How should clinicians navigate the growing number of treatment options for ESR1-mutated metastatic breast cancer?
Dr. Jason Mouabbi and Dr. Erika Hamilton discuss the evolving treatment landscape for hormone receptor-positive, HER2-negative metastatic breast cancer, with a focus on ESR1 mutations, molecular testing, PROTACs, oral SERDs, and treatment sequencing.
They explore when and how to test for ESR1 mutations, including the role of liquid biopsy and serial testing as resistance emerges. The conversation also examines the differences between a PROTAC and oral SERDs, the clinical data supporting vepdegestrant, and how emerging combination strategies could further reshape endocrine therapy.
Topics discussed:
• Why ESR1 mutations matter in HR-positive/HER2-negative metastatic breast cancer
• When to test and retest for ESR1 mutations
• Tissue NGS vs liquid biopsy for detecting ESR1 mutations
• ESR1 as both a resistance mechanism and a predictive biomarker
• Current treatment options for ESR1-mutated disease
• How PROTACs differ from oral SERDs
• VERITAC-2 and the clinical data supporting vepdegestrant
• Understanding VERITAC-2, EMERALD, and EMBER-3
• Tolerability, GI toxicity, fatigue, and QTc monitoring with vepdegestrant
• Selecting among endocrine monotherapy options
• Retesting ESR1 after progression on an oral SERD
• Sequencing a PROTAC after prior oral SERD therapy
• Imlunestrant plus abemaciclib and emerging combination strategies
• SERENA-6 and switching therapy at molecular progression
• Molecular progression vs radiologic progression
• The future role of PROTAC and CDK4/6 inhibitor combinations
• Why endocrine monotherapy still has an important role
• Preserving endocrine therapy before transitioning to antibody-drug conjugates
• Reconsidering endocrine therapy after treatment with an ADC
• The growing importance of genomic profiling and personalized treatment sequencing
▶️ Watch the full CHM Conversation for expert perspectives on ESR1 testing, endocrine resistance, treatment selection, and the evolving role of oral SERDs and PROTACs in metastatic breast cancer.
#JasonMouabbi #ErikaHamilton #CHMConversations #BreastCancer #MetastaticBreastCancer #ESR1 #HRPositiveBreastCancer #HER2Negative #Vepdegestrant #OralSERD #PROTAC #CommunityHealthMedia
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