Triple-negative breast cancer survival prediction using artificial intelligence through integrated analysis of tertiary lymphoid structures and tumor budding

Abstract

Background: Triple-negative breast cancer (TNBC) is a highly heterogeneous and clinically aggressive disease. Accumulating evidence indicates that tertiary lymphoid structures (TLSs) and tumor budding (TB) are significantly correlated with the outcomes of patients who have TNBC, but no integrated TLS-TB profile has been established to predict their survival. The objective of this study was to investigate the relationship between the TLS/TB ratio and clinical outcomes of patients with TNBC using artificial intelligence (AI)-based analysis.

Methods: The infiltration levels of TLSs and TB were evaluated using hematoxylin and eosin staining, immunohistochemistry staining, and AI-based analysis. Various cellular subtypes within TLS were determined by multiplex immunofluorescence. Subsequently, the authors established a nomogram model, conducted calibration curve analyses, and performed decision curve analyses using R software.

Results: In both the training and validation cohorts, the antitumor/protumor model established by the authors demonstrated a positive correlation between the TLS/TB index and the overall survival (OS) and relapse-free survival (RFS) of patients with TNBC. Notably, patients who had a high percentage of CD8-positive T cells, CD45RO-positive T cells, or CD20-positive B cells within the TLSs experienced improved OS and RFS. Furthermore, the authors developed a comprehensive TLS-TB profile nomogram based on the TLS/TB index. This novel model outperformed the classical tumor-lymph node-metastasis staging system in predicting the OS and RFS of patients with TNBC.

Conclusions: A novel strategy for predicting the prognosis of patients with TNBC was established through integrated AI-based analysis and a machine-learning workflow. The TLS/TB index was identified as an independent prognostic factor for TNBC. This nomogram-based TLS-TB profile would help improve the accuracy of predicting the prognosis of patients who have TNBC.

Keywords: artificial intelligence; nomogram; tertiary lymphoid structures; triple‐negative breast cancer; tumor budding.