Fig. 4: Clinical vignette of a 52-year-old woman with HR + /HER2− metastatic breast cancer involving bone and gastric metastases.

The patient started first-line therapy with fulvestrant and abemaciclib. Baseline plasma analysis (prior to treatment start) showed a z-score <3, with detectable mutations in IDH2 (3.5% VAF) and TERT (0.3% VAF). After approximately 44 months of therapy, a second follow-up sample revealed a marked increase in IDH2 VAF (from 3.5% to 24.5%), clearance of the TERT mutation, and emergence of a new mutation in AKT1 (8.0% VAF). The z-score at follow-up remained below 3. Concurrent CT imaging demonstrated disease progression, with stable bone metastases and newly identified liver metastases. Created in Biorender.com.