Supplemental Material for: Sustained clearance of circulating tumor DNA supports the de-escalation of first-line trastuzumab deruxtecan in a patient with metastatic HER2-positive breast cancer: case report

Despite pCR, she developed metastatic recurrence in the lungs approximately 25 months after initial diagnosis and 13 months after completion of adjuvant HER2-targeted therapy. First-line therapy with T-DXd plus pertuzumab (T-DXd+P) resulted in rapid ctDNA clearance after two cycles, sustained through eight cycles. She initially had a partial radiographic response and continued treatment with significant toxicity.

An informed decision was made to discontinue T-DXd+P after 8 cycles and to initiate a maintenance regimen of trastuzumab, palbociclib, and exemestane due to significant toxicities and supported by continued ctDNA negativity and radiographic response. </p><p dir="ltr">Conclusion: This case highlights the potential role of ctDNA-guided treatment individualization in metastatic breast cancer. Early ctDNA clearance may support consideration of treatment de-escalation to avoid cumulative or significant toxicity, although prospective validation is required.</p>