R Salgado1, C Denkert2, S Demaria3, N Sirtaine4, F Klauschen2, G Pruneri5, S Wienert2, G Van den Eynden6, F L Baehner7, F Penault-Llorca8, E A Perez9, E A Thompson10, W F Symmans11, A L Richardson12, J Brock13, C Criscitiello14, H Bailey15, M Ignatiadis16, G Floris17, J Sparano18, Z Kos19, T Nielsen20, D L Rimm21, K H Allison22, J S Reis-Filho23, S Loibl24, C Sotiriou16, G Viale25, S Badve26, S Adams3, K Willard-Gallo27, S Loi28. 1. Breast Cancer Translational Research Laboratory/Breast International Group, Institut Jules Bordet, Brussels Department of Pathology and TCRU, GZA, Antwerp, Belgium. 2. Institute of Pathology, Charité -University Hospital, Berlin, Germany. 3. Perlmutter Cancer Center, New York University Medical School, New York, USA. 4. Department of Pathology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. 5. European Institute of Oncology (IEO) and University of Milan, Milan, Italy. 6. Department of Pathology GZA, TCRU Hospitals and CORE Antwerp University, Antwerp, Belgium. 7. Genomic Health, Inc., Redwood City, USA University of California San Francisco, San Francisco, USA. 8. Clermont-Ferrand Biopathology, University of Auvergne, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France. 9. Division of Haematology/Medical Oncology and. 10. Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville. 11. Department of Pathology, The UT M.D. Anderson Cancer Center, Boston. 12. Department of Pathology, Brigham and Women's Hospital, Boston Department of Cancer Biology, Dana Farber Cancer Institute, Boston. 13. Department of Cancer Biology, Dana Farber Cancer Institute, Boston Department of Cancer Biology, Harvard Medical School, Boston, USA. 14. Istituto Europeo di Oncologia, Milan, Italy. 15. Genomic Health, Inc., Redwood City, USA. 16. Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels. 17. Department of Pathology, University Hospital Leuven, Leuven, Belgium. 18. Department of Medicine, Department of Obstetrics and Gynecology and Women's Health, Albert Einstein Medical Center, Bronx, USA. 19. Laboratory Medicine Program, University Health Network, University of Toronto, Toronto. 20. Department of Pathology and Laboratory Medicine, Genetic Pathology Evaluation Centre, University of British Columbia, Vancouver, Canada. 21. Department of Pathology, Yale University School of Medicine, New Haven. 22. Department of Pathology, Stanford University Medical Centre, Stanford. 23. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, USA. 24. German Breast Group, Neu-Isenburg, Germany. 25. Department of Pathology, Istituto Europeo di Oncologia, University of Milan, Milan, Italy. 26. Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, USA. 27. Molecular Immunology Unit, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. 28. Division of Research and Cancer Medicine, Peter MacCallum Cancer Centre, University of Melbourne, Victoria, Australia sherene.loi@petermac.org.
Abstract
BACKGROUND: The morphological evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer (BC) is gaining momentum as evidence strengthens for the clinical relevance of this immunological biomarker. Accumulating evidence suggests that the extent of lymphocytic infiltration in tumor tissue can be assessed as a major parameter by evaluation of hematoxylin and eosin (H&E)-stained tumor sections. TILs have been shown to provide prognostic and potentially predictive value, particularly in triple-negative and human epidermal growth factor receptor 2-overexpressing BC. DESIGN: A standardized methodology for evaluating TILs is now needed as a prerequisite for integrating this parameter in standard histopathological practice, in a research setting as well as in clinical trials. This article reviews current data on the clinical validity and utility of TILs in BC in an effort to foster better knowledge and insight in this rapidly evolving field, and to develop a standardized methodology for visual assessment on H&E sections, acknowledging the future potential of molecular/multiplexed approaches. CONCLUSIONS: The methodology provided is sufficiently detailed to offer a uniformly applied, pragmatic starting point and improve consistency and reproducibility in the measurement of TILs for future studies.
BACKGROUND: The morphological evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer (BC) is gaining momentum as evidence strengthens for the clinical relevance of this immunological biomarker. Accumulating evidence suggests that the extent of lymphocytic infiltration in tumor tissue can be assessed as a major parameter by evaluation of hematoxylin and eosin (H&E)-stained tumor sections. TILs have been shown to provide prognostic and potentially predictive value, particularly in triple-negative and human epidermal growth factor receptor 2-overexpressing BC. DESIGN: A standardized methodology for evaluating TILs is now needed as a prerequisite for integrating this parameter in standard histopathological practice, in a research setting as well as in clinical trials. This article reviews current data on the clinical validity and utility of TILs in BC in an effort to foster better knowledge and insight in this rapidly evolving field, and to develop a standardized methodology for visual assessment on H&E sections, acknowledging the future potential of molecular/multiplexed approaches. CONCLUSIONS: The methodology provided is sufficiently detailed to offer a uniformly applied, pragmatic starting point and improve consistency and reproducibility in the measurement of TILs for future studies.
Authors: Helena Hornychova; Bohuslav Melichar; Marketa Tomsova; Jindøiska Mergancova; Hana Urminska; Ales Ryska Journal: Cancer Invest Date: 2008-12 Impact factor: 2.176
Authors: Jason R Brown; Hallie Wimberly; Donald R Lannin; Christian Nixon; David L Rimm; Veerle Bossuyt Journal: Clin Cancer Res Date: 2014-09-25 Impact factor: 12.531
Authors: Sahar M A Mahmoud; Emma Claire Paish; Desmond G Powe; R Douglas Macmillan; Matthew J Grainge; Andrew H S Lee; Ian O Ellis; Andrew R Green Journal: J Clin Oncol Date: 2011-04-11 Impact factor: 44.544
Authors: Kurt A Schalper; Jason Brown; Daniel Carvajal-Hausdorf; Joseph McLaughlin; Vamsidhar Velcheti; Konstantinos N Syrigos; Roy S Herbst; David L Rimm Journal: J Natl Cancer Inst Date: 2015-02-03 Impact factor: 11.816
Authors: H R Ali; E Provenzano; S-J Dawson; F M Blows; B Liu; M Shah; H M Earl; C J Poole; L Hiller; J A Dunn; S J Bowden; C Twelves; J M S Bartlett; S M A Mahmoud; E Rakha; I O Ellis; S Liu; D Gao; T O Nielsen; P D P Pharoah; C Caldas Journal: Ann Oncol Date: 2014-06-09 Impact factor: 32.976
Authors: Shona Hendry; Roberto Salgado; Thomas Gevaert; Prudence A Russell; Tom John; Bibhusal Thapa; Michael Christie; Koen van de Vijver; M V Estrada; Paula I Gonzalez-Ericsson; Melinda Sanders; Benjamin Solomon; Cinzia Solinas; Gert G G M Van den Eynden; Yves Allory; Matthias Preusser; Johannes Hainfellner; Giancarlo Pruneri; Andrea Vingiani; Sandra Demaria; Fraser Symmans; Paolo Nuciforo; Laura Comerma; E A Thompson; Sunil Lakhani; Seong-Rim Kim; Stuart Schnitt; Cecile Colpaert; Christos Sotiriou; Stefan J Scherer; Michail Ignatiadis; Sunil Badve; Robert H Pierce; Giuseppe Viale; Nicolas Sirtaine; Frederique Penault-Llorca; Tomohagu Sugie; Susan Fineberg; Soonmyung Paik; Ashok Srinivasan; Andrea Richardson; Yihong Wang; Ewa Chmielik; Jane Brock; Douglas B Johnson; Justin Balko; Stephan Wienert; Veerle Bossuyt; Stefan Michiels; Nils Ternes; Nicole Burchardi; Stephen J Luen; Peter Savas; Frederick Klauschen; Peter H Watson; Brad H Nelson; Carmen Criscitiello; Sandra O'Toole; Denis Larsimont; Roland de Wind; Giuseppe Curigliano; Fabrice André; Magali Lacroix-Triki; Mark van de Vijver; Federico Rojo; Giuseppe Floris; Shahinaz Bedri; Joseph Sparano; David Rimm; Torsten Nielsen; Zuzana Kos; Stephen Hewitt; Baljit Singh; Gelareh Farshid; Sibylle Loibl; Kimberly H Allison; Nadine Tung; Sylvia Adams; Karen Willard-Gallo; Hugo M Horlings; Leena Gandhi; Andre Moreira; Fred Hirsch; Maria V Dieci; Maria Urbanowicz; Iva Brcic; Konstanty Korski; Fabien Gaire; Hartmut Koeppen; Amy Lo; Jennifer Giltnane; Marlon C Rebelatto; Keith E Steele; Jiping Zha; Kenneth Emancipator; Jonathan W Juco; Carsten Denkert; Jorge Reis-Filho; Sherene Loi; Stephen B Fox Journal: Adv Anat Pathol Date: 2017-11 Impact factor: 3.875
Authors: Álvaro de Mingo Pulido; Alycia Gardner; Shandi Hiebler; Hatem Soliman; Hope S Rugo; Matthew F Krummel; Lisa M Coussens; Brian Ruffell Journal: Cancer Cell Date: 2018-01-08 Impact factor: 31.743
Authors: Innocenza Palaia; Federica Tomao; Anna DI Pinto; Angelina Pernazza; Giusi Santangelo; Nicoletta D'Alessandris; Lucia Manganaro; Antonio Arno; Violante DI Donato; Giorgia Perniola; Carlo Della Rocca; Pierluigi Benedetti Panici Journal: In Vivo Date: 2021 Mar-Apr Impact factor: 2.155
Authors: Stephen J Luen; Roberto Salgado; Stephen Fox; Peter Savas; Jennifer Eng-Wong; Emma Clark; Astrid Kiermaier; Sandra M Swain; Jose Baselga; Stefan Michiels; Sherene Loi Journal: Lancet Oncol Date: 2016-12-07 Impact factor: 41.316