🚨 SABCS25 Highlight | PHERGuide (PHERGain translational ctDNA analysis) A major step forward in reshaping early HER2+ breast cancer management. Key findings from this ctDNA-guided translational study: 🔬 Baseline insights: • ctDNA detected in 71% of patients; associated with stage & nodal status. • Baseline ctDNA did NOT predict pCR — reinforcing that tumor biology is dynamic, not static. ⚡ Early treatment dynamics: • ctDNA clearance by C3D1 strongly correlated with pCR (p=0.003). • Early molecular response outperformed baseline biomarkers. 🧬 Pre-surgery signal (most impactful): • 83% achieved ctDNA clearance pre-surgery. • 0% of patients with detectable ctDNA at surgery achieved pCR — a powerful negative predictive marker. • Pre-surgery ctDNA positivity associated with worse 3-year iDFS. 📈 Survival: • Both baseline ctDNA negativity and ctDNA clearance (early & late) predicted significantly better 3-year iDFS. 🌍 Why this matters now: This study strengthens a growing paradigm: ctDNA is emerging as an actionable tool to refine risk stratification, guide treatment escalation/de-escalation, and potentially reshape how we personalize therapy in early HER2+ disease—beyond imaging and pathology. 🔜 Clinical horizon: • Identify high-risk patients who may benefit from novel escalation (e.g., T-DXd strategies). • Support de-escalation trials for early molecular responders. • Integrate methylation-based ctDNA assays into upcoming HER2+ adjuvant/neo-adjuvant designs. An important translational contribution from PHERGain, pointing to the future of molecularly adaptive treatment in HER2+ eBC. @OncoAlert @weoncologists @ReduzziCarol