Literature DB >> 33574291

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

Zuzana Kos1, Elvire Roblin2,3, Rim S Kim4, Stefan Michiels2,3, Brandon D Gallas5, Weijie Chen5, Koen K van de Vijver6,7, Shom Goel8,9, Sylvia Adams10, Sandra Demaria11, Giuseppe Viale12, Torsten O Nielsen13, Sunil S Badve14, W Fraser Symmans15, Christos Sotiriou16, David L Rimm17, Stephen Hewitt18, Carsten Denkert19, Sibylle Loibl20, Stephen J Luen9,21, John M S Bartlett22,23, Peter Savas9,21, Giancarlo Pruneri24, Deborah A Dillon25,26, Maggie Chon U Cheang27, Andrew Tutt28, Jacqueline A Hall29, Marleen Kok30, Hugo M Horlings6,31, Anant Madabhushi32,33, Jeroen van der Laak34, Francesco Ciompi34, Anne-Vibeke Laenkholm35, Enrique Bellolio36, Tina Gruosso37, Stephen B Fox8,38, Juan Carlos Araya39, Giuseppe Floris40, Jan Hudeček41, Leonie Voorwerk42, Andrew H Beck43, Jen Kerner43, Denis Larsimont44, Sabine Declercq45, Gert Van den Eynden45, Lajos Pusztai46, Anna Ehinger47, Wentao Yang48, Khalid AbdulJabbar49, Yinyin Yuan49, Rajendra Singh50, Crispin Hiley51, Maise Al Bakir51, Alexander J Lazar52, Stephen Naber53, Stephan Wienert54, Miluska Castillo55, Giuseppe Curigliano56, Maria-Vittoria Dieci57,58, Fabrice André59, Charles Swanton51,60, Jorge Reis-Filho61,62, Joseph Sparano63, Eva Balslev64, I-Chun Chen65,66,67, Elisabeth Ida Specht Stovgaard64, Katherine Pogue-Geile4, Kim R M Blenman46, Frédérique Penault-Llorca68, Stuart Schnitt25, Sunil R Lakhani69, Anne Vincent-Salomon70, Federico Rojo71,72, Jeremy P Braybrooke73, Matthew G Hanna61, M Teresa Soler-Monsó74, Daniel Bethmann75, Carlos A Castaneda55, Karen Willard-Gallo76, Ashish Sharma77, Huang-Chun Lien78, Susan Fineberg79, Jeppe Thagaard80, Laura Comerma72,81, Paula Gonzalez-Ericsson82, Edi Brogi61, Sherene Loi9,21, Joel Saltz83, Frederick Klaushen84, Lee Cooper85, Mohamed Amgad86, David A Moore87,88, Roberto Salgado21,45.   

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 .

Year:  2020        PMID: 33574291     DOI: 10.1038/s41523-020-0156-0

Source DB:  PubMed          Journal:  NPJ Breast Cancer        ISSN: 2374-4677


  38 in total

1.  Prognostic and predictive value of tumor-infiltrating lymphocytes in two phase III randomized adjuvant breast cancer trials.

Authors:  M V Dieci; M C Mathieu; V Guarneri; P Conte; S Delaloge; F Andre; A Goubar
Journal:  Ann Oncol       Date:  2015-05-20       Impact factor: 32.976

2.  The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014.

Authors:  R Salgado; C Denkert; S Demaria; N Sirtaine; F Klauschen; G Pruneri; S Wienert; G Van den Eynden; F L Baehner; F Penault-Llorca; E A Perez; E A Thompson; W F Symmans; A L Richardson; J Brock; C Criscitiello; H Bailey; M Ignatiadis; G Floris; J Sparano; Z Kos; T Nielsen; D L Rimm; K H Allison; J S Reis-Filho; S Loibl; C Sotiriou; G Viale; S Badve; S Adams; K Willard-Gallo; S Loi
Journal:  Ann Oncol       Date:  2014-09-11       Impact factor: 32.976

3.  Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial.

Authors:  S Loi; S Michiels; R Salgado; N Sirtaine; V Jose; D Fumagalli; P-L Kellokumpu-Lehtinen; P Bono; V Kataja; C Desmedt; M J Piccart; S Loibl; C Denkert; M J Smyth; H Joensuu; C Sotiriou
Journal:  Ann Oncol       Date:  2014-03-07       Impact factor: 32.976

4.  Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy.

Authors:  Carsten Denkert; Gunter von Minckwitz; Silvia Darb-Esfahani; Bianca Lederer; Barbara I Heppner; Karsten E Weber; Jan Budczies; Jens Huober; Frederick Klauschen; Jenny Furlanetto; Wolfgang D Schmitt; Jens-Uwe Blohmer; Thomas Karn; Berit M Pfitzner; Sherko Kümmel; Knut Engels; Andreas Schneeweiss; Arndt Hartmann; Aurelia Noske; Peter A Fasching; Christian Jackisch; Marion van Mackelenbergh; Peter Sinn; Christian Schem; Claus Hanusch; Michael Untch; Sibylle Loibl
Journal:  Lancet Oncol       Date:  2017-12-07       Impact factor: 41.316

5.  Tumor-Infiltrating Lymphocytes and Prognosis: A Pooled Individual Patient Analysis of Early-Stage Triple-Negative Breast Cancers.

Authors:  Sherene Loi; Damien Drubay; Sylvia Adams; Giancarlo Pruneri; Prudence A Francis; Magali Lacroix-Triki; Heikki Joensuu; Maria Vittoria Dieci; Sunil Badve; Sandra Demaria; Robert Gray; Elisabetta Munzone; Jerome Lemonnier; Christos Sotiriou; Martine J Piccart; Pirkko-Liisa Kellokumpu-Lehtinen; Andrea Vingiani; Kathryn Gray; Fabrice Andre; Carsten Denkert; Roberto Salgado; Stefan Michiels
Journal:  J Clin Oncol       Date:  2019-01-16       Impact factor: 44.544

6.  Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02-98.

Authors:  Sherene Loi; Nicolas Sirtaine; Fanny Piette; Roberto Salgado; Giuseppe Viale; Françoise Van Eenoo; Ghizlane Rouas; Prudence Francis; John P A Crown; Erika Hitre; Evandro de Azambuja; Emmanuel Quinaux; Angelo Di Leo; Stefan Michiels; Martine J Piccart; Christos Sotiriou
Journal:  J Clin Oncol       Date:  2013-01-22       Impact factor: 44.544

7.  Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer.

Authors:  Carsten Denkert; Sibylle Loibl; Aurelia Noske; Marc Roller; Berit Maria Müller; Martina Komor; Jan Budczies; Silvia Darb-Esfahani; Ralf Kronenwett; Claus Hanusch; Christian von Törne; Wilko Weichert; Knut Engels; Christine Solbach; Iris Schrader; Manfred Dietel; Gunter von Minckwitz
Journal:  J Clin Oncol       Date:  2009-11-16       Impact factor: 44.544

Review 8.  Breast cancer genomics and immuno-oncological markers to guide immune therapies.

Authors:  D Hammerl; M Smid; A M Timmermans; S Sleijfer; J W M Martens; R Debets
Journal:  Semin Cancer Biol       Date:  2017-11-06       Impact factor: 15.707

Review 9.  Clinical relevance of host immunity in breast cancer: from TILs to the clinic.

Authors:  Peter Savas; Roberto Salgado; Carsten Denkert; Christos Sotiriou; Phillip K Darcy; Mark J Smyth; Sherene Loi
Journal:  Nat Rev Clin Oncol       Date:  2015-12-15       Impact factor: 66.675

10.  Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199.

Authors:  Sylvia Adams; Robert J Gray; Sandra Demaria; Lori Goldstein; Edith A Perez; Lawrence N Shulman; Silvana Martino; Molin Wang; Vicky E Jones; Thomas J Saphner; Antonio C Wolff; William C Wood; Nancy E Davidson; George W Sledge; Joseph A Sparano; Sunil S Badve
Journal:  J Clin Oncol       Date:  2014-09-20       Impact factor: 44.544

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