Tumors with high-density tumor infiltrating lymphocytes constitute a favorable entity in breast cancer: a pooled analysis of four prospective adjuvant trials.

Vassiliki Kotoula,Helen Gogas,Angelos Koutras,Kyriakos Chatzopoulos,Flora Zagouri,Thomas Zaramboukas,George Fountzilas,Mattheos Bobos,Eleni Timotheadou,Pavlos Papakostas,George Pentheroudakis,Amanda Psyrri,Zoi Alexopoulou,Epaminontas Samantas,Ioannis Efstratiou,Eleni Galani,Sotiris Lakis,Dimitrios Pectasides,G Aravantinos ,Helen P Kourea ,P Kosmidis

doi:10.18632/oncotarget.6231

Abstract

BackgroundTumor infiltrating lymphocytes (TILs) are considered in the prognosis of breast cancer (BC) patients. Here, we investigated the prognostic/predictive effect of TILs in patients treated in the frame of four prospective trials with adjuvant anthracycline-based chemotherapy in the pre- and post-trastuzumab era.MethodsTILs density was histologically assessed as percentage of stromal area on whole routine sections of 2613 BC (1563 Luminal A/B; 477 Luminal HER2; 246 HER2-enriched; 327 triple negative [TNBC]) and were evaluated as high/low at three cut-offs (c/o; 50% [lymphocytic predominance, LP], 35% and 25%), in separate training and validation sets.ResultsHigh TILs were present in 3.5%, 6.5% and 11.5% of all tumors, using the 50%, 35% and 25% c/o, respectively. TILs status did not interact with BC subtypes or trastuzumab treatment. LPBC patient outcome was not affected by nodal status, while high TILs were favorable in TNBC with unfavorable nodal status. When adjusted for standard clinicopathological parameters and treatment, high TILs independently predicted for favorable outcome, e.g., disease-free survival with the 35% c/o in the entire cohort (HR = 0.44, 95% CI 0.28-0.69, p < 0.001) and in specific subtypes.ConclusionsHigh TILs tumors, especially LPBC seem worthy validating as a separate entity of favorable prognosis in breast cancer.

Highlights

Tumor infiltrating lymphocytes (TILs) within the tumor stroma or within tumor nests reflect the host immune response against the tumor, described as cancer “immunoediting” [1]
High TILs tumors, especially lymphocyte-predominant breast cancer (LPBC) seem worthy validating as a separate entity of favorable prognosis in breast cancer
In the present pooled analysis, we investigated the effect of TILs on the outcome of more than 2500 patients with operable breast cancer who were treated in the setting of prospective trials conducted by the Hellenic Cooperative Oncology Group (HeCOG)

Summary

Introduction

Tumor infiltrating lymphocytes (TILs) within the tumor stroma or within tumor nests reflect the host immune response against the tumor, described as cancer “immunoediting” [1]. Similar TILs effects were noticed in the neoadjuvant setting [4, 6, 11, 12] and in the adjuvant setting as well [5, 7, 8, 11], while the presence of TILs in residual disease after initial chemotherapy may indicate favorable outcome [13]. Tumor infiltrating lymphocytes (TILs) are considered in the prognosis of breast cancer (BC) patients. We investigated the prognostic/ predictive effect of TILs in patients treated in the frame of four prospective trials with adjuvant anthracycline-based chemotherapy in the pre- and post-trastuzumab era

Methods

Results

Conclusion