Anthracycline-free vs anthracycline-containing dual anti-HER2 neoadjuvant therapy: Real-world outcomes.

e12676 Background: The incremental value of anthracyclines with dual anti-HER2 neoadjuvant therapy (NAT) for early HER2+ breast cancer remains uncertain. We compared pCR, post-NAT escalation, and recurrence outcomes. Methods: Retrospective single-institution cohort of stage I–III HER2+ breast cancer treated with dual anti-HER2 NAT followed by surgery. Exposure: anthracycline-containing vs anthracycline-free TCHP. Primary endpoint: pCR. Secondary endpoints: post-NAT systemic therapy in non-pCR (trastuzumab emtansine [T-DM1] vs trastuzumab± pertuzumab), completion/discontinuation with reasons, and recurrence/RFS. Results: Of 112 evaluable patients, 74 (66.1%) received anthracycline-containing NAT and 38 (33.9%) TCHP. Overall pCR was 50.0% (56/112): 48.6% (36/74) vs 52.6% (20/38). pCR by subgroup (anthracycline vs TCHP): HR+ 43.2% vs 42.9%; HR− 56.7% vs 64.7%; cN0 52.4% vs 75.0%; cN+ 47.2% vs 42.3%; stage I–II 53.3% vs 61.9%; stage III 40.7% vs 41.2%. Among non-pCR (n = 56), post-NAT therapy was T-DM1 in 71.4% (40/56) and trastuzumab±pertuzumab in 26.8% (15/56) ; T-DM1 uptake was 78.9% (30/38) after anthracycline-containing NAT vs 55.6% (10/18) after TCHP. Early discontinuation occurred in 20.0% (8/40) for T-DM1 and 26.7% (4/15) for trastuzumab±pertuzumab; discontinuation due to toxicity was 87.5% and 50.0%, respectively. Cardiac-toxicity discontinuation was rare (1 per NAT arm). Recurrence occurred in 7.1% (4/56) with pCR vs 17.9% (10/56) without pCR; by NAT regimen 14.9% (11/74) vs 7.9% (3/38). Conclusions: Anthracycline-containing and anthracycline-free dual anti-HER2 NAT achieved comparable pCR in routine practice. Post-NAT escalation with T-DM1 was common; discontinuation was mainly toxicity-driven and cardiac discontinuation was rare. Larger cohorts with longer follow-up are needed to clarify comparative recurrence and safety outcomes.