The prognostic value of the tumor-stroma ratio compared to tumor-infiltrating lymphocytes in triple-negative breast cancer: a review

Previous literature extensively explored biomarkers to personalize treatment for breast cancer patients. The clinical need is especially high in patients with triple-negative breast cancer (TNBC) due to its aggressive nature and limited treatment modalities. This review aims to evaluate the value of tumor-infiltrating lymphocytes (TILs) and tumor-stroma ratio (TSR) as prognostic biomarkers in TNBC patients and assess their clinical potential. A literature search was conducted in PubMed, Embase, Emcare, Web of Science, and Cochrane Library. Papers comparing survival outcomes of TNBC patients with low/high or negative/positive TSR and immune cells were included. The most frequently mentioned subgroups of TILs were selected and reported in this review. Data from 43 articles on TILs and eight articles on TSR were included. Among TNBC patients, high CD8 expression was generally associated with better survival. Notable, the poor survival outcomes were related to high intra-tumoral PD-L1 expression, whereas high stromal PD-L1 expression more often was correlated with favorable outcomes. For the TSR, a high amount of stroma in the primary tumor of TNBC patients was consistently associated with worse survival. This review highlights that a high number of CD8-positive T-cells is a promising prognostic factor for TNBC patients. PD-L1 expression analyzed for intra-tumoral and stromal expression separately reports strong but contrasting information. Finally, the TSR shows potential to be an important prognostic marker, especially for TNBC patients. Utilizing both biomarkers, either on itself or combined, could enhance clinical decision-making and personalization of treatment.