Reproducibility and predictive value of scoring stromal tumour infiltrating lymphocytes in triple-negative breast cancer: a multi-institutional study

Mark O’Loughlin, Xavier Andreu, Simonetta Bianchi, Ewa Chemielik, Alicia Cordoba, G. Cserni, Paulo Figueiredo, Giuseppe Floris, Maria P. Foschini, Päivi Heikkilä, J. Kulka, Inta Liepniece-Karele, Peter Regitnig, Angelika Reiner, Ales Ryska, Anna Sapino, Aliaa Shalaby, Elisabeth Specht Stovgaard, Cecily Quinn, Elaine M. WalshVicky Zolota, Sharon A. Glynn, Grace Callagy

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5 Citations (Scopus)


Background: Several studies have demonstrated a prognostic role for stromal tumour infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC). The reproducibility of scoring sTILs is variable with potentially excellent concordance being achievable using a software tool. We examined agreement between breast pathologists across Europe scoring sTILs on H&E-stained sections without software, an approach that is easily applied in clinical practice. The association between sTILs and response to anthracycline-taxane NACT was also examined. Methodology: Pathologists from the European Working Group for Breast Screening Pathology scored sTILs in 84 slides from 75 TNBCs using the immune-oncology biomarker working group guidance in two circulations. There were 16 participants in the first and 19 in the second circulation. Results: Moderate agreement was achieved for absolute sTILs scores (intraclass correlation coefficient (ICC) = 0.683, 95% CI 0.601–0.767, p-value < 0.001). Agreement was less when a 25% threshold was used (ICC 0.509, 95% CI 0.416–0.614, p-value < 0.001) and for lymphocyte predominant breast cancer (LPBC) (ICC 0.504, 95% CI 0.412–0.610, p-value < 0.001). Intra-observer agreement was strong for absolute sTIL values (Spearman ρ = 0.727); fair for sTILs ≥ 25% (κ = 0.53) and for LPBC (κ = 0.49), but poor for sTILs as 10% increments (κ = 0.24). Increasing sTILs was significantly associated with an increased likelihood of a pathological complete response (pCR) on multivariable analysis. Conclusion: Increasing sTILs in TNBCs improves the likelihood of a pCR. However, inter-observer agreement is such that H&E-based assessment is not sufficiently reproducible for clinical application. Other methodologies should be explored, but may be at the cost of ease of application.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalBreast Cancer Research and Treatment
Publication statusAccepted/In press - May 17 2018



  • Inter-observer agreement
  • Neoadjuvant chemotherapy
  • Pathological complete response
  • sTILs
  • Stromal tumour infiltrating lymphocytes
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

O’Loughlin, M., Andreu, X., Bianchi, S., Chemielik, E., Cordoba, A., Cserni, G., Figueiredo, P., Floris, G., Foschini, M. P., Heikkilä, P., Kulka, J., Liepniece-Karele, I., Regitnig, P., Reiner, A., Ryska, A., Sapino, A., Shalaby, A., Stovgaard, E. S., Quinn, C., ... Callagy, G. (Accepted/In press). Reproducibility and predictive value of scoring stromal tumour infiltrating lymphocytes in triple-negative breast cancer: a multi-institutional study. Breast Cancer Research and Treatment, 1-9.