The relationship between tumor budding and survival of patients with breast cancer: A meta-analysis

Tumor budding has been proposed as a potential prognostic marker in various cancers, but its association with survival outcomes in breast cancer (BC) remains unclear. This meta-analysis aimed to clarify the relationship between tumor budding and survival outcomes in patients with BC. A comprehensive literature search was conducted in PubMed, EMBASE, and Web of Science. Cohort studies examining the association between tumor budding and overall survival (OS) and progression-free survival (PFS) in BC patients were included. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled using a random-effects model to account for potential heterogeneity. Eleven cohort studies, including 2,828 patients, met the inclusion criteria. High tumor budding was significantly associated with poorer OS (HR = 1.89, 95% CI = 1.37-2.60, P < 0.001) and PFS (HR = 1.89, 95% CI = 1.32-2.71, P < 0.001). Subgroup analyses revealed a stronger association in studies where high tumor budding was defined as ≥ 10 buds / high-power field (HPF) compared to those with lower cutoffs. Sensitivity analyses confirmed the robustness of the findings. This meta-analysis demonstrates that high tumor budding is associated with significantly worse OS and PFS in BC patients, underscoring its prognostic significance. These findings suggest tumor budding could be a valuable marker in clinical assessments, and further research is needed to standardize its evaluation criteria in BC.