AUTHOR=Ye Yanle , Zhang Zhishan , Zhao Hong , Zhao Bin 

TITLE=A system review of neoadjuvant immune checkpoint blockade for breast cancer

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1537926

DOI=10.3389/fimmu.2025.1537926

ISSN=1664-3224

ABSTRACT=BackgroundThe clinical application of immune checkpoint blockade (ICB)-based neoadjuvant therapy has been approved in breast cancer since 2021. However, no studies have evaluated its efficacy and safety in randomized and non-randomized settings. Additionally, there exists controversy about which specific subpopulation can benefit from this management strategy.MethodsWe searched MEDLINE and EMBASE databases for prospective clinical trials of ICB-based neoadjuvant therapy in breast cancer. Information regarding pathological complete response (pCR), event-free survival (EFS), overall survival (OS), and treatment-related adverse event (TRAE) were pooled to estimate the efficacy and safety. Hazard ratio, relative risk (RR) and their 95% confidence intervals (CIs) were calculated.ResultsAmong 22 eligible trials including 6134 women with resectable breast cancer, there were 11 randomized studies with 5574 patients. Pooled analysis on pCR (RR, 1.38; 95% CI, 1.20-1.58; P<0.001), EFS (hazard ratio, 0.67; 95% CI, 0.54-0.81; P<0.001), and OS (hazard ratio, 0.56; 95% CI, 0.35-0.91; P=0.01) revealed that ICB-based neoadjuvant therapy was associated with favorable outcomes over conventional treatment. Moreover, the benefits of EFS were independent of PD-L1 expression (Pinteraction=0.57) and pCR (Pinteraction=0.37) in neoadjuvant immunotherapy. However, combining ICB with conventional neoadjuvant treatment significantly increased the risk of high-grade TRAE (RR, 1.06; 95% CI, 1.01-1.12; P=0.03), serious TRAE (RR, 1.57; 95% CI, 1.26-1.94; P<0.001), treatment discontinuation due to TRAE (RR, 1.47; 95% CI, 1.14-1.90; P=0.003), and potentially fatal adverse event (RR, 2.25; 95% CI, 0.80-6.31; P=0.12).ConclusionThe combination of ICB with conventional neoadjuvant treatment is associated with favorable clinical outcomes and importantly, increased grade 3+ toxicities. Clinicians should meticulously monitor patients to minimize the risk of treatment discontinuation in individuals with potentially curable breast cancer.