Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer.
Zuzana Kos,
Elvire Roblin,
Rim S Kim,
Stefan Michiels,
Brandon D Gallas,
Weijie Chen,
Koen K van de Vijver,
Shom Goel,
Sylvia Adams,
Sandra Demaria,
Giuseppe Viale,
Torsten O Nielsen,
Sunil S Badve,
W Fraser Symmans,
Christos Sotiriou,
David L Rimm,
Stephen Hewitt,
Carsten Denkert,
Sibylle Loibl,
Stephen J Luen,
John M S Bartlett,
Peter Savas,
Giancarlo Pruneri,
Deborah A Dillon,
Maggie Chon U Cheang,
Andrew Tutt,
Jacqueline A Hall,
Marleen Kok,
Hugo M Horlings,
Anant Madabhushi,
Jeroen van der Laak,
Francesco Ciompi,
Anne-Vibeke Laenkholm,
Enrique Bellolio,
Tina Gruosso,
Stephen B Fox,
Juan Carlos Araya,
Giuseppe Floris,
Jan Hudeček,
Leonie Voorwerk,
Andrew H Beck,
Jen Kerner,
Denis Larsimont,
Sabine Declercq,
Gert Van den Eynden,
Lajos Pusztai,
Anna Ehinger,
Wentao Yang,
Khalid AbdulJabbar,
Yinyin Yuan,
Rajendra Singh,
Crispin Hiley,
Maise Al Bakir,
Alexander J Lazar,
Stephen Naber,
Stephan Wienert,
Miluska Castillo,
Giuseppe Curigliano,
Maria-Vittoria Dieci,
Fabrice André,
Charles Swanton,
Jorge Reis-Filho,
Joseph Sparano,
Eva Balslev,
I-Chun Chen,
Elisabeth Ida Specht Stovgaard,
Katherine Pogue-Geile,
Kim R M Blenman,
Frédérique Penault-Llorca,
Stuart Schnitt,
Sunil R Lakhani,
Anne Vincent-Salomon,
Federico Rojo,
Jeremy P Braybrooke,
Matthew G Hanna,
M Teresa Soler-Monsó,
Daniel Bethmann,
Carlos A Castaneda,
Karen Willard-Gallo,
Ashish Sharma,
Huang-Chun Lien,
Susan Fineberg,
Jeppe Thagaard,
Laura Comerma,
Paula Gonzalez-Ericsson,
Edi Brogi,
Sherene Loi,
Joel Saltz,
Frederick Klaushen,
Lee Cooper,
Mohamed Amgad,
David A Moore,
Roberto Salgado,
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.