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Opinion|Videos|June 2, 2025

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

Author(s)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.

Episodes in this series

EP. 1 Understanding Cancer Changes and Testing: How Testing Guides Your Metastatic Breast Cancer Treatment

EP. 1 Understanding Cancer Changes and Testing: How Testing Guides Your Metastatic Breast Cancer Treatment

EP. 2 Navigating Treatment After Progression: Testing, ESR1 Mutations and Tolerable Options

EP. 2 Navigating Treatment After Progression: Testing, ESR1 Mutations and Tolerable Options

EP. 3 Exploring a Patient Case: Biomarker Testing After Progression and Discussing Treatment Choices With Your Care Team

EP. 3 Exploring a Patient Case: Biomarker Testing After Progression and Discussing Treatment Choices With Your Care Team

EP. 4 EMERALD Trial Results: What Prior CDK4/6i Duration Means for Treatment Success

EP. 4 EMERALD Trial Results: What Prior CDK4/6i Duration Means for Treatment Success

EP. 5 Managing Elacestrant Treatment: From Patient Selection to Supportive Care

EP. 5 Managing Elacestrant Treatment: From Patient Selection to Supportive Care

EP. 6 Real-World Experience: The Efficacy and Tolerability of Oral Elacestrant for Patients with ESR1 Mutations

EP. 6 Real-World Experience: The Efficacy and Tolerability of Oral Elacestrant for Patients with ESR1 Mutations

EP. 7 Patient Education, Shared Decision-Making, and Optimizing Care for ESR1-Mutated Breast Cancer

EP. 7 Patient Education, Shared Decision-Making, and Optimizing Care for ESR1-Mutated Breast Cancer

Video content above is prompted by the following:

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.

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