ORIGINAL RESEARCH article
Front. Oncol.
Sec. Breast Cancer
Comprehensive Toxicity Profile of the 4AC-4THP Neoadjuvant Regimen in HER2-Positive Breast Cancer: A Multicenter Real-World Study in Vietnam
Anh Dinh Tran 1,2
TRINH Le Huy 1,2
Anh Tuan Pham 3
1. Hanoi Medical University, Hanoi, Vietnam
2. Hanoi Medical University Hospital, Hanoi, Vietnam
3. Vietnam National Cancer Hospital, Hanoi, Vietnam
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Abstract
Background: The 4AC-4THP regimen—comprising doxorubicin and cyclophosphamide followed by docetaxel, trastuzumab, and pertuzumab—has been widely adopted as neoadjuvant treatment for HER2-positive breast cancer. While efficacy data are well established, real-world safety data remain limited, particularly in Southeast Asian populations. Objective: To assess the comprehensive toxicity profile of the 4AC-4THP regimen, including both cardiac and non-cardiac adverse events, in Vietnamese patients with HER2-positive early-stage breast cancer. Methods: We conducted a retrospective multicenter study involving 52 women with stage II–III HER2-positive breast cancer treated with the 4AC-4THP neoadjuvant regimen at three oncology centers in Northern Vietnam between January 2020 and October 2024. Cardiotoxicity was assessed by serial echocardiography. Non-cardiac adverse events were graded according to CTCAE v5.0. Results: No patients developed symptomatic heart failure or experienced a decline in left ventricular ejection fraction (LVEF) below 50%. Subclinical LVEF reduction was observed in 78.8% of patients, with a mean decline of 8.05%, mostly during the anthracycline phase. Hematologic toxicities included neutropenia (42.3%, with 19.2% grade 3–4), anemia (46.2%), and thrombocytopenia (19.2%). Non-hematologic toxicities included fatigue/anorexia (76.9%), oral mucositis (67.3%), alopecia (100%), peripheral neuropathy (48.1%), and diarrhea (9.6%). All toxicities were manageable; no treatment-related deaths or discontinuations were reported. Conclusion: The 4AC-4THP neoadjuvant regimen in HER2-positive breast cancer showed acceptable tolerability in Vietnamese patients, especially among younger, low-comorbidity Asian populations. Subclinical cardiac dysfunction was common but mild and manageable. These findings provide further support for its use in neoadjuvant settings with appropriate monitoring strategies, especially in real-world clinical settings with variable access to monitoring resources.
Summary
Keywords
4AC-4THP, cardiotoxicity, HER2-positive breast cancer, Neoadjuvant chemotherapy, Real-world data, Vietnam
Received
03 August 2025
Accepted
20 February 2026
Copyright
© 2026 Tran, Le Huy and Pham. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Anh Dinh Tran
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