Advancements in Hormone Receptor-Positive Metastatic Breast Cancer - Episode 2

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

May 5, 2025
Virginia Kaklamani, MD, DSc

,
Megan Kruse, MD

Panelists discuss how to approach second-line therapy decisions for patients with metastatic breast cancer, emphasizing the importance of biomarker testing, including ESR1 mutations, and considering patient-specific factors.

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.