Duration of Tumor-infiltrating Lymphocytes Assessment with Significant Overall Survival Prognostic Value in Locally Advanced Breast Cancer

Abstract

Background Tumor microenvironment, represented by tumor-infiltrating lymphocytes, was dynamically evolving throughout the time. Thus, in the interpretation of TIL as a prognostic factor overall survival of breast cancer, it is important to note the duration of the TIL examination until neoadjuvant chemotherapy is performed.

Aim To determine whether the assessment of TIL at a certain duration still has value as a prognostic factor for the overall survival of breast cancer and its cut off point.

Methods This was a retrospective cohort study that included subjects with locally advanced breast cancer in Sanglah General Hospital, registered in Bali’s Cancer Registry. The study has been approved by the institutional review board of Udayana University, Denpasar, Bali. Data collected were age, breast cancer subtype, value of TIL, time of NAC start, and duration of survival. Missing data were obtained from electronic medical records. TIL is then grouped into groups with low TIL (negative and +1) and high TIL (+2 and +3). Data analysis were done with Statistical Package for the Social Sciences 25.0.

Results As many as 150 subjects with locally advanced breast cancer who survived and died in 2011-2020 were analyzed. The mean age of subjects in this study was 48.7 (SD 9.3) years with a median survival of 47 months. The mean duration of the TIL asessment to NAC was 46.3 days (SD 24.5). The duration cut off point of TIL assessment to NAC that is valuable as breast cancer’s overall prognostic value was 31 days (AUC 0.716, Sensitivity 64.1%, Specificity 35.5%). In subjects with TIL examined for less than 31 days, it was found that TIL could significantly prognosticated the overall survival of breast cancer (p = 0.005). High TIL was associated with better overall survival and low TIL is associated with poor overall survival.

Discussion Tumor immune microenvironment played an important role in tumor progression and supression.  High levels of TIL has been generally accepted as an indicator for a more robust anti-tumor immune response, thus yielding favorable outcome. Timing of TIL analysis was important to determine as microenvironment dynamically progressing. In this study, we proved that timing matters and only short-term duration of TIL assessment to NAC meaningful as a prognostic value for breast cancer’s overall survival.

Conclusion The duration of TIL to NAC assessment was important in determine the meaningful of TIL value in the prognostication overall survival of locally advanced breast cancer. The short-term TIL assessment duration (<31 days) predicted well, but not in the long term assessment duration. In the future, it is hoped that clinicians will be more critical in the interpretation of TIL, especially the duration of TIL assessment before NAC.