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

Zuzana Kos Elvire Roblin Rim Kim Stefan Michiels 1 Brandon Gallas Weijie Chen Koen van de Vijver Shom Goel Sylvia Adams Sandra Demaria Giuseppe Viale 2 Torsten Nielsen Sunil Badve W Fraser Symmans Christos Sotiriou 3 David Rimm Stephen Hewitt Carsten Denkert 4 Sibylle Loibl 5 Stephen Luen John Bartlett 6 Peter Savas Giancarlo Pruneri 7 Deborah Dillon Maggie Chon U Cheang Andrew Tutt 8 Jacqueline Hall Marleen Kok 9 Hugo Horlings 10 Anant Madabhushi Jeroen van der Laak Francesco Ciompi Anne-Vibeke Laenkholm 11 Enrique Bellolio Tina Gruosso 12 Stephen Fox Juan Carlos Araya Giuseppe Floris Jan Hudeček Leonie Voorwerk Andrew Beck Jen Kerner Denis Larsimont 3 Sabine Declercq Gert van den Eynden Lajos Pusztai 13 Anna Ehinger 14 Wentao Yang Khalid Abduljabbar Yinyin Yuan Rajendra Singh Crispin Hiley Maise Al Bakir Alexander Lazar 15 Stephen Naber Stephan Wienert Miluska Castillo Giuseppe Curigliano 16 Maria-Vittoria Dieci Fabrice André 17 Charles Swanton 18 Jorge Reis-Filho 19 Joseph Sparano Eva Balslev 20 I-Chun Chen Elisabeth Ida Specht Stovgaard Katherine Pogue-Geile Kim Blenman Frédérique Penault-Llorca 21, 22 Stuart Schnitt Sunil Lakhani 23 Anne Vincent-Salomon 24 Federico Rojo 25 Jeremy Braybrooke Matthew Hanna M Teresa Soler-Monsó Daniel Bethmann Carlos Castaneda 26 Karen Willard-Gallo Ashish Sharma 27 Huang-Chun Lien Susan Fineberg Jeppe Thagaard Laura Comerma Paula Gonzalez-Ericsson Edi Brogi Sherene Loi 28 Joel Saltz Frederick Klaushen Lee Cooper Mohamed Amgad David Moore 29 Roberto Salgado 28 W. Fraser Symmans Maggie Chon U. Cheang M. Teresa Soler-Monsó
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
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Submitted on : Friday, June 26, 2020 - 3:11:46 PM
Last modification on : Thursday, July 9, 2020 - 3:36:28 AM

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Zuzana Kos, Elvire Roblin, Rim Kim, Stefan Michiels, Brandon Gallas, et al.. Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer. npj Breast Cancer, 2020, 6 (1), pp.17. ⟨10.1038/s41523-020-0156-0⟩. ⟨hal-02882217⟩



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