Abstract
Abstract Background Several studies have demonstrated that the presence and the amount of tumor-infiltrating lymphocytes (TILs) are a potential biomarker of prognostic significance in some solid tumors. Data suggests that high levels of TILs are associated with favorable prognosis. However, whether TILs have any indication for prognosis in male breast cancer (MBC) patients remains unknown. In this study, we investigated the relationship between the expression and degree of CD8+ TILs, CD4+ TILs, and TILs and evaluated the prognostic value of these three factors in MBC. Methods We retrospectively identified 110 male breast cancer patients diagnosed between 2000 and 2013 at Salah Azaïz Cancer Institute. Stromal (str) CD8+ and CD4+ TILs were evaluated immunohistochemically. Two pathologists independently evaluated TILs levels using H&E stained slides following 2014 International TILs Working Group guidelines. Kaplan Meier and univariate and multivariate Cox regression analysis were applied to determine the association of CD8+ TILs, CD4+ TILs and TILs with clinicopathological features and overall survival (OS). Results The median for presence of str-CD8+TILs was 7% (0%-40%), str-CD4+TILs was 2% (0%-20%) and str-TILs was 10% (1%-40%). Only 12% of MBC patients had high str-CD8+TILs and 11% had high str-CD4+TILs. Fifty three percent had low str-TILs and 47% had moderate str-TILs. No lymphocyte predominant breast cancer was identified. Regarding intrinsic molecular subtypes, TNBC subtype and HER2 enriched tumors compared with Hormone receptor positive tumors had higher median levels of str-CD8+TILs, str-CD4+ TILs and str-TILs at diagnosis. However, increased level of str-CD8+ TILs, str-CD4+TILs and str-TILs weren't associated with improved OS in IHC subtypes (p=0.597, p=0.498 and p=0.456 respectively). On univariate analysis, higher levels of str-CD8+TILs, str-CD4+ TILs and str-TILs were associated with better OS (p=0.035, p=0.043 and p=0.040 respectively). Multivariate analysis identified str-CD8+ TILs and str-TILs as independent prognostic factors for OS ([HR= 0.851 (0.706-0.997), p=0.000] and [HR= 0.69 (0.43-0.96), p=0.045] respectively) but not str-CD4+ TILs (p=0.276). A high level of str-TILs was correlated with high str-CD8+ (p = 0.025). Conclusion The level of TILs in male breast cancer is low, suggesting prominent immune regulation/suppression in this disease. Str-CD8+ T cells and str-TILs represent potential prognostic markers in male breast cancer patients. Citation Format: Abdeljaoued S, Bettaieb I, Adouni O, Goucha A, Ghozzi R, Bouzaiene H, Hdiden M, Ben Hassouna J, Makhlouf R, El Benna F, Boussen H, Rahal K, Gamoudi A. Prognostic significance of CD8+ tumor-infiltrating lymphocytes (TILs), CD4+ TILs and TILs in male breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-15-01.
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