ESR1 mutations in breast cancer are acquired alterations, meaning they can be missed by a single test. The speaker advocates for serial testing, especially after disease progression, using blood-based ctDNA analysis. This dynamic monitoring approach is essential for identifying patients who become eligible for targeted therapies over time.
The ELEGANT trial enrolls all high-risk ER-positive patients, not just those with ESR1 mutations. The rationale is that unlike in metastatic disease, early breast cancer is fundamentally ER-driven. Elicestrin targets both wild-type and mutant ER, making the mutation status less critical for efficacy in this earlier setting.
The ELEGANT trial uses a "switch strategy," introducing elicestrin only after 2-5 years of standard therapy. This design pragmatically adapts to the evolving clinical landscape where CDK4/6 inhibitors are now standard initial treatment, ensuring the trial's relevance by testing the drug in a post-CDK4/6 inhibitor setting.