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

Abstract

Background

Tumor 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.

Methods

TILs 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.

Results

High 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.

Conclusions

High TILs tumors, especially LPBC seem worthy validating as a separate entity of favorable prognosis in breast cancer.

Journal

Journal ID (nlm-ta): Oncotarget

Journal ID (iso-abbrev): Oncotarget

Journal ID (publisher-id): Oncotarget

Journal ID (publisher-id): ImpactJ

Title: Oncotarget

Publisher: Impact Journals LLC

ISSN (Electronic): 1949-2553

Publication date Collection: 26 January 2016

Publication date (Electronic): 25 October 2015

Volume: 7

Issue: 4

Pages: 5074-5087

Affiliations

¹ Department of Pathology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece

² Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Thessaloniki, Greece

³ Health Data Specialists Ltd, Department of Biostatistics, Athens, Greece

⁴ Department of Medical Oncology, “Papageorgiou” Hospital, Thessaloniki, Greece

⁵ Department of Clinical Therapeutics, “Alexandra” Hospital, Athens, Greece

⁶ Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece

⁷ First Department of Medicine, “Laiko” General Hospital, Athens, Greece

⁸ Second Department of Medical Oncology, “Metropolitan” Hospital, Piraeus, Greece

⁹ Department of Pathology, “Papageorgiou” Hospital, Thessaloniki, Greece

¹⁰ Division of Oncology, Department of Medicine, University Hospital, Patras, Greece

¹¹ Second Department of Medical Oncology, “Agii Anargiri” Cancer Hospital, Athens, Greece

¹² Third Department of Medical Oncology, “Agii Anargiri” Cancer Hospital, Athens, Greece

¹³ Division of Oncology, Second Department of Internal Medicine, Attikon University Hospital, Athens, Greece

¹⁴ Department of Pathology, University Hospital of Patras, Rion, Greece

¹⁵ Oncology Unit, “Hippokration” Hospital, Athens, Greece

¹⁶ Second Department of Medical Oncology, Hygeia Hospital, Athens, Greece

¹⁷ Oncology Section, Second Department of Internal Medicine, “Hippokration” Hospital, Athens, Greece

Author notes

Correspondence to: Vassiliki Kotoula, vkotoula@ 123456auth.gr

Article

Publisher ID: 6231

DOI: 10.18632/oncotarget.6231

PMC ID: 4826267

PubMed ID: 26506242

Copyright statement: Copyright: © 2016 Kotoula et al.

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Categories

Subject: Clinical Research Paper