Tumor budding in breast carcinoma: A systematic review and meta-analysis

ABSTRACT Tumor budding is gaining importance as a prognostic factor in various carcinomas due to its association with epithelial–mesenchymal transition (EMT) and hence clinical outcome. Reporting tumor budding in breast cancer lacks homogeneity. We aim to systematically review the existing literature and conduct a meta-analysis to assess the prognostic implication of tumor budding in breast carcinoma. A systematic search was performed to identify studies that compared different prognostic variables between high- and low-grade tumor budding. Quality assessment was performed using a modified Newcastle Ottawa Scale. Dichotomous variables were pooled using the odds ratio using the Der–Simonian–Laird method. Meta-analysis was conducted to study the association between low/high-grade tumor budding and tumor grade, lymph node metastasis, lymphovascular invasion, ER, PR, HER2neu, KI67, and the molecular subtype triple-negative breast carcinoma. Thirteen studies with a total of 1763 patients were included. A moderate risk of bias was noted. The median bias scoring was 7 (6–9). High-grade tumor budding was significantly associated with lymph node metastasis (OR: 2.25, 95% CI: 1.52–3.34, P < 0.01) and lymphovascular invasion (OR: 3.14, 95% CI: 2.10–4.71, P < 0.01), and low-grade budding was significantly associated with triple-negative breast carcinoma (OR: 0.61, 95% CI: 0.39–0.95, P = 0.03) There was significant heterogeneity in the assessment and grading of tumor budding; thus, a checklist of items was identified that lacked standardization. Our meta-analysis concluded that tumor budding can act as an independent prognostic marker for breast cancer.