Navigating Treatment After Progression: Testing, ESR1 Mutations and Tolerable Options

Clinical Brief: Biomarker Testing Strategy in Second-Line Therapy

Main Discussion Topics:

• Strategic approach to biomarker testing when transitioning to second-line therapy
• Importance of liquid biopsy versus tissue biopsy for ESR1 mutation detection
• Role of PIK3CA and other pathway mutations in treatment selection
• Shared decision-making process for selecting between multiple treatment options
• Clinical assessment of endocrine sensitivity duration as a treatment predictor

Key Points for Physicians:

• Liquid biopsy preferred for ESR1 mutation detection due to subclonal nature (15%-20% better detection)
• PIK3CA mutations are clonal and detectable in the initial tissue biopsy
• Prior CDK4/6 inhibitor response duration greater than 12 months indicates endocrine sensitivity
• Multiple treatment options require individualized patient assessment
• Quality-of-life considerations balance with efficacy outcomes

The discussion emphasized that endocrine resistance is a complex phenomenon involving multiple pathways, not just ESR1 mutations, requiring comprehensive biomarker assessment for optimal treatment selection.