Prognostic Value of Tumor Budding for Early Breast Cancer

Abstract

Background: Tumor budding (TB) is a dynamic process associated with the epithelial-mesenchymal transition and a well-established prognostic biomarker for colorectal cancer. As part of the tumor microenvironment, tumor buds demonstrate increased cell motility and invasiveness. Current evidence demonstrates that high levels of TB correlate with disease progression and worst outcomes across different solid tumors. Our work aims to demonstrate the clinical applicability of TB analysis and its utility as a prognostic factor for patients with early breast cancer (EBC).

Methods: Retrospective, single-center, observational study, enrolling patients with EBC diagnosed in a Portuguese hospital between 2014 and 2015. TB classification was performed according to the International Tumor Budding Conference 2016 guidelines.

Results: A statistically significant relation was found between higher TB score and aggressive clinicopathological features (angiolymphatic/perineural invasion-p < 0.001; tumor size-p = 0.012; nuclear grading-p < 0.001; and Ki-67 index-p = 0.011), higher number of relapses (p < 0.001), and short disease-free survival (DFS) (p < 0.001).

Conclusion: We demonstrate that high TB correlates with shorter DFS and aggressive clinicopathological features used in daily practice to decide on the benefit of chemotherapy for EBC. TB represents a needed prognostic biomarker for EBC, comprising a new factor to be considered in the adjuvant decision-making process by identifying patients at a high risk of relapse and with higher benefit on treatment intensification. Clinical trials incorporating TB are needed to validate its prognostic impact.

Keywords: biomarker; early breast cancer; epithelial–mesenchymal transition; tumor budding.

Figure 1

ROC analysis demonstrated that a TB score of ≥5.5 buds was associated with a higher risk of relapse (AUC: 0.839; sensitivity:0.209; specificity:0.889). The red line represents the diagonal reference line. AUC: area under the curve. ROC: receiver-operating characteristics.