Comprehensive toxicity profile of the 4AC-4THP neoadjuvant regimen in HER2-positive breast cancer: a multicenter real-world study in Vietnam

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.