Association between CD8+ Tumor Infiltrating Lymphocytes and the Clinical Outcome of Patients with Operable Breast Cancer Treated with Adjuvant Dose-Dense Chemotherapy—A 10 Year Follow-Up Report of a Hellenic Cooperative Oncology Group Observational Study

Abstract

Tumor-infiltrating lymphocytes (TILs) contribute to breast cancer (BC) prognosis. We investigated the prognostic impact of CD8+ TILs in patients with early breast cancer treated with adjuvant chemotherapy in a large observational clinical trial. Along with a 10 year follow-up, considering the efficacy and safety, we report the results of the translational part of our study. We examined the patients’ tumors for total (t), stromal (s), and intratumoral (i) CD8 lymphocyte density (counts/mm2) on tissue-microarray cores. The impact of CD8+ TILs counts on DFS and OS, and its correlation with breast cancer subtypes and standard clinicopathological parameters, were investigated, along with efficacy and safety data. Among the 928 eligible patients, 627 had available CD8+ data. Of which, 24.9% had a high expression of sCD8, iCD8, and total CD8, which were correlated with higher Ki67, TILs density, ER/PgR negativity, and higher histological grade. The 5year DFS and OS rates were 86.1% and 91.4%, respectively. Patients with high iCD8 and tCD8 had longer DFS and OS compared to those with low counts/mm2 (DFS: HR = 0.58, p = 0.011 and HR = 0.65, p = 0.034 and OS: HR = 0.63, p = 0.043 and HR = 0.58, p = 0.020, respectively). Upon adjustment for clinicopathological parameters, iCD8 and tCD8 retained their favorable prognostic significance for DFS and OS, whereas high sCD8 was only prognostic for DFS. Menopausal status, tumor size, and nodal status retained their prognostic significance in all examined multivariate models. CD8+ TILs, and especially their intratumoral subset, represent a potential favorable prognostic factor in early BC.

Expression of programmed death-ligand 1, IRF1 and CD8 T lymphocyte infiltration in a primary subset of breast cancer patients in Sudan

“…investigated the linkage of TILs to clinical outcomes in BC and found that the infiltration of CD8 was correlated to a higher Ki67 index. 23 , 24 Our present analysis found no evidence to support this correlation; this contradiction might be justified by the small number of samples with Ki67 data that were available for analysis.…”

Ten-year clinical outcome, toxicity and compliance of dose-dense sequential adjuvant administration of cyclophosphamide & epirubicin followed by docetaxel in patients with early breast cancer: A hellenic cooperative oncology group observational study (HE 10/10) with concurrent investigation of significance of tumor infiltrating lymphocytes

“…Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) were performed as previously described [ 30 , 31 ] on tissue microarrays (TMAs) consisting of 1.5 mm diameter tissue cores. Briefly, 3 μm of ΤΜΑ tissue sections were subjected to IHC staining with the corresponding antibodies in a Bond Max autostainer (Leica Microsystems, Wetzlar, Germany).…”

Unveiling the Immune Microenvironment’s Role in Breast Cancer: A Glimpse into Promising Frontiers

“…High densities of CD8+ TILs have consistently been associated with better clinical outcomes, including improved overall survival and disease-free survival. However, some studies have additionally emphasized the significance and prognostic relevance of stromal TILs [74]. Higher stromal TIL levels are linked to a better outcome in HER2+ BC patients [43].…”