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

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

Main Discussion Topics:

• 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

Key Points for Physicians:

• 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.