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J Clin Oncol. 2019 Mar 1;37(7):559-569. doi: 10.1200/JCO.18.01010. Epub 2019 Jan 16.

Tumor-Infiltrating Lymphocytes and Prognosis: A Pooled Individual Patient Analysis of Early-Stage Triple-Negative Breast Cancers.

Author information

1
1 Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC, Australia.
2
2 Gustave Roussy, Université Paris-Saclay, Villejuif, France.
3
3 Université Paris-Sud, Institut National de la Santé et de la Recherche Médicale, Villejuif, France.
4
4 New York University School of Medicine, New York, NY.
5
5 Fondazione Istituto di Ricovero e Cura a Carattere Scientifico-Isituto Nazionale dei Tumori, Universita degli Studi di Milano, Milan, Italy.
6
7 Helsinki University Central Hospital, Helsinki, Finland.
7
8 University of Padova, Padova, Italy.
8
9 Veneto Insitute of Oncology-IOV-IRCCS, Padua, Italy.
9
10 Indiana University, Indianapolis, IN.
10
11 Weill-Cornell Medicine, New York, NY.
11
12 Dana-Farber Cancer Institute, Boston, MA.
12
13 European institute of Oncology, Milan, Italy.
13
6 R&D UNICANCER, Paris, France.
14
14 Institut Jules Bordet, Universite Libre de Bruxelles, Brussels, Belgium.
15
15 Tampere University Hospital, Tampere, Finland.
16
16 University of Milan, Milan, Italy.
17
17 Charite Universite Hospital, Berlin, Germany.
18
18 GZA, Antwerp, Belgium.

Abstract

PURPOSE:

The aim of the current study was to conduct a pooled analysis of studies that have investigated the prognostic value of tumor-infiltrating lymphocytes (TILs) in early-stage triple negative breast cancer (TNBC).

METHODS:

Participating studies had evaluated the percentage infiltration of stromally located TILs (sTILs) that were quantified in the same manner in patient diagnostic samples of early-stage TNBC treated with anthracycline-based chemotherapy with or without taxanes. Cox proportional hazards regression models stratified by trial were used for invasive disease-free survival (iDFS; primary end point), distant disease-free survival (D-DFS), and overall survival (OS), fitting sTILs as a continuous variable adjusted for clinicopathologic factors.

RESULTS:

We collected individual data from 2,148 patients from nine studies. Average age was 50 years (range, 22 to 85 years), and 33% of patients were node negative. The average value of sTILs was 23% (standard deviation, 20%), and 77% of patients had 1% or more sTILs. sTILs were significantly lower with older age ( P = .001), larger tumor size ( P = .01), more nodal involvement ( P = .02), and lower histologic grade ( P = .001). A total of 736 iDFS and 548 D-DFS events and 533 deaths were observed. In the multivariable model, sTILs added significant independent prognostic information for all end points (likelihood ratio χ2, 48.9 iDFS; P < .001; χ2, 55.8 D-DFS; P < .001; χ2, 48.5 OS; P < .001). Each 10% increment in sTILs corresponded to an iDFS hazard ratio of 0.87 (95% CI, 0.83 to 0.91) for iDFS, 0.83 (95% CI, 0.79 to 0.88) for D-DFS, and 0.84 (95% CI, 0.79 to 0.89) for OS. In node-negative patients with sTILs ≥ 30%, 3-year iDFS was 92% (95% CI, 89% to 98%), D-DFS was 97% (95% CI, 95% to 99%), and OS was 99% (95% CI, 97% to 100%).

CONCLUSION:

This pooled data analysis confirms the strong prognostic role of sTILs in early-stage TNBC and excellent survival of patients with high sTILs after adjuvant chemotherapy and supports the integration of sTILs in a clinicopathologic prognostic model for patients with TNBC. This model can be found at www.tilsinbreastcancer.org .

PMID:
30650045
DOI:
10.1200/JCO.18.01010

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