Tumor-infiltrating lymphocytes (TILs) have been a point of fascination since they were first described in the 1980s by Rosenberg et al in melanoma. In the modern era, TILs have been intensely studied as one of the important prognostic and predictive factors particularly for triple-negative and HER2-positive breast cancers. For oncologists, the degree of lymphocyte infiltration is predictive not only of a better local response to neoadjuvant treatment, but is also prognostic of long-term disease control. In 2014, the International TIL Working Group proposed a standardized method for evaluating TILs in breast cancer. TILs score was defined as the ratio of the area occupied by lymphocytes in the tumoral stroma to the whole area of tumoral stroma. The International Immuno-Oncology Biomarkers Working Group also used this method and published guidelines for evaluating TILs in other solid tumors. For pathologists, evaluating TILs in patients with breast cancer can be challenging because of tumor heterogeneity and interobserver variability. Breast core biopsies may be limited in sampling of the tumor and, in some cases, may not reflect the heterogeneity of the patient's breast cancer. Additionally, reporting TILs in 10th percentiles belies the subjectivity of a pathologist’s microscopic evaluation and may represent a level of granularity that is not reproducible between different pathologists. The National Comprehensive Cancer Network Breast Cancer Guidelines for 2021 do not comment on the use of TILs in the management of patients. In clinical practice, most pathologists will measure TILs as high or low using a cut off of 40 to 60. Assessment and use of TILs needs further refinement, and it remains to be seen if the guidelines can be widely adopted for reporting in a clinical setting by pathologists.
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