ctDNA Detected after Neoadjuvant Therapy for HER2-Positive Breast Cancer Is Associated with Inferior Outcomes and May
Po-Han Lin1,2, Li-Wei Tsai3, Chiao Lo3
1Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
Cancer Research Communications
|January 16, 2026
Summary
Residual ctDNA after neoadjuvant therapy in HER2+ early breast cancer predicts recurrence. Adjuvant T-DM1 may improve outcomes for ctDNA-positive patients, suggesting ctDNA status can guide treatment decisions.
Area of Science:
- Oncology
- Molecular Diagnostics
- Pharmacogenomics
Background:
- Circulating tumor DNA (ctDNA) is a known predictor of progression in metastatic breast cancer and recurrence in early breast cancer (EBC).
- The prognostic value of ctDNA persistence after neoadjuvant therapy (NAT) in HER2-positive (HER2+) EBC, particularly concerning the need for adjuvant T-DM1, remains under investigation.
Purpose of the Study:
- To investigate whether ctDNA positivity after NAT in HER2+ EBC patients who achieved pathologic complete response (pCR) indicates a poor prognosis.
- To determine if ctDNA status after NAT can guide the use of adjuvant T-DM1 therapy in HER2+ EBC.
- To assess the association between ctDNA dynamics and recurrence-free survival (RFS) in HER2+ EBC patients undergoing NAT.
Main Methods:
- Prospective study of 117 HER2+ EBC patients treated with NAT, analyzing ctDNA levels before and after therapy.
- Categorization of patients based on pCR status, ctDNA positivity/negativity post-NAT, and receipt of adjuvant T-DM1.
- Statistical analysis to evaluate the independent predictive value of ctDNA positivity for recurrence and its impact on RFS, comparing T-DM1 and non-T-DM1 groups.
Main Results:
- ctDNA positivity after NAT independently predicted recurrence in the non-T-DM1 group (HR, 5.505; P = 0.001).
- pCR patients with ctDNA positivity had significantly shorter RFS compared to ctDNA-negative patients (P = 0.008).
- Adjuvant T-DM1 improved ctDNA clearance rates (P = 0.035) and patients with ctDNA-positive/non-T-DM1 status had significantly shorter RFS (P = 0.029).
Conclusions:
- Persistent ctDNA after NAT in HER2+ EBC is associated with a poor prognosis and increased risk of recurrence.
- ctDNA positivity after NAT may serve as a crucial biomarker for identifying patients who could benefit from adjuvant T-DM1 therapy.
- Treatment with adjuvant T-DM1 can convert ctDNA-positive status to negative, improving RFS in HER2+ EBC patients.
