The Emerging Role of Tertiary Lymphoid Structures in Breast Cancer: A Narrative Review

Simple Summary This narrative review discusses the role of tertiary lymphoid structures (TLSs) in breast cancer. TLSs are ectopic lymphoid formations that can develop in response to inflammatory signals. They are present in about 60% of breast cancer cases and are particularly common in the triple-negative subtype. TLS presence is linked to better outcomes, and they could serve as prognostic and predictive markers for treatment response. Additionally, TLS-positive tumors may show improved outcomes regardless of other factors like PDL-1 expression or TILs. The emergence of TLS as a potential therapeutic avenue highlights the importance of standardized pathology methods for their detection in cancer research.Abstract This narrative review aims to clarify the role of tertiary lymphoid structures in breast cancer. We examine their development, composition, and prognostic value, and current ways of recognizing them. A comprehensive literature review was performed using the PubMed/Medline, Scopus, and EMBASE databases. A significant area of interest in breast cancer research involves targeting immune checkpoint molecules, particularly in the triple-negative subtype, where treatment options remain limited. However, existing biomarkers have limitations in accurately predicting treatment response. In this context, tertiary lymphoid structures (TLSs) emerge as a prognostic biomarker and also as a promising predictive marker for response. TLSs are ectopic lymphoid formations or neo-organogenesis that can develop after prolonged exposure to inflammatory signals mediated by chemokines and cytokines. Their presence is inversely correlated with estrogen receptor (ER) and/or progesterone receptor (PR) expression, but positively associated with a higher pathologic complete response rate and improved overall survival. In certain scenarios, TLS-positive tumors were associated with improved outcomes regardless of the presence of PDL-1 (programmed cell death ligand 1) expression or TILs (tumor-infiltrating lymphocytes).