Reproducibility and predictive value of scoring stromal tumour infiltrating lymphocytes in triple-negative breast cancer : a multi-institutional study
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Date
2018-08-01
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Abstract
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.
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Funding Information: Funding This work was funded by Breast Cancer Now (2013MayPR019 and 2015NovPhD643), Science Foundation Ireland (17/CDA/4638) and Irish Cancer Society (SG); Breast Cancer Research (EW), and an NUI Galway School of Medicine Scholarship (EW). Publisher Copyright: © 2018, The Author(s).
Keywords
Inter-observer agreement, Neoadjuvant chemotherapy, Pathological complete response, sTILs, Stromal tumour infiltrating lymphocytes, Triple-negative breast cancer, 3.1 Basic medicine, 3.2 Clinical medicine, 1.1. Scientific article indexed in Web of Science and/or Scopus database, Oncology, Cancer Research, SDG 3 - Good Health and Well-being
Citation
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, Walsh, E M, Zolota, V, Glynn, S A & Callagy, G 2018, 'Reproducibility and predictive value of scoring stromal tumour infiltrating lymphocytes in triple-negative breast cancer : a multi-institutional study', Breast Cancer Research and Treatment, vol. 171, no. 1, pp. 1-9. https://doi.org/10.1007/s10549-018-4825-8