Comparison of Anthracycline-Containing and Anthracycline-Free Neoadjuvant Regimens in HER2-Positive Breast Cancer

Background Concurrent administration of anti-HER2 therapies and chemotherapy has significantly improved response rates (43%–55%). However, the potential for cardiotoxicity when combining anti-HER2 agents with anthracyclines remains a concern. Consequently, anthracycline-free regimens are increasingly utilized, particularly for patients with cardiac history. This study aims to compare the efficacy and safety of anthracycline-containing chemotherapy versus anthracycline-free TCHP (Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab) regimens in the neoadjuvant treatment of HER2-positive early-stage breast cancer. Methods This multicenter retrospective study analyzed patients diagnosed with HER2-positive breast cancer between 2015 and 2025 who received neoadjuvant anti-HER2 therapy followed by surgery. We evaluated the association between treatment regimens and outcomes, specifically pathological complete response (pCR)—defined as the absence of residual invasive tumor in the breast and axillary nodes—and event-free survival (EFS). Results A total of 358 patients were included, with a mean age of 50 years. Most presented with T2 tumors (74%) and N1 disease (60.9%). The most common regimens were Adriamycin, Cyclophosphamide, Docetaxel, Pertuzumab, Trastuzumab (AC + DPT) (35.2%) and TCHP (30.7%), with a 95.5% treatment completion rate. Pathological complete response rates were statistically comparable between the AC + DPT and TCHP regimens (p = 0.360). Conversely, significantly lower pCR rates were observed with other regimens (OR 0.35, 95% CI 0.17–0.73; p = 0.005). Advanced lymph node involvement (N3) was strongly associated with worse event-free survival (HR 8.43, p = 0.038), while ER and PR status showed no significant impact. Regarding safety, febrile neutropenia was more frequent in the TCHP group (8.2%) compared to the AC + DPT group (1.6%). Notably, no Grade 3–4 cardiac toxicity was detected in either cohort (Table 1, 2; Fig. 1). Conclusions The TCHP regimen demonstrates efficacy comparable to anthracycline-containing regimens without increased cardiac toxicity, despite a higher incidence of hematological adverse events. Therefore, anthracycline-free regimens may be the preferred option for patients with cardiac comorbidities, while advanced lymph node involvement remains a critical poor prognostic factor.