Tumor Infiltrating Lymphocytes across Breast Cancer Subtypes: Current Issues for Biomarker Assessment

SIMPLE SUMMARY: Tumor-infiltrating lymphocytes (TILs) are immune cells that can be involved in the anti-tumor response and are presently viewed as a promising, inexpensive biomarker with prognostic and predictive potential. It has been demonstrated that patients with early triple-negative breast cancer and high TILs report higher responses to treatments with improved survival outcomes. Moreover, TIL expression may have a prognostic role in non-triple-negative subtypes and predict the response to immuno-oncology agents. However, the use of TILs as biomarkers in clinical practice is still limited by the lack of rigorous, prospective validation. This review summarizes the most important current issues and future challenges to assessing and validating TILs as predictive and prognostic biomarkers in patients with breast cancer. ABSTRACT: Tumor-infiltrating lymphocytes (TILs) represent a surrogate biomarker of anti-tumor, lymphocyte-mediated immunity. In early, triple-negative breast cancer, TILs have level 1B of evidence to predict clinical outcomes. TILs represent a promising biomarker to select patients who can experience a better prognosis with de-intensified cancer treatments and derive larger benefits from immune checkpoint inhibitors. However, the assessment and the validation of TILs as a biomarker require a prospective and rigorous demonstration of its clinical validity and utility, provided reproducible analytical performance. With pending data about the prospective validation of TILs’ clinical validity to modulate treatments in early breast cancer, this review summarizes the most important current issues and future challenges related to the implementation of TILs assessments across all breast cancer subtypes and their potential integration into clinical practice.