Clinical validity of tumor-infiltrating lymphocytes analysis in patients with triple-negative breast cancer

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Abstract

Background: Although tumor-infiltrating lymphocytes (TILs) have been associated with a favorable prognosis in triplenegative breast cancer (TNBC) patients, this marker is not currently considered robust enough for entering the clinical practice. In the present study, we assessed the clinical validity of the guidelines recently issued by the International TIL Working Group in a large retrospective series of well-annotated TNBC patients. Patients and methods: TILs were evaluated in all the full-face H & E sections from 897 consecutive TNBC (i.e. tumors with >1% of ER and PgR immunoreactivity and absence of HER2 overexpression or amplification) patients diagnosed and treated at the European Institute of Oncology between 1995 and 2010 (median follow-up 8.2 years, range 6 months to 18 years). All mononuclear cells were evaluated in the stromal area within the borders of the invasive tumor, reported as a percentage value and treated as a continuous variable in survival analysis. Results: The median percentage of TILs was 20%, and 21.9% of the cases had =50% (lymphocyte predominant breast cancer, LPBC) TILs. At univariable survival analysis, TILs were a significant predictor of better disease-free survival (DFS), distant disease-free survival (DDFS) and overall survival (OS) (P <0.0001). Multivariable analysis confirmed that each 10% increase in TILs strongly predicted better survival, independent of patients' age, lymph node status, tumor size, histological grade, peritumoral vascular invasion and Ki-67 labeling index. Patients with LPBC had a 10-year survival rate of 71%, 84% and 96% for DFS, DDFS and OS, respectively. Stratified analysis revealed a positive correlation between TILs and OS across all the subgroups analyzed. Conclusion: Our data support the analytical validity of the recently issued TILs evaluation guidelines in the clinical practice.

Original languageEnglish
Article numbermdv571
Pages (from-to)249-256
Number of pages8
JournalAnnals of Oncology
Volume27
Issue number2
DOIs
Publication statusPublished - Feb 1 2016

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Triple Negative Breast Neoplasms
Tumor-Infiltrating Lymphocytes
Breast Neoplasms
Disease-Free Survival
Survival
Survival Analysis
Guidelines
Lymphocytes
Neoplasms
Blood Vessels
Survival Rate
Lymph Nodes

Keywords

  • Breast
  • Cancer
  • Chemotherapy
  • Survival
  • Triple negative
  • Tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

@article{7129596d206a49c288348cf063d4c56f,
title = "Clinical validity of tumor-infiltrating lymphocytes analysis in patients with triple-negative breast cancer",
abstract = "Background: Although tumor-infiltrating lymphocytes (TILs) have been associated with a favorable prognosis in triplenegative breast cancer (TNBC) patients, this marker is not currently considered robust enough for entering the clinical practice. In the present study, we assessed the clinical validity of the guidelines recently issued by the International TIL Working Group in a large retrospective series of well-annotated TNBC patients. Patients and methods: TILs were evaluated in all the full-face H & E sections from 897 consecutive TNBC (i.e. tumors with >1{\%} of ER and PgR immunoreactivity and absence of HER2 overexpression or amplification) patients diagnosed and treated at the European Institute of Oncology between 1995 and 2010 (median follow-up 8.2 years, range 6 months to 18 years). All mononuclear cells were evaluated in the stromal area within the borders of the invasive tumor, reported as a percentage value and treated as a continuous variable in survival analysis. Results: The median percentage of TILs was 20{\%}, and 21.9{\%} of the cases had =50{\%} (lymphocyte predominant breast cancer, LPBC) TILs. At univariable survival analysis, TILs were a significant predictor of better disease-free survival (DFS), distant disease-free survival (DDFS) and overall survival (OS) (P <0.0001). Multivariable analysis confirmed that each 10{\%} increase in TILs strongly predicted better survival, independent of patients' age, lymph node status, tumor size, histological grade, peritumoral vascular invasion and Ki-67 labeling index. Patients with LPBC had a 10-year survival rate of 71{\%}, 84{\%} and 96{\%} for DFS, DDFS and OS, respectively. Stratified analysis revealed a positive correlation between TILs and OS across all the subgroups analyzed. Conclusion: Our data support the analytical validity of the recently issued TILs evaluation guidelines in the clinical practice.",
keywords = "Breast, Cancer, Chemotherapy, Survival, Triple negative, Tumor-infiltrating lymphocytes",
author = "Giancarlo Pruneri and A. Vingiani and V. Bagnardi and N. Rotmensz and {De Rose}, Angela and A. Palazzo and Colleoni, {Marco Angelo} and A. Goldhirsch and G. Viale",
year = "2016",
month = "2",
day = "1",
doi = "10.1093/annonc/mdv571",
language = "English",
volume = "27",
pages = "249--256",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "NLM (Medline)",
number = "2",

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TY - JOUR

T1 - Clinical validity of tumor-infiltrating lymphocytes analysis in patients with triple-negative breast cancer

AU - Pruneri, Giancarlo

AU - Vingiani, A.

AU - Bagnardi, V.

AU - Rotmensz, N.

AU - De Rose, Angela

AU - Palazzo, A.

AU - Colleoni, Marco Angelo

AU - Goldhirsch, A.

AU - Viale, G.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - Background: Although tumor-infiltrating lymphocytes (TILs) have been associated with a favorable prognosis in triplenegative breast cancer (TNBC) patients, this marker is not currently considered robust enough for entering the clinical practice. In the present study, we assessed the clinical validity of the guidelines recently issued by the International TIL Working Group in a large retrospective series of well-annotated TNBC patients. Patients and methods: TILs were evaluated in all the full-face H & E sections from 897 consecutive TNBC (i.e. tumors with >1% of ER and PgR immunoreactivity and absence of HER2 overexpression or amplification) patients diagnosed and treated at the European Institute of Oncology between 1995 and 2010 (median follow-up 8.2 years, range 6 months to 18 years). All mononuclear cells were evaluated in the stromal area within the borders of the invasive tumor, reported as a percentage value and treated as a continuous variable in survival analysis. Results: The median percentage of TILs was 20%, and 21.9% of the cases had =50% (lymphocyte predominant breast cancer, LPBC) TILs. At univariable survival analysis, TILs were a significant predictor of better disease-free survival (DFS), distant disease-free survival (DDFS) and overall survival (OS) (P <0.0001). Multivariable analysis confirmed that each 10% increase in TILs strongly predicted better survival, independent of patients' age, lymph node status, tumor size, histological grade, peritumoral vascular invasion and Ki-67 labeling index. Patients with LPBC had a 10-year survival rate of 71%, 84% and 96% for DFS, DDFS and OS, respectively. Stratified analysis revealed a positive correlation between TILs and OS across all the subgroups analyzed. Conclusion: Our data support the analytical validity of the recently issued TILs evaluation guidelines in the clinical practice.

AB - Background: Although tumor-infiltrating lymphocytes (TILs) have been associated with a favorable prognosis in triplenegative breast cancer (TNBC) patients, this marker is not currently considered robust enough for entering the clinical practice. In the present study, we assessed the clinical validity of the guidelines recently issued by the International TIL Working Group in a large retrospective series of well-annotated TNBC patients. Patients and methods: TILs were evaluated in all the full-face H & E sections from 897 consecutive TNBC (i.e. tumors with >1% of ER and PgR immunoreactivity and absence of HER2 overexpression or amplification) patients diagnosed and treated at the European Institute of Oncology between 1995 and 2010 (median follow-up 8.2 years, range 6 months to 18 years). All mononuclear cells were evaluated in the stromal area within the borders of the invasive tumor, reported as a percentage value and treated as a continuous variable in survival analysis. Results: The median percentage of TILs was 20%, and 21.9% of the cases had =50% (lymphocyte predominant breast cancer, LPBC) TILs. At univariable survival analysis, TILs were a significant predictor of better disease-free survival (DFS), distant disease-free survival (DDFS) and overall survival (OS) (P <0.0001). Multivariable analysis confirmed that each 10% increase in TILs strongly predicted better survival, independent of patients' age, lymph node status, tumor size, histological grade, peritumoral vascular invasion and Ki-67 labeling index. Patients with LPBC had a 10-year survival rate of 71%, 84% and 96% for DFS, DDFS and OS, respectively. Stratified analysis revealed a positive correlation between TILs and OS across all the subgroups analyzed. Conclusion: Our data support the analytical validity of the recently issued TILs evaluation guidelines in the clinical practice.

KW - Breast

KW - Cancer

KW - Chemotherapy

KW - Survival

KW - Triple negative

KW - Tumor-infiltrating lymphocytes

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DO - 10.1093/annonc/mdv571

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