Prognostic value of tumor-infiltrating lymphocyte subtypes in residual tumors of patients with triple-negative breast cancer after neoadjuvant chemotherapy

BACKGROUND: After neoadjuvant chemotherapy (NAC), non-pathological complete response of breast cancer patients can benefit from tailored adjuvant chemotherapy. However, it is difficult to select patients with poorer prognosis for additional adjuvant chemotherapy to maximize the benefits. Our study aimed to explore whether the subtypes of tumor-infiltrating lymphocytes (TILs) in residual tumors (RT) is related to the prognosis of triple-negative breast cancer (TNBC) after NAC. METHODS: Data from patients with primary TNBC consecutively diagnosed at the Breast Disease Center of Peking University First Hospital from 2008 to 2014 were retrieved, and the cases with RT in the breast after NAC were enrolled. TILs subtypes in RT were observed by double-staining immunohistochemistry, and counted with the median TILs value per square millimeter as the cut-off to define high versus low TILs density in each subtype. The relationships between the TIL density of each subgroup and the clinicopathological characteristics of the RT after NAC patients were analyzed by Fisher exact test. Disease-free survival (DFS) and overall survival (OS) were analyzed by the Kaplan-Meier method and log-rank statistics. RESULTS: A total of 37 eligible patients were included in this study, and the median follow-up period was 50 months (range 17–106 months). There was no significant correlation between the infiltrate density of CD4(+), CD8(+), CD20(+), and CD68(+) lymphocytes and clinic-pathological characteristics. Significantly better prognosis was observed in patients with high CD4(+)-TILs (DFS: P = 0.005, OS: P = 0.021) and high CD8(+)-TILs (DFS: P = 0.018) and low CD20(+)-TILs (OS: P = 0.042). Further analysis showed that patients with CD4(+)/CD20(+) ratio greater than 1 (DFS: P = 0.001, OS: P = 0.002) or CD8(+)/CD20(+) ratio greater than 1 (DFS: P = 0.009, OS: P = 0.022) had a better prognosis. CONCLUSIONS: Subtypes of TILs in RT is a potential predictive biomarker of survival in TNBC patients after NAC.