Tumor infiltrating lymphocytes in breast cancer: A narrative review with focus on analytic validity, clinical validity, and clinical utility

Since Dr. Stephen Paget first proposed the "seed and soil" hypothesis in 1889, the tumor microenvironment has been recognized as a crucial component of tumor growth, progression, and metastasis. Tumor-infiltrating lymphocytes (TILs) are an important part of the tumor microenvironment, as well as an important prognostic and predictive biomarker for many cancers. This narrative review aims to summarize the current literature on the analytic validity, clinical validity, and clinical utility of TILs in breast cancer, including discussion of all major clinical subtypes. We summarize the current recommendations of the International Immuno-Oncology Biomarker Working Group on Breast Cancer for pathologist assessment and reporting of TILs, the state of the evidence justifying their usefulness as a biomarker in breast cancer, particularly for triple-negative and HER2+ breast cancer, as well as ongoing challenges and areas of future development, such as automated TIL scoring algorithms. Based on currently available evidence as well as ongoing clinical trials, we expect that TILs will increasingly become a cost-effective, easily available, and widely utilized biomarker in breast cancer, helping to guide treatment selection and optimization of therapy for many patients.