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Breast Cancer — SCE Medical Oncology MCQ

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HardBreast CancerBreast CancerSCE Medical Oncology

A 58-year-old woman with ER+/HER2- metastatic breast cancer and no prior systemic therapy for metastatic disease is found to have an activating ESR1 Y537S mutation on baseline ctDNA testing before any treatment. What is the clinical implication?

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Correct answer: D — This mutation confers constitutive ER activation and relative resistance to aromatase inhibitors; fulvestrant-based therapy may be preferred

While ESR1 mutations are most commonly acquired during AI therapy, they can occasionally be detected de novo. The Y537S mutation constitutively activates the oestrogen receptor ligand-independently, reducing AI efficacy. In this scenario, fulvestrant (a selective ER degrader) or novel oral SERDs may be preferred over aromatase inhibitors. CDK4/6 inhibitor combination remains indicated regardless of ESR1 status.

Reference: ESMO 2024 Metastatic Breast Cancer Living Guideline; Fribbens et al JCO 2016