Precision Medicine in Focus: Optimizing Biomarker-Driven Treatment Strategies in HR+/HER2– P13KCA-mutant Metastatic Breast Cancer - Episode 6
Evolving Biomarker Testing Strategies for Earlier Detection in Metastatic Breast Cancer
Panelists discuss how biomarker testing strategies have evolved from second-line to first-line metastatic disease, driven by the availability of targeted agents for PIK3CA and ESR1 mutations, with both tissue and liquid biopsy approaches being used to ensure timely results for treatment decision-making.
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The evolution of targeted therapy availability has fundamentally shifted biomarker testing timing and strategy. Elsa Krill-Jackson, MD, described transitioning from testing at second relapse to up-front testing at first metastatic disease diagnosis. Previously, genomic testing was delayed because specific targeted therapies weren’t available for identified mutations. Now, with agents targeting ESR1 mutations (elacestrant) and PIK3CA mutations (multiple inhibitors), early identification enables optimal first-line treatment selection, particularly for patients with endocrine-resistant disease or prior CDK4/6 inhibitor exposure in the adjuvant setting.
The shifting landscape includes patients who have received adjuvant CDK4/6 inhibitors, potentially reducing the efficacy of first-line CDK4/6 inhibitor rechallenge in the metastatic setting. For these patients, early biomarker identification becomes even more critical to guide alternative approaches, such as triplet regimens for PIK3CA-mutated patients or ESR1-targeted therapy for appropriate mutations. The integration of liquid biopsy and tissue-based testing provides comprehensive mutation detection to inform treatment decisions from the outset of metastatic disease management.
Timothy J. Pluard, MD, emphasized that 25% to 30% of patients receiving first-line endocrine therapy plus CDK4/6 inhibitors experience rapid progression within the first few months, suggesting underlying genomic abnormalities that might benefit from alternative approaches. Understanding the genomic landscape of rapid progressors could inform decisions about moving PIK3CA inhibitors to first-line combination therapy. The evolution toward precision medicine requires earlier and more comprehensive biomarker testing, enabling clinicians to match patients with optimal targeted therapies from treatment initiation rather than after disease progression on standard approaches.
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