Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

Kos, Z. et al. (2020) Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer. npj Breast Cancer, 6, 17. (doi: 10.1038/s41523-020-0156-0) (PMID:32411819) (PMCID:PMC7217863)

Abstract

Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls.

• Item Type: Articles
• Additional Information: R.S. is supported by a grant from the Breast Cancer Research Foundation (BCRF, grant No. 17-194). S.L. is supported by the National Breast Cancer Foundation of Australia Endowed Chair (NBCF-17-001) and the Breast Cancer Research Foundation, New York (BCRF-19-102). S.G. is supported by Susan G Komen Foundation (CCR18547966) and a Young investigator Grant from Breast Cancer Alliance. T.O.N. receives funding support from the Canadian Cancer Society. A.M. acknowledges research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award numbers 1U24CA199374-01, R01CA202752-01A1, R01CA208236-01A1, R01 CA216579-01A1, R01 CA220581-01A1, 1U01 CA239055-01, National Center for Research Resources under award number 1 C06 RR12463-01, VA Merit Review Award IBX004121A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, the DOD Prostate Cancer Idea Development Award (W81XWH-15-1-0558), the DOD Lung Cancer Investigator-Initiated Translational Research Award (W81XWH-18-1-0440), the DOD Peer Reviewed Cancer Research Program (W81XWH-16-1-0329), the Ohio Third Frontier Technology Validation Fund and the Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering and the Clinical and Translational Science Award Program (CTSA) at Case Western Reserve University. J.S. received funding from NCI grants UG3CA225021 and U24CA215109. C.S. is a Royal Society Napier Research Professor; this work was supported by the Francis Crick Institute that receives its core funding from Cancer Research UK (FC001169, FC001202), the UK Medical Research Council (FC001169, FC001202), and the Wellcome Trust (FC001169, FC001202); C.S. is also funded by Cancer Research UK (TRACERx and CRUK Cancer Immunotherapy Catalyst Network), the CRUK Lung Cancer Centre of Excellence, Stand Up 2 Cancer (SU2C), the Rosetrees Trust, Butterfield and Stoneygate Trusts, NovoNordisk Foundation (ID16584), the Prostate Cancer Foundation, the Breast Cancer Research Foundation (BCRF); the research leading to these results has received funding from the European Research Council (ERC) under the European Union’s Seventh Framework Programme (FP7/2007-2013) Consolidator Grant (FP7-THESEUS-617844), European Commission ITN (FP7-PloidyNet 607722), ERC Advanced Grant (PROTEUS) has received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 835297), Chromavision—this project has received funding from the European’s Union Horizon 2020 research and innovation programme (grant agreement No. 665233); support was also provided to C.S. by the National Institute for Health Research, the University College London Hospitals Biomedical Research Centre, and the Cancer Research UK University College London Experimental Cancer Medicine Centre. R.K. and K.P.-G. acknowledge research leading to or reported in this publication was supported by NCI U10CA180868, -180822, UG1-189867, and U24-196067 the Breast Cancer Research Foundation and Genentech.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Le Quesne, Professor John
• Authors: Kos, Z., Roblin, E., Kim, R. S., Michiels, S., Gallas, B. D., Chen, W., van de Vijver, K. K., Goel, S., Adams, S., Demaria, S., Viale, G., Nielsen, T. O., Badve, S. S., Symmans, W. F., Sotiriou, C., Rimm, D. L., Hewitt, S., Denkert, C., Loibl, S., Luen, S. J., Bartlett, J. M. S., Savas, P., Pruneri, G., Dillon, D. A., Cheang, M. C. U., Tutt, A., Hall, J. A., Kok, M., Horlings, H. M., Madabhushi, A., van der Laak, J., Ciompi, F., Laenkholm, A.-V., Bellolio, E., Gruosso, T., Fox, S. B., Araya, J. C., Floris, G., Hudeček, J., Voorwerk, L., Beck, A. H., Kerner, J., Larsimont, D., Declercq, S., Van den Eynden, G., Pusztai, L., Ehinger, A., Yang, W., AbdulJabbar, K., Yuan, Y., Singh, R., Hiley, C., Bakir, M. a., Lazar, A. J., Naber, S., Wienert, S., Castillo, M., Curigliano, G., Dieci, M.-V., André, F., Swanton, C., Reis-Filho, J., Sparano, J., Balslev, E., Chen, I.-C., Stovgaard, E. I. S., Pogue-Geile, K., Blenman, K. R. M., Penault-Llorca, F., Schnitt, S., Lakhani, S. R., Vincent-Salomon, A., Rojo, F., Braybrooke, J. P., Hanna, M. G., Soler-Monsó, M. T., Bethmann, D., Castaneda, C. A., Willard-Gallo, K., Sharma, A., Lien, H.-C., Fineberg, S., Thagaard, J., Comerma, L., Gonzalez-Ericsson, P., Brogi, E., Loi, S., Saltz, J., Klaushen, F., Cooper, L., Amgad, M., Moore, D. A., Salgado, R., the International Immuno-Oncology Biomarker Working Group, ., and ,
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: npj Breast Cancer
• Publisher: Nature Publishing Group
• ISSN: 2374-4677
• ISSN (Online): 2374-4677
• Copyright Holders: Copyright © The Authors 2020
• First Published: First published in npj Breast Cancer 6:17
• Publisher Policy: Reproduced under a Creative Commons licence