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
N1 - Publisher Copyright:
© 2019 by American Society of Clinical Oncology.
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
U2 - 10.1200/JCO.18.01010
DO - 10.1200/JCO.18.01010
M3 - Article
C2 - 30650045
AN - SCOPUS:85062974425
SN - 0732-183X
VL - 37
SP - 559
EP - 569
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 7
ER -