Prognostic Value of Tumor-Infiltrating Lymphocytes in Breast Cancer Patients Treated With Radiotherapy: A Systematic Review of Literature

High tumor-infiltrating lymphocytes (TILs) levels in triple-negative and HER2-positive breast cancer are associated with better survival outcomes, highlighting its potential as prognostic biomarkers. Radiotherapy can also trigger immune cell infiltration. This systematic review evaluates the prognostic value of TILs in radiotherapy-treated breast cancer patients. A literature search (in PubMed, Embase and Web of Science) was performed up to April 5, 2024 (PROSPERO registration CRD42024401741). Two independent reviewers screened articles according to predefined criteria, resolving discrepancies through consensus. The collected outcomes were prognostic value of TILs for ipsilateral breast tumor recurrence (IBTR), any recurrence, distant metastasis (DM), overall survival (OS) and disease-free survival (DFS). Of 10,927 records, 11 studies (3899 patients) were included. Patients underwent lumpectomy or mastectomy, with or without postoperative radiotherapy. Three studies examined neoadjuvant partial breast irradiation. The stroma threshold for high vs. low TILs ranged from 5 to 50%, with most patients (73%) having low TILs. Low TILs patients significantly benefited from radiotherapy in reducing IBTR and any recurrence. In luminal B, triple-negative and HER2-positive subtypes, high TILs were associated with better outcomes in DM, OS and DFS. For radiotherapy-treated luminal A breast cancer, low TILs were associated with improved OS. For DCIS patients, low TILs correlated with reduced IBTR. TILs could be a prognostic biomarker for radiotherapy-treated breast cancer patients. However, study heterogeneity complicates comparisons. To refine personalized treatment, further prospective studies are necessary to investigate TILs levels and the impact of neoadjuvant radiotherapy on oncological outcomes across different breast cancer subtypes.