Megan Kruse, MD

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

Clinical Brief: EMERALD Trial Insights for ESR1-Mutant Breast Cancer

Overview of EMERALD trial design and patient population

Co-primary end points and efficacy outcomes for ESR1-mutant tumors

Critical subset analyses identifying best responders (>12 months prior CDK4/6)

Median PFS outcomes: 8.6 months versus 3.8 months in optimal patients

Limited relevance of variant allele frequency (VAF) for treatment selection

Elacestrant approved specifically for ESR1-mutant metastatic breast cancer

Prior CDK4/6 duration greater than 12 months predicts better response (8.6 versus 1.9 months PFS)

Benefit maintained across visceral disease, multiple metastatic sites

PIK3CA co-mutations do not negate elacestrant benefit

VAF is not currently useful for treatment selection decision-making

The EMERALD trial established that patient selection based on endocrine sensitivity duration, rather than just mutation presence, optimizes treatment outcomes with elacestrant.

Videos

Panelists discuss how to communicate genomic testing results to patients and make shared treatment decisions, particularly when multiple targeted therapy options are available for patients with ESR1 and PIK3CA mutations.

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

Clinical Brief: Biomarker Testing Strategy in Second-Line Therapy

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

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.

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.

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

Clinical Brief: ESR1 Testing and Hormone Receptor-Positive Metastatic Breast Cancer

Introduction to ESR1 mutations in metastatic breast cancer, occurring in 40% to 50% of patients treated with anti-estrogen therapy

Mechanism of ESR1 mutations: allowing cancer cells to act as though estrogen is present even without it

Importance of testing for ESR1 mutations at different points during the treatment journey

Introduction of treatment options specifically targeting estrogen receptor, including elacestrant (Orserdu)

Differentiation between initial mutations versus those developing over time in response to therapy

ESR1 mutations develop as resistance mechanisms, particularly after aromatase inhibitor therapy

Testing timing is crucial - initial testing may miss mutations that develop later

ESR1 mutations occur in ligand-binding domain, causing constitutive receptor activation

Testing should consider both initial biopsy and liquid biopsy approaches at different stages

Patient-specific factors influence testing approach (de novo vs. recurrent disease)

The experts highlighted how ESR1 mutations represent acquired resistance rather than primary driver mutations, emphasizing the importance of serial testing throughout treatment. This understanding fundamentally changes how clinicians approach treatment sequencing in hormone receptor-positive breast cancer.

Panelists discuss how testing for specific changes in cancer cells, like ESR1 mutations, can help guide treatment choices for patients with hormone receptor-positive metastatic breast cancer.

Megan Kruse, MD

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

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

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

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