Tumor-infiltrating lymphocytes and prognosis: A pooled individual patient analysis of early-stage triple-negative breast cancers

Sherene Loi, Damien Drubay, Sylvia Adams, Giancarlo Pruneri, Prudence A. Francis, Magali Lacroix-Triki, Heikki Joensuu, Maria Vittoria Dieci, Sunil Badve, Sandra Demaria, Robert Gray, Elisabetta Munzone, Jerome Lemonnier, Christos Sotiriou, Martine J. Piccart, Pirkko Liisa Kellokumpu-Lehtinen, Andrea Vingiani, Kathryn Gray, Fabrice Andre, Carsten DenkertRoberto Salgado, Stefan Michiels

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 x2, 48.9 iDFS; P < .001; x2, 55.8 D-DFS; P < .001; x2, 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.

Original languageEnglish (US)
Pages (from-to)559-569
Number of pages11
JournalJournal of Clinical Oncology
Volume37
Issue number7
DOIs
StatePublished - Jan 1 2019

Fingerprint

Triple Negative Breast Neoplasms
Tumor-Infiltrating Lymphocytes
Disease-Free Survival
Survival
Taxoids
Anthracyclines
Adjuvant Chemotherapy
Proportional Hazards Models
Drug Therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Tumor-infiltrating lymphocytes and prognosis : A pooled individual patient analysis of early-stage triple-negative breast cancers. / Loi, Sherene; Drubay, Damien; Adams, Sylvia; Pruneri, Giancarlo; Francis, Prudence A.; Lacroix-Triki, Magali; Joensuu, Heikki; Dieci, Maria Vittoria; Badve, Sunil; Demaria, Sandra; Gray, Robert; Munzone, Elisabetta; Lemonnier, Jerome; Sotiriou, Christos; Piccart, Martine J.; Kellokumpu-Lehtinen, Pirkko Liisa; Vingiani, Andrea; Gray, Kathryn; Andre, Fabrice; Denkert, Carsten; Salgado, Roberto; Michiels, Stefan.

In: Journal of Clinical Oncology, Vol. 37, No. 7, 01.01.2019, p. 559-569.

Research output: Contribution to journalArticle

Loi, S, Drubay, D, Adams, S, Pruneri, G, Francis, PA, Lacroix-Triki, M, Joensuu, H, Dieci, MV, Badve, S, Demaria, S, Gray, R, Munzone, E, Lemonnier, J, Sotiriou, C, Piccart, MJ, Kellokumpu-Lehtinen, PL, Vingiani, A, Gray, K, Andre, F, Denkert, C, Salgado, R & Michiels, S 2019, 'Tumor-infiltrating lymphocytes and prognosis: A pooled individual patient analysis of early-stage triple-negative breast cancers', Journal of Clinical Oncology, vol. 37, no. 7, pp. 559-569. https://doi.org/10.1200/JCO.18.01010
Loi, Sherene ; Drubay, Damien ; Adams, Sylvia ; Pruneri, Giancarlo ; Francis, Prudence A. ; Lacroix-Triki, Magali ; Joensuu, Heikki ; Dieci, Maria Vittoria ; Badve, Sunil ; Demaria, Sandra ; Gray, Robert ; Munzone, Elisabetta ; Lemonnier, Jerome ; Sotiriou, Christos ; Piccart, Martine J. ; Kellokumpu-Lehtinen, Pirkko Liisa ; Vingiani, Andrea ; Gray, Kathryn ; Andre, Fabrice ; Denkert, Carsten ; Salgado, Roberto ; Michiels, Stefan. / Tumor-infiltrating lymphocytes and prognosis : A pooled individual patient analysis of early-stage triple-negative breast cancers. In: Journal of Clinical Oncology. 2019 ; Vol. 37, No. 7. pp. 559-569.
@article{3c7067a6c3f840e7a816b45a85868244,
title = "Tumor-infiltrating lymphocytes and prognosis: A pooled individual patient analysis of early-stage triple-negative breast cancers",
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 x2, 48.9 iDFS; P < .001; x2, 55.8 D-DFS; P < .001; x2, 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.",
author = "Sherene Loi and Damien Drubay and Sylvia Adams and Giancarlo Pruneri and Francis, {Prudence A.} and Magali Lacroix-Triki and Heikki Joensuu and Dieci, {Maria Vittoria} and Sunil Badve and Sandra Demaria and Robert Gray and Elisabetta Munzone and Jerome Lemonnier and Christos Sotiriou and Piccart, {Martine J.} and Kellokumpu-Lehtinen, {Pirkko Liisa} and Andrea Vingiani and Kathryn Gray and Fabrice Andre and Carsten Denkert and Roberto Salgado and Stefan Michiels",
year = "2019",
month = "1",
day = "1",
doi = "10.1200/JCO.18.01010",
language = "English (US)",
volume = "37",
pages = "559--569",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "7",

}

TY - JOUR

T1 - Tumor-infiltrating lymphocytes and prognosis

T2 - A pooled individual patient analysis of early-stage triple-negative breast cancers

AU - Loi, Sherene

AU - Drubay, Damien

AU - Adams, Sylvia

AU - Pruneri, Giancarlo

AU - Francis, Prudence A.

AU - Lacroix-Triki, Magali

AU - Joensuu, Heikki

AU - Dieci, Maria Vittoria

AU - Badve, Sunil

AU - Demaria, Sandra

AU - Gray, Robert

AU - Munzone, Elisabetta

AU - Lemonnier, Jerome

AU - Sotiriou, Christos

AU - Piccart, Martine J.

AU - Kellokumpu-Lehtinen, Pirkko Liisa

AU - Vingiani, Andrea

AU - Gray, Kathryn

AU - Andre, Fabrice

AU - Denkert, Carsten

AU - Salgado, Roberto

AU - Michiels, Stefan

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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 x2, 48.9 iDFS; P < .001; x2, 55.8 D-DFS; P < .001; x2, 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.

AB - 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 x2, 48.9 iDFS; P < .001; x2, 55.8 D-DFS; P < .001; x2, 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.

UR - http://www.scopus.com/inward/record.url?scp=85062974425&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062974425&partnerID=8YFLogxK

U2 - 10.1200/JCO.18.01010

DO - 10.1200/JCO.18.01010

M3 - Article

C2 - 30650045

AN - SCOPUS:85062974425

VL - 37

SP - 559

EP - 569

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 7

ER -