@article{cc871a66e23147c1b40bdc5977534eca,
title = "Prognostic value of tumor-infiltrating lymphocytes in patients with early-stage triple-negative breast cancers (TNBC) who did not receive adjuvant chemotherapy: Annals of Oncology",
abstract = "Background: Although stromal tumor-infiltrating lymphocytes (sTILs) have been considered an important prognostic factor in early-stage triple-negative breast cancer (TNBC), there have been limited data on their prognostic value in the absence of adjuvant chemotherapy. Patients and methods: A pooled analysis was carried out using four cohorts of TNBC patients not treated with chemotherapy. sTILs were evaluated in the most representative tumoral block of surgical specimens. Cox proportional hazards regression models were used for invasive disease-free survival (iDFS), distant disease-free survival (D-DFS), and overall survival (OS), fitting sTILs as a continuous variable adjusted for clinicopathologic factors. Results: We analyzed individual data of 476 patients from 4 centers diagnosed between 1989 and 2015. Their median age was 64 years. The median tumor size was 1.6 cm and 83% were node-negative. The median level of sTILs was 10% (Q1-Q3, 4%-30%). Higher grade was associated with higher sTILs (P < 10-3). During follow-up, 107 deaths, and 173 and 118 events for iDFS and D-DFS were observed, respectively. In the multivariable analysis, sTILs obtained an independent prognostic value for all end points (likelihood ratio χ2 = 7.14 for iDFS; P < 10-2; χ2 = 9.63 for D-DFS, P < 10-2; χ2 = 5.96 for OS, P = 0.015). Each 10% increment in sTILs corresponded to a hazard ratio of 0.90 [95% confidence interval (CI) 0.82 - 0.97] for iDFS, 0.86 (95% CI 0.77 - 0.95) for D-DFS, and 0.88 (95% CI 0.79 - 0.98) for OS, respectively. In patients with pathological stage I tumors with sTILs ≥30% (n = 74), 5-year iDFS was 91% (95% CI 84% to 96%), D-DFS was 97% (95% CI 93% to 100%), and OS was 98% (95% CI 95% to 100%). Conclusion: sTILs add important prognostic information in systemically untreated early-stage TNBC patients. Notably, sTILs can identify a subset of stage I TNBC patients with an excellent prognosis without adjuvant chemotherapy. {\textcopyright} 2019 The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.",
keywords = "adjuvant chemotherapy, prognosis, triple-negative breast cancer, tumor-infiltrating lymphocytes, doxifluridine, adult, age, aged, Article, cancer adjuvant therapy, cancer grading, cancer mortality, cancer patient, cancer prognosis, cancer radiotherapy, cancer size, cancer staging, cancer survival, cancer tissue, clinical feature, cohort analysis, confidence interval, controlled study, data analysis, diagnostic value, disease association, disease free survival, distant disease free survival, early cancer, female, follow up, hazard ratio, histopathology, human, human tissue, major clinical study, middle aged, multivariate analysis, overall survival, pooled analysis, priority journal, prognostic value, proportional hazards model, regression analysis, triple negative breast cancer, tumor associated leukocyte",
author = "J.H. Park and S.F. Jonas and G. Bataillon and C. Criscitiello and R. Salgado and S. Loi and G. Viale and H.J. Lee and M.V. Dieci and S.-B. Kim and A. Vincent-Salomon and G. Curigliano and F. Andr{\'e} and S. Michiels",
note = "Cited By :4 Export Date: 28 February 2020 CODEN: ANONE Correspondence Address: Michiels, S.; Service de Biostatistique et d'Epid{\'e}miologie, Gustave Roussy, B2M RDC, 114 rue Edouard Vaillant, France; email: stefan.michiels@gustaveroussy.fr Chemicals/CAS: doxifluridine, 3094-09-5 Funding details: Fondazione IRCCS Policlinico San Matteo, 7GZA Funding details: Universit{\`a} degli Studi di Padova Funding details: University of Ulsan, UOU Funding details: Research and Development Corporation of Newfoundland and Labrador, RDC Funding details: Konkuk University, KU Funding details: Istituto Oncologico Veneto, IOV Funding details: Agence Nationale de la Recherche, ANR, ANR-17-RHUS-0008 Funding details: Novartis Funding details: AstraZeneca France Funding details: Pfizer Funding details: Bristol-Myers Squibb, BMS Funding details: Eli Lilly and Company Funding details: Merck Funding text 1: 1Department of Medical Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul; 2Department of Hemato-Oncology, Konkuk Medical Center, University of Konkuk College of Medicine, Seoul, Korea; 3Department of Biostatistics and Epidemiology, Gustave Roussy; 4INSERM, Unit 1018, University Paris-Sud, University Paris-Saclay, Villejuif; 5Department of Pathology, Institut Curie, Universit{\'e} Paris Sciences Lettres, Paris, France; 6IEO, European Institute of Oncology, IRCCS, Milan, Italy; 7GZA, Antwerp, Belgium; 8Division of Clinical Medicine and Research, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; 9Department of Pathology, European Institute of Oncology, IRCCS, Milano, Italy; 10Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 11Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova; 12Veneto Institute of Oncology IOV – IRCCS, Padova, Italy; 13Inserm Unit 934, Paris, France; 14Department of Oncology and Hemato-Oncology, University of Milano, Milano, Italy; 15Department of Oncology, Gustave Roussy; 16INSERM, Unit 981, University Paris-Sud, University Paris-Saclay, Villejuif, France *Correspondence to: Dr. Stefan Michiels, Service de Biostatistique et d{\textquoteright}Epid{\'e}miologie, Gustave Roussy, B2M RDC, 114 rue Edouard Vaillant, 94805 Villejuif cedex, France. Tel: +33-1-42-11-41-44; E-mail: stefan.michiels@gustaveroussy.fr Funding text 2: This work is supported by Grant from the French National Research Agency (ANR) and the General Commission for Investment (CGI) (RHU MyPROBE, ANR-17-RHUS-0008). Funding text 3: CC: Consulting or advisory role in Pfizer, Roche, Lilly, Novartis. RS: none related to this work; travel, accommodations, expenses from Roche, Merck, AstraZeneca; consulting or advisory role: in Roche-Genentech, Bristol-Myers Squibb; research funding from Merck (Inst), Roche-Genentech (Inst), Puma (Inst). SL: consulting or advisory role in Seattle Genetics, Pfizer, Novartis, Merk, AstraZeneca, Roche-Genentech, Bristol-Myers Squibb; research funding from Merck (Inst), Roche-Genentech (Inst), Puma Biotechnology (Inst), Bristol-Myers Squibb (Inst), Pfizer (Inst), Eli Lilly (Inst). MVD: consulting or advisory role in Eli Lilly, Genomic Health, Celgene; travel, accommodations, and expenses from Pfizer, Celgene. S-BK: Consulting or advisory role in Novartis, Lilly, Daiichi Sankyo, Enzychem, Daehwa Pharm.CO.Ltd, ISU abxis; Research funding from Sanofi-Genzyme (Inst), Novartis (Inst), Dongkook (Inst). FA: consulting or advisory role in AstraZeneca, Novartis, Pfizer, Eli Lilly, Roche-Genentech, Daichi Sankyo; research funding from AstraZeneca (Inst), Novartis (Inst), Pfizer (Inst), Eli Lilly (Inst), Roche (Inst). SM: none related to this work; consulting or advisory role in Punctual statistical advice to IDDI (Belgium), Janssen Cilag (France); data and safety monitoring member: Hexal, J&J, Ipsen, Neovacs, Genticel, Mabxience, Steba, IQVIA, Roche, Sensorion, Biophytis, Servier. All remaining authors have declared no conflicts of interest. 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year = "2019",
doi = "10.1093/annonc/mdz395",
language = "English",
volume = "30",
pages = "1941--1949",
journal = "Ann. Oncol.",
issn = "1569-8041",
publisher = "NLM (Medline)",
number = "12",
}