progression.