27P - 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

Background

Tumor-infiltrating lymphocytes (TILs) and their subsets contribute to breast cancer prognosis. We investigated the prognostic impact of CD8+ TILs in patients with early intermediate/high-risk breast cancer treated with adjuvant anthracycline-based chemotherapy.

Methods

All patients received dose-dense sequential chemotherapy with E-T-CMF regimen. We examined their tumors for total, stromal (s) and intratumoral (i) CD8 lymphocyte density (counts/mm2) on tissue-microarray cores by immunohistochemistry. Morphological sTIL density was also evaluated. Impact of CD8+ TILs counts on DFS and OS and its correlation with breast cancer (IHC4) subtypes and standard clinicopathological parameters were investigated along with efficacy and safety data.

Results

990 patients were enrolled from which 627 had available CD8 data. The median number of sCD8 and iCD8 counts/mm² was 113.7 and 3.7, respectively. 156 (24.9%) had high expression of sCD8, iCD8 and total CD8 and were strongly correlated with higher Ki67, TILs density, ER/PgR negativity and higher histological grade. At a median follow-up of 132.5 months, the median DFS and OS have not been reached yet. 5-year DFS and OS rates were 86.1% and 91.4% respectively. Patients with high intratumoral and total CD8 had longer DFS and OS as 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 total CD8 retained their favorable prognostic significance for DFS and OS, whereas high sCD8 was significantly associated with prolonged DFS. Menopausal status, tumor size and nodal status retained their prognostic significance in all examined multivariate models. TILs density and CD8 status did not interact with BC subtypes.

Conclusions

CD8+ TILs and especially their intratumoral subset, represent a potential favorable prognostic factor and impact survival rates in early breast cancer. Further research is needed to establish their role in breast cancer prognosis.

Clinical trial identification

ACTRN12615000161527.

Legal entity responsible for the study

Hellenic Cooperative Oncology Group.

Funding

Hellenic Cooperative Oncology Group.

Disclosure

All authors have declared no conflicts of interest.