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

Background

Trastuzumab deruxtecan (T-DXd) has demonstrated substantial efficacy in HER2-positive metastatic breast cancer; however, treatment-related toxicities may limit long-term tolerability. Circulating tumor DNA (ctDNA) is an emerging biomarker for minimal residual disease (MRD) and treatment response monitoring. Case Presentation: We report the case of a 57-year-old woman with high-grade, hormone receptor–positive, HER2-positive invasive ductal carcinoma who achieved a pathological complete response (pCR) following neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP). 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.