The histopathological and molecular features of breast carcinoma with tumour budding—a systematic review and meta-analysis

Purpose: Tumour budding (TB) is an adverse histological feature in many epithelial cancers. It is thought to represent epithelial–mesenchymal transition, a key step in the metastatic process. The significance of TB in breast carcinoma (BC) remains unclear. The aim of this study is to investigate the relationship between TB and other histological and molecular features of BC. Methods: A systematic search was performed to identify studies that compared features of BC based on the presence or absence of high-grade TB. Dichotomous variables were pooled as odds ratios (OR) using the Der Simonian–Laird method. Quality assessment of the included studies was performed using the Newcastle–Ottawa scale (NOS). Results: Seven studies with a total of 1040 patients (high-grade TB n = 519, 49.9%; low-grade/absent TB n = 521, 50.1%) were included. A moderate to high risk of bias was noted. The median NOS was 7 (range 6–8). High-grade TB was significantly associated with lymph node metastasis (OR 2.32, 95% c.i. 1.77 to 3.03, P ' 0.001) and lymphovascular invasion (OR 3.08, 95% c.i. 2.13 to 4.47, P ' 0.001). With regard to molecular subtypes, there was an increased likelihood of high-grade TB in oestrogen (OR 1.66, 95% c.i. 1.21 to 2.29, P = 0.002) and progesterone receptor-positive (OR 1.48, 95% c.i. 1.09 to 2.02, P = 0.01) tumours. In contrast, triple-negative breast cancer had a reduced incidence of high-grade TB (OR 0.46, 95% c.i. 0.30 to 0.72, P = 0.0006). Conclusion: High-grade TB is enriched in hormone receptor-positive BC and is associated with known adverse prognostic variables. TB may offer new insights into the metastatic process of BC.