Neoadjuvant anthracycline-free versus anthracycline-containing chemotherapy combined with dual HER2 blockade in HER2-positive breast cancer: a real-world comparative study

Anthracycline-free neoadjuvant chemotherapy combined with dual HER2 blockade represents an alternative to anthracycline-containing regimens in early-stage HER2-positive breast cancer; however, real-world evidence remains limited. We retrospectively analyzed 162 patients with stage I–III HER2-positive breast cancer treated with neoadjuvant trastuzumab and pertuzumab between 2022 and 2025. Patients received anthracycline-free (TCHP/TCH; n = 51) or anthracycline-containing (AC-THP/AC-TH; n = 111) chemotherapy. The primary endpoint was pathological complete response (pCR; ypT0/is ypN0). Secondary endpoints included treatment-related toxicity and cardiac safety. The overall pCR rate was 56.8%. pCR was achieved in 64.7% of patients in the TCHP/TCH group and 53.2% in the AC-THP/AC-TH group (p = 0.168). In multivariable analysis, age > 65 years was associated with a lower probability of pCR (OR 0.08; 95% CI, 0.01–0.57), while hormone receptor–negative status was associated with higher pCR rates (OR 2.21; 95% CI, 1.02–4.76). Grade 3–4 hematologic and gastrointestinal toxicities differed between regimens. Cardiac toxicity was rare and similar between groups. In a real-world setting, anthracycline-free neoadjuvant chemotherapy with dual HER2 blockade achieved pCR rates comparable to anthracycline-containing regimens with acceptable toxicity and preserved cardiac safety, suggesting that it may be a reasonable treatment option for selected patients.