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

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.