Precision Medicine in Focus: Optimizing Biomarker-Driven Treatment Strategies in HR+/HER2– P13KCA-mutant Metastatic Breast Cancer - Episode 7
Beyond Single Biomarkers: How Emerging Data Might Transform Biomarker Testing
Panelists discuss how the SERENA-6 trial’s approach of serial liquid biopsy monitoring for ESR1 mutations raises important questions about the optimal timing and clinical benefit of molecularly guided therapy switches, with both experts preferring to see overall survival data before changing practice patterns.
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Current biomarker testing practices involve tissue biopsy confirmation of metastatic disease with repeat biomarker assessment (estrogen receptor (ER), progesterone receptor (PR), HER2) and comprehensive next-generation sequencing to identify actionable mutations, including PIK3CA. Timothy J. Pluard’s, MD, approach combines tissue and liquid biopsy testing, with tissue providing location-specific information and liquid biopsy offering broader mutation detection from all disease sites with faster turnaround times. This complementary strategy optimizes mutation detection while minimizing delays in treatment initiation, typically providing results within days for liquid biopsy vs a minimum of 3 weeks for tissue-based testing.
The discussion of SERENA-6 trial results, which demonstrated improved progression-free survival through ESR1 mutation monitoring and treatment switching, raised important questions about optimal biomarker utilization timing. Both experts expressed caution about implementing treatment changes based solely on liquid biopsy mutation detection without clinical progression, emphasizing the need for overall survival data before adopting such strategies. The concern is that ESR1 mutations may represent clonal evolution in limited disease sites while most of the disease remains controlled on current therapy.
The evolution toward more sophisticated biomarker strategies must balance early detection capabilities with clinical meaningfulness. Although liquid biopsy provides powerful tools for mutation monitoring, the translation to treatment decisions requires careful consideration of whether molecular changes truly represent clinically relevant disease progression requiring intervention. Future biomarker strategies will likely integrate multiple factors, including mutation burden, clonal evolution patterns, and clinical disease behavior to optimize treatment timing and selection, requiring additional clinical trial validation before widespread implementation in routine practice.
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