Tumor-Infiltrating Lymphocytes (TILs) in Early Breast Cancer Patients: High CD3(+), CD8(+), and Immunoscore Are Associated with a Pathological Complete Response

Simple Summary: In 2021, the World Health Organization announced that breast cancer had overtaken lung cancer to become the most common cancer globally, accounting for 12% of all new cancer cases, with younger women resident in low-income countries having the lowest 5-year survival rates. The main aim of the current study was to evaluate the prognostic utility of an innovative, objective, computer-assisted, digital imaging procedure known as the Immunoscore for clinical research (ISCR) as a strategy to reveal the efficiency of the anti-tumor cellular immune landscape of the tumor microenvironment (TME) in biopsies taken from women diagnosed with early breast cancer prior to administration of neoadjuvant chemotherapy followed by surgical resection. Our results demonstrated the ability of the ISCR to enumerate tumor-infiltrating lymphocytes in the TME and, in particular, to illustrate the spatial arrangement of these cells, which, importantly, correlated with clinical outcome, measured as the pathological complete response. Background: Tumor-infiltrating lymphocytes are associated with a better prognosis in early triple-negative breast cancer (TNBC). These cells can be enumerated in situ by the "Immunoscore Clinical Research" (ISCR). The original Immunoscore (R) is a prognostic tool that categorizes the densities of CD3(+) and CD8(+) cells in both the invasive margin (IM) and center of the tumor (CT) in localized colon cancer, yielding a five-tiered classification (0-4). We evaluated the prognostic potential of ISCR and pathological complete response (pCR) following neoadjuvant chemotherapy (NACT). Methods: The cohort included 53 TNBC, 32 luminal BC, and 18 HER2-positive BC patients undergoing NACT. Pre-treatment tumor biopsies were immune-stained for CD3(+) and CD8(+) T-cell markers. Quantitative analysis of these cells in different tumor locations was performed using computer-assisted image analysis. Results: The pCR rate was 44%. Univariate analysis showed that primary tumor size, estrogen-receptor negative, progesterone-receptor negative, luminal vs. HER2-positive vs. TNBC, high Ki-67, high densities (cells/mm(2)) of CD3 CT, CD8(+) CT, CD3(+) IM, and CD8(+) IM cells were associated with a high pCR. ISCR was associated with pCR following NACT. A multivariate model consisting of ISCR and the significant variables from the univariate analysis showed a significant trend for ISCR; however, the low sample size did not provide enough power for the model to be included in this study. Conclusions: These results revealed a significant prognostic role for the spatial distributions of the CD3(+), and CD8(+) lymphocytes, as well as the ISCR in relation to pCR following NACT.