Evaluation of the prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers.

Tian Tian,Ruohong Shui,Wentao Yang,Miao Ruan

doi:10.18632/oncotarget.10054

Abstract

Tumor-infiltrating lymphocytes (TILs) may be associated with clinical outcome in triple-negative breast cancers (TNBCs). However, lacking of standardized methodologies in TILs evaluation has hindered its application in clinical practice. To evaluate the prognostic role of TILs scored by methods recommended by International TILs Working Group 2014, we performed a retrospective study of TILs in 425 primary invasive TNBCs in a Chinese population with a median follow-up of 4 years. Intratumoral TILs (iTILs) and stromal TILs (sTILs) were scored respectively. The associations between TILs and disease-free survival (DFS), distant disease-free survival (DDFS) and overall survival (OS) were evaluated with COX models. ITILs were not associated with prognosis. Higher sTILs were associated with better prognosis; for every 10% increase in sTILs, a 5% reduction of risk of recurrence or death (P < 0.001), 5% reduction of risk of distant recurrence (P < 0.001), and 4% reduction of risk of death (P = 0.002) were observed. Multivariate analysis confirmed sTILs to be an independent prognostic marker. 3.5% of TNBCs had more than 50% lymphocytes (lymphocyte-predominant breast cancer, LPBC), and associations between LPBC status and prognosis were observed but did not reach statistical significance. TNBCs with more than 20% sTILs had a significantly better prognosis than the patients with no more than 20% sTILs. In conclusion, our study indicated that sTILs scored by methods recommended by International TILs Working Group 2014 were associated with the prognosis of TNBCs. STILs could be an independent prognostic biomarker in TNBCs, increasing sTILs predicting better prognosis.

Highlights

Triple-negative breast cancers (TNBCs) have been classified as a breast carcinoma subgroup which is negative for estrogen receptor (ER), progesterone receptor (PgR) and HER2 expression
Our study indicated that stromal Tumor-infiltrating lymphocytes (TILs) (sTILs) scored by methods recommended by International TILs Working Group 2014 were associated with the prognosis of triple-negative breast cancer (TNBC)
The mean patients’ age was 52 years. 61.9% of patients have no lymph node metastasis, 17.6% of patients have 1–3 lymph nodes metastasis and 14.8 % of patients have more than 3 lymph nodes involved. 413 (97.2%) TNBCs were diagnosed as invasive carcinoma of no special type and 2.8% were invasive breast carcinoma of special subtypes

Summary

Introduction

Triple-negative breast cancers (TNBCs) have been classified as a breast carcinoma subgroup which is negative for estrogen receptor (ER), progesterone receptor (PgR) and HER2 expression. Majority of TNBCs have a higher rate of distant recurrence and a poorer prognosis compared with other breast cancer subtypes [1,2,3]. Due to the absence of effective targeted therapies, new treatments for TNBCs should be developed currently. Immunologic therapy in breast cancers is upcoming, such as monoclonal antibodies blocking CTLA-4 and PD-1/PD-L1, which may be a new choice in TNBCs treatment in future [4]. Tumor-infiltrating lymphocytes (TILs) in the microenvironment of breast tumors have been proposed to reflect the efficacy to the immune therapy and to predict the prognosis of breast cancers [5,6]

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