Jing Zhang1, Mustapha Abubakar2, Pei Yuan1, Hela Koka2, Lei Guo1, Xin Li1, Xiaohong R Yang2, Jianming Ying1, Ning Lyu1. 1. Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021, China. 2. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda MD 20892, USA.
Abstract
PURPOSE: Tumor-infiltrating lymphocytes (TILs) have strong prognostic value in triple-negative and HER2-enriched breast cancer, but their prognostic role in luminal breast cancer (LBC) is less clear. Here, we assessed the overall TIL levels and CD8+ T-cells in relation to the prognosis of LBC patients from China. METHODS AND RESULTS: A total of 596 patients with LBC who were premenopausal and treated with adjuvant endocrine therapy were included. Among them, 160 cases were evaluated for CD8 by immunohistochemical (IHC) staining. Whole-section hematoxylin and eosin and IHC staining were visually assessed for stromal TILs (sTILs), stromal CD8+ T-cells (sCD8), and intratumoral CD8+ T-cells (iCD8). Multivariable analyses were used to test the associations between TILs and disease-free survival (DFS) and overall survival (OS) with the adjustment for clinicopathologic characteristics and treatment. High sTILs (≥10%) were associated with high histologic grade (P<0.001), luminal B/HER2- (P<0.001), luminal B/HER2+ subtype (P=0.002), and high Ki67 expression (≥25%; P=0.014). Similar associations were observed for sCD8 but not for iCD8. While sTILs and sCD8 were not associated with either DFS or OS, the presence of iCD8 (≥1%) was associated with better DFS in both univariate (HR=0.51, 95% CI 0.26-0.96, P=0.042) and multivariate (HR=0.48, 95% CI 0.25-0.92, P=0.027) analyses. Similar but less significant associations were found for iCD8 and OS (adjusted HR=0.35, 95% CI 0.11-1.10, P=0.073). CONCLUSIONS: Among Chinese premenopausal patients with LBC, iCD8 demonstrated suggestive associations with favorable outcome. In contrast, although sTILs and sCD8 were associated with more aggressive tumor features, they did not appear to be associated with clinical outcome. AJTR
PURPOSE: Tumor-infiltrating lymphocytes (TILs) have strong prognostic value in triple-negative and HER2-enriched breast cancer, but their prognostic role in luminal breast cancer (LBC) is less clear. Here, we assessed the overall TIL levels and CD8+ T-cells in relation to the prognosis of LBC patients from China. METHODS AND RESULTS: A total of 596 patients with LBC who were premenopausal and treated with adjuvant endocrine therapy were included. Among them, 160 cases were evaluated for CD8 by immunohistochemical (IHC) staining. Whole-section hematoxylin and eosin and IHC staining were visually assessed for stromal TILs (sTILs), stromal CD8+ T-cells (sCD8), and intratumoral CD8+ T-cells (iCD8). Multivariable analyses were used to test the associations between TILs and disease-free survival (DFS) and overall survival (OS) with the adjustment for clinicopathologic characteristics and treatment. High sTILs (≥10%) were associated with high histologic grade (P<0.001), luminal B/HER2- (P<0.001), luminal B/HER2+ subtype (P=0.002), and high Ki67 expression (≥25%; P=0.014). Similar associations were observed for sCD8 but not for iCD8. While sTILs and sCD8 were not associated with either DFS or OS, the presence of iCD8 (≥1%) was associated with better DFS in both univariate (HR=0.51, 95% CI 0.26-0.96, P=0.042) and multivariate (HR=0.48, 95% CI 0.25-0.92, P=0.027) analyses. Similar but less significant associations were found for iCD8 and OS (adjusted HR=0.35, 95% CI 0.11-1.10, P=0.073). CONCLUSIONS: Among Chinese premenopausal patients with LBC, iCD8 demonstrated suggestive associations with favorable outcome. In contrast, although sTILs and sCD8 were associated with more aggressive tumor features, they did not appear to be associated with clinical outcome. AJTR
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