Intratumoral CD8+ Cytotoxic Lymphocyte Is a Favorable Prognostic Marker in Node-Negative Breast Cancer

Background: The prognostic effect of tumor infiltrating CD8(+) cytotoxic lymphocytes (CTLs) in breast cancer is controversial. We analyzed the association between CD8(+) CTLs and survival of untreated node-negative breast cancer patients. Material and Methods: CD8(+) CTLs infiltrate was evaluated by immunostaining in a cohort of 332 node-negative breast cancer patients with a median follow-up of 152 months. The prognostic significance of CD8(+) CTLs for disease-free survival (DFS) and breast cancer-specific overall survival (OS) was evaluated with Kaplan-Meier survival analysis as well as univariate analysis and multivariate Cox analysis adjusted for age at diagnosis, pT stage, histological grade, estrogen receptor (ER) status, progesterone receptor (PR) status, Ki-67 expression and human epidermal growth factor receptor 2 (HER-2) status. Results: 285 (85.8%) patients showed strong CD8(+) CTLs infiltrate positive status. Univariate analysis showed that CD8(+) CTLs had statistically significant association with DFS (P = 0.004, hazard ratio [HR] = 0.454, 95% confidence interval [CI] = 0.265-0.777) and OS (P = 0.014, HR = 0.430, 95% CI = 0.220-0.840) in the entire cohort. The significance of CD8(+) CTLs was especially strong in ER negative, HER-2 negative and ER, PR, HER-2 triple-negative breast cancers. In Kaplan-Meier analysis, CD8(+) CTLs had significant effect on prognosis of patients (Log-rank test: P = 0.003 for DFS and P = 0.011 for OS), independent of established clinical factors for DFS (P = 0.002, HR = 0.418, 95% CI = 0.242-0.724) as well as for OS (P = 0.009, HR = 0.401, 95% CI = 0.202-0.797).