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 (I2).

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.