C23Stromal peritumoral and intratumoral infiltrating lymphocytes: how immunity influences prognosis in triple negative breast cancer

Background: Triple negative breast cancer (TNBC) is an aggressive subgroup of breast cancer (BC) with poor clinical outcome. The lack of target therapies switches attention on the role of immune interaction between host and tumor. Tumor-infiltrating lymphocytes (TILs) is a biomarker of immunogenity that in TNBC can correlate with DFS and OS. The aim of our study was to evaluate the prognostic role of TILs and its association with clinicopathological parameters in TNBC. Materials and methods: Nine-three consecutive patients with primary diagnosis of TNBC referred to our institution between January 2009 and December 2015 were enrolled. We collected their clinicopathological data. In each tumor sample the pathologist evaluated stromal intratumoral TIL percentage (area of stroma occupied by infiltrating lympochytes) and stromal peritumoral TIL percentage (percentage of stroma lymphocytes encountered in entire circumferential invasive tumor front). Lymphocytes predominant breast cancer (LPBC) were the ones with TILs higher than 60%. TILs were correlated with clinicopathological data, OS (time between diagnosis and death or last follow up) and DFS (time between diagnosis and relapse either as local recurrence or distant metastasis). All data were analyzed by Chi square test. Kaplan-Meier curves for OS and DFS were applied. Univariate and multivariate Cox proportional hazard models were conducted to correlate between TIL, OS and DFS. Level of significance p value was set at 0.05. Results: We found a significant association between stromal intratumoral TIL and stromal peritumoral TIL (p = 0.0082). A significant difference was also seen in LPBC subgroup (p = 0.0001 95% CI 3,4761-33,5857). There was no significant correlation between both intratumoral and peritumoral TIL and the clinicopathological data examined. Peritumoral TIL was significantly associated with OS (p = 0.0119 95% CI 1,7109-75,541) and DFS (p = 0.0113 95%CI 1,5723-34,8046), the latter regardless of TIL percentage of expression. Intratumoral TIL did not demonstrate significant correlation with DFS, unless a TIL percentage =1% (p = 0,029 95%CI 1,1266-10,3296), nor with OS. At the multivariate analysis TIL did not show a significant correlation with OS and DFS. Conclusions: Peritumoral TIL correlates with DFS and OS in TNBC. This is an intriguing data not enough considered in literature yet which suggest that the location of TIL may help to stratify prognostic BC subgroups to guide future therapeutic decisions.