Neoadjuvant anthracycline-containing vs. anthracycline-free chemotherapy with dual HER2 blockade in HER2-Positive breast cancer: a Systematic Review and meta-analysis

Objectives Neoadjuvant chemotherapy with dual HER2 blockade is the standard of care for early-stage HER2-positive breast cancer. However, the role of anthracyclines remains controversial. This meta-analysis aimed to evaluate the efficacy and safety of neoadjuvant dual HER2 blockade combined with anthracycline-containing vs. anthracycline-free chemotherapy. Methods A literature search was conducted across PubMed, EMBASE, and the Cochrane Library. Eligible studies included patients with resectable stage I-III HER2-positive breast cancer receiving neoadjuvant dual HER2 blockade with either an anthracycline-containing (A-based) or anthracycline-free (non-A) chemotherapy regimen. Standard meta-analytic methods using a random-effects or fixed-effect model were applied according to heterogeneity (I 2 ). Results Seven articles met the inclusion criteria. The addition of anthracyclines to dual HER2 blockade therapy (DHBT) did not significantly improve the pCR rate (OR, 1.07; 95 % CI, 0.81–1.43; p=0.62), composite DFS/EFS/PFS (HR, 0.50; 95 % CI, 0.18–1.38; p=0.18), or overall survival (OS) (HR, 0.77; 95 % CI, 0.39–1.51; p=0.45). The incidence of cardiac adverse events did not differ significantly between the A-based and non-A groups (OR, 0.96; 95 % CI, 0.31–2.91; p=0.94). No significant difference was observed in the incidence of LVEF decline ≥10 % from baseline to <50 % between the A-based and non-A groups (OR, 1.47; 95 % CI, 0.79–2.77; p=0.23). Notably, the non-A group had a significantly higher incidence of grade ≥3 diarrhea (OR, 0.60, favoring the A-based group; 95 % CI, 0.38–0.95; p=0.03). Conclusions In resectable HER2-positive breast cancer, neoadjuvant DHBT without anthracyclines achieves pCR rates non-inferior to A-based regimens, with no early survival detriment observed. While short-term cardiotoxicity is unremarkable, grade ≥3 diarrhea occurs more frequently with non-A approaches.