Serial ESR1 Mutation Testing in HR+/HER2– mBC: Insights From SERENA-6

SERENA-6 Study Results and Clinical Impact

The SERENA-6 study, presented at ASCO 2025’s plenary session, represents a paradigm shift in metastatic breast cancer treatment by switching therapy based on molecular progression rather than radiological progression. This approach involves monitoring for emergent ESR1 mutations before symptoms or imaging changes become apparent. The study investigates whether early therapeutic switching upon mutation detection can prevent eventual disease progression.

The study demonstrated impressive clinical outcomes with a progression-free survival improvement from baseline to approximately 16 months, achieving a hazard ratio of 0.4, representing a 60% improvement in outcomes. Patients who switched from aromatase inhibitors to elacestrant upon ESR1 mutation detection showed significantly better results than those continuing standard therapy. These results suggest substantial clinical benefit from proactive mutation monitoring.

Implementation challenges exist for this monitoring strategy in clinical practice. The study protocol required liquid biopsy testing every 2 months after 6 months of initial therapy, which demands significant healthcare infrastructure and resources. While academic medical centers may easily adopt this approach, community practices may face resource constraints. Despite these challenges, the compelling clinical data suggests this monitoring strategy will likely change standard practice patterns.