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Pitfalls in Assessing Stromal Tumor Infiltrating Lymphocytes (Stils) in Breast Cancer Publisher



Kos Z1 ; Roblin E2, 3 ; Kim RS4 ; Michiels S2, 3 ; Gallas BD5 ; Chen W5 ; Van De Vijver KK8, 9 ; Goel S10, 11 ; Adams S12 ; Demaria S13 ; Viale G14 ; Nielsen TO15 ; Badve SS16 ; Symmans WF17 Show All Authors
Authors
  1. Kos Z1
  2. Roblin E2, 3
  3. Kim RS4
  4. Michiels S2, 3
  5. Gallas BD5
  6. Chen W5
  7. Van De Vijver KK8, 9
  8. Goel S10, 11
  9. Adams S12
  10. Demaria S13
  11. Viale G14
  12. Nielsen TO15
  13. Badve SS16
  14. Symmans WF17
  15. Sotiriou C18
  16. Rimm DL19
  17. Hewitt S20
  18. Denkert C21
  19. Loibl S22
  20. Luen SJ11, 23
  21. Bartlett JMS24, 25
  22. Savas P11, 23
  23. Pruneri G26
  24. Dillon DA27, 28
  25. Cheang MCU29
  26. Tutt A30
  27. Hall JA31
  28. Kok M32
  29. Horlings HM8, 33
  30. Madabhushi A34, 35
  31. Van Der Laak J36
  32. Ciompi F36
  33. Laenkholm AV37
  34. Bellolio E38
  35. Gruosso T39
  36. Fox SB10, 40
  37. Araya JC41
  38. Floris G42
  39. Hudecek J43
  40. Voorwerk L44
  41. Beck AH45
  42. Kerner J45
  43. Larsimont D46
  44. Declercq S47
  45. Van Den Eynden G47
  46. Pusztai L48
  47. Ehinger A49
  48. Yang W50
  49. Abduljabbar K51
  50. Yuan Y51
  51. Singh R53
  52. Hiley C54
  53. Bakir M54
  54. Lazar AJ55
  55. Naber S56
  56. Wienert S57
  57. Castillo M58
  58. Curigliano G59
  59. Dieci MV60, 61
  60. Andre F62
  61. Swanton C54, 63
  62. Reisfilho J64, 65
  63. Sparano J66
  64. Balslev E67
  65. Chen IC68, 69, 70
  66. Stovgaard EIS67
  67. Poguegeile K4
  68. Blenman KRM48
  69. Penaultllorca F71
  70. Schnitt S27
  71. Lakhani SR72
  72. Vincentsalomon A73
  73. Rojo F74, 75
  74. Braybrooke JP76
  75. Hanna MG64
  76. Solermonso MT77
  77. Bethmann D78
  78. Castaneda CA58
  79. Willardgallo K79
  80. Sharma A80
  81. Lien HC81
  82. Fineberg S82
  83. Thagaard J83
  84. Comerma L75, 85
  85. Gonzalezericsson P86
  86. Brogi E64
  87. Loi S11, 23
  88. Saltz J87
  89. Klaushen F88
  90. Cooper L89
  91. Amgad M90
  92. Moore DA91, 92
  93. Salgado R23, 47
  94. Hyytiainen A93
  95. Hida AI94
  96. Thompson A95
  97. Lefevre A96
  98. Gown A97
  99. Lo A98
  100. Sapino A99
  101. Moreira AM100
  102. Richardson A101
  103. Vingiani A102
  104. Bellizzi AM103
  105. Guerrero A104
  106. Grigoriadis A105, 106
  107. Garridocastro AC107, 108
  108. Ciminomathews A109
  109. Srinivasan A4
  110. Acs B110
  111. Singh B111
  112. Calhoun B112
  113. Haibekans B113
  114. Solomon B11
  115. Thapa B114
  116. Nelson BH115
  117. Ballesteroesmerino C116
  118. Criscitiello C117
  119. Boeckx C96
  120. Colpaert C118
  121. Quinn C119
  122. Chennubhotla CS120
  123. Solinas C121
  124. Drubay D2, 3
  125. Sabanathan D122
  126. Peeters D123
  127. Zardavas D124
  128. Hoflmayer D125
  129. Johnson DB126
  130. Thompson EA127
  131. Perez E128
  132. Elgabry EA129
  133. Blackley EF11
  134. Reisenbichler E19
  135. Chmielik E130
  136. Gaire F131
  137. Lu FI132
  138. Azmoudehardalan F133
  139. Peale F134
  140. Hirsch FR135
  141. Acostahaab G136
  142. Farshid G137
  143. Broeckx G138
  144. Koeppen H98
  145. Haynes HR139
  146. Mcarthur H140
  147. Joensuu H141
  148. Olofsson H142
  149. Cree I143
  150. Nederlof I33
  151. Frahm I144
  152. Brcic I145
  153. Chan J146
  154. Ziai J98
  155. Brock J27
  156. Weseling J8
  157. Giltnane J98
  158. Lemonnier J147
  159. Zha J148
  160. Ribeiro J149
  161. Lennerz JK150
  162. Carter JM151
  163. Hartman J152
  164. Hainfellner J153
  165. Le Quesne J154
  166. Juco JW155
  167. Van Den Berg J8
  168. Sanchez J58
  169. Cucherousset J156
  170. Adam J157
  171. Balko JM158
  172. Saeger K159
  173. Siziopikou K160
  174. Sikorska K161
  175. Weber K22
  176. Steele KE148
  177. Emancipator K155
  178. El Bairi K162
  179. Allison KH163
  180. Korski K131
  181. Buisseret L79
  182. Shi L164
  183. Kooreman LFS165
  184. Molinero L134
  185. Estrada MV166
  186. Van Seijen M33
  187. Lacroixtriki M167
  188. Sebastian MM168
  189. Balancin ML169
  190. Mathieu MC171
  191. Van De Vijver M172
  192. Rebelatto MC148
  193. Piccart M173
  194. Goetz MP128
  195. Preusser M153
  196. Khojasteh M174
  197. Sanders ME175
  198. Regan MM108, 176
  199. Barnes M177
  200. Christie M178
  201. Misialek M179
  202. Ignatiadis M18
  203. De Maaker M33
  204. Van Bockstal M180
  205. Harbeck N181
  206. Tung N182
  207. Laudus N183
  208. Sirtaine N184
  209. Burchardi N22
  210. Ternes N2
  211. Radosevicrobin N185
  212. Gluz O186
  213. Grimm O131
  214. Nuciforo P187
  215. Jank P188
  216. Kirtani P189
  217. Watson PH15
  218. Jelinic P155
  219. Francis PA10, 11
  220. Russell PA190
  221. Pierce RH191
  222. Hills R192
  223. Leonferre R128
  224. De Wind R184
  225. Shui R50
  226. Leung S15
  227. Tabbarah S193
  228. Souza SC156
  229. Otoole S194
  230. Swain S195
  231. Dudgeon S5
  232. Willis S196
  233. Ely S197
  234. Bedri S198
  235. Irshad S199
  236. Liu S201
  237. Hendry S40
  238. Bianchi S202
  239. Braganca S203
  240. Paik S4
  241. Luz S204
  242. Gevaert T205
  243. Dalfons T64
  244. John T206
  245. Sugie T207
  246. Kurkure U174
  247. Bossuyt V150
  248. Manem V113
  249. Camaea VP208
  250. Tong W209
  251. Tran WT193
  252. Wang Y210
  253. Allory Y211
  254. Husain Z212
  255. Bagohorvath Z213
Show Affiliations
Authors Affiliations
  1. 1. Department of Pathology, BC Cancer - Vancouver, Vancouver, BC, Canada
  2. 2. Department of Biostatistics and Epidemiology, Gustave Roussy, University Paris-Saclay, Villejuif, France
  3. 3. Oncostat U1018, Inserm, University Paris-Saclay, labeled Ligue Contre le Cancer, Villejuif, France
  4. 4. National Surgical Adjuvant Breast and Bowel Project (NSABP)/NRG Oncology, Pittsburgh, PA, United States
  5. 5. Division of Imaging, Diagnostics, and Software Reliability (DIDSR)
  6. 6. Office of Science and Engineering Laboratories (OSEL)
  7. 7. Center for Devices and Radiological Health (CDRH), US Food and Drug Administration (US FDA), Silver Spring, MD, United States
  8. 8. Department of Pathology, University Hospital Antwerp, Antwerp, Belgium
  9. 9. Department of Pathology, Ghent University Hospital, Cancer Research Institute Ghent (CRIG), Ghent, Belgium
  10. 10. The Sir Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  11. 11. Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia
  12. 12. Perlmutter Cancer Center, New York University Medical School, New York, NY, United States
  13. 13. Departments of Radiation Oncology and Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, United States
  14. 14. Department of Pathology, Istituto Europeo di Oncologia, University of Milan, Milan, Italy
  15. 15. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
  16. 16. Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, United States
  17. 17. Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States
  18. 18. Department of Medical Oncology, Institut Jules Bordet, Universite Libre de Bruxelles, Brussels, Belgium
  19. 19. Department of Pathology, Yale School of Medicine, New Haven, CT, United States
  20. 20. Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, MD, United States
  21. 21. Institute of Pathology, Universitatsklinikum Gießen und Marburg GmbH, Standort Marburg and Philipps-Universitat Marburg, Marburg, Germany
  22. 22. German Breast Group, Neu-Isenburg, Germany
  23. 23. Division of Research and Cancer Medicine, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC, Australia
  24. 24. Ontario Institute for Cancer Research, Toronto, ON, Canada
  25. 25. University of Edinburgh Cancer Research Centre, Edinburgh, United Kingdom
  26. 26. Department of Pathology, IRCCS Fondazione Instituto Nazionale Tumori and University of Milan, School of Medicine, Milan, Italy
  27. 27. Department of Pathology, Brigham and Women’s Hospital, Boston, MA, United States
  28. 28. Department of Pathology, Dana Farber Cancer Institute, Boston, MA, United States
  29. 29. Institute of Cancer Research Clinical Trials and Statistics Unit, The Institute of Cancer Research, Surrey, United Kingdom
  30. 30. Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, United Kingdom
  31. 31. Vivactiv Ltd, Bellingdon, Bucks, United Kingdom
  32. 32. Department of Medical Oncology and Division of Tumor Biology & Immunology, The Netherlands Cancer Institute, Amsterdam, Netherlands
  33. 33. Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, Netherlands
  34. 34. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States
  35. 35. Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, United States
  36. 36. Computational Pathology Group, Department of Pathology, Radboud University Medical Center, Nijmegen, Netherlands
  37. 37. Department of Surgical Pathology Zealand University Hospital, Koge, Denmark
  38. 38. Departamento de Anatomia Patologica, Universidad de La Frontera, Temuco, Chile
  39. 39. Forbius, Montreal, QC, Canada
  40. 40. Department of Pathology, Peter MacCallum Cancer Centre Department of Pathology, Melbourne, VIC, Australia
  41. 41. Department of Pathology, Universidad de la Frontera, Temuco, Chile
  42. 42. KU Leuven- Univerisity of Leuven, Department of Imaging and Pathology, Laboratory of Translational Cell & Tissue Research and KU Leuven- University Hospitals Leuven, Department of Pathology, Leuven, Belgium
  43. 43. Department of Research IT, The Netherlands Cancer Institute, Amsterdam, Netherlands
  44. 44. Division of Tumor Biology & Immunology, The Netherlands Cancer Institute, Amsterdam, Netherlands
  45. 45. PathAI, Inc, Boston, MA, United States
  46. 46. Department of Pathology, Jules Bordet Institute, Brussels, Belgium
  47. 47. Department of Pathology, GZA-ZNA, Antwerp, Belgium
  48. 48. Department of Internal Medicine, Section of Medical Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT, United States
  49. 49. Department of Clinical Genetics and Pathology, Skane University Hospital, Lund University, Lund, Sweden
  50. 50. Department of Pathology, Fudan University Shanghai Cancer Centre, Shanghai, China
  51. 51. Centre for Evolution and Cancer
  52. 52. Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom
  53. 53. Icahn School of Medicine at Mt. Sinai, New York, 10029, NY, United States
  54. 54. Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, United Kingdom
  55. 55. Departments of Pathology, Genomic Medicine, Dermatology, and Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
  56. 56. Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, United States
  57. 57. Charite - Universitatsmedizin Berlin, corporate member of Freie Universitat Berlin, Humboldt-Universitat zu Berlin, and Berlin Institute of Health, Institute of Pathology, Chariteplatz 1, Berlin, 10117, Germany
  58. 58. Department of Medical Oncology and Research, Instituto Nacional de Enfermedades Neoplasicas, Lima, 15038, Peru
  59. 59. University of Milan, Istituto Europeo di Oncologia, IRCCS, Milan, Italy
  60. 60. Medical Oncology 2, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy
  61. 61. Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
  62. 62. Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France
  63. 63. Francis Crick Institute, Midland Road, London, United Kingdom
  64. 64. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United States
  65. 65. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, United States
  66. 66. Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, United States
  67. 67. Department of Pathology, Herlev and Gentofte Hospital, Herlev, Denmark
  68. 68. Department of Oncology, National Taiwan University Cancer Center, Taipei, Taiwan
  69. 69. Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
  70. 70. Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan
  71. 71. Centre de Lutte contre le cancer - Centre Jean Perrin, Clermont-Ferrand, France
  72. 72. The University of Queensland Centre for Clinical Research and Pathology Queensland, Brisbane, QLD, Australia
  73. 73. Institut Curie, Paris Sciences Lettres Universite, Inserm U934, Department of Pathology, Paris, France
  74. 74. Pathology Department, Instituto de Investigacion Sanitaria Fundacion Jimenez Diaz (IIS-FJD) - CIBERONC, Madrid, Spain
  75. 75. GEICAM-Spanish Breast Cancer Research Group, Madrid, Spain
  76. 76. Nuffield Department of Population Health, University of Oxford, Oxford and Department of Medical Oncology, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom
  77. 77. Department of Pathology, Bellvitge University Hospital, IDIBELL. Breast Unit. Catalan Institut of Oncology. L ‘Hospitalet del Llobregat’, Barcelona, 08908, Catalonia, Spain
  78. 78. University Hospital Halle (Saale), Institute of Pathology, Halle (Saale), Germany
  79. 79. Molecular Immunology Unit, Institut Jules Bordet, Universite Libre de Bruxelles, Brussels, Belgium
  80. 80. Department of Biomedical Informatics, Emory University, Atlanta, GA, United States
  81. 81. Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
  82. 82. Department of Pathology, Montefiore Medical Center and the Albert Einstein College of Medicine, Bronx, NY, United States
  83. 83. DTU Compute, Department of Applied Mathematics, Technical University of Denmark
  84. 84. Visiopharm A/S, Horsholm, Denmark
  85. 85. Pathology Department, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain
  86. 86. Breast Cancer Program, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, United States
  87. 87. Biomedical Informatics Department, Stony Brook University, Stony Brook, NY, United States
  88. 88. Institute of Pathology, Charite Universitatsmedizin Berlin, Berlin, Germany
  89. 89. Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
  90. 90. Department of Biomedical Informatics, Emory University School of Medicine, Atlanta, GA, United States
  91. 91. Department of Pathology, UCL Cancer Institute, UCL, London, United Kingdom
  92. 92. University College Hospitals NHS Trust, London, United Kingdom
  93. 93. Department of Oral and Maxillofacial Diseases, Helsinki, Finland
  94. 94. Department of Pathology, Matsuyama Shimin Hospital, Matsuyama, Japan
  95. 95. Surgical Oncology, Baylor College of Medicine, Houston, TX, United States
  96. 96. Roche Diagnostics, Machelen, Belgium
  97. 97. PhenoPath Laboratories, Seattle, WA, United States
  98. 98. Research Pathology, Genentech Inc., South San Francisco, CA, United States
  99. 99. Department of Medical Sciences, University of Torino, Italy and Candiolo Cancer Institute - FPO, IRCCS, Candiolo, Italy
  100. 100. Department of Pathology, New York University Langone Health, Center for Biospecimen Research and Development, New York, NY, United States
  101. 101. Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, United States
  102. 102. Department of Pathology, Insituto Nazionale dei Tumori, Milan, Italy
  103. 103. Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, United States
  104. 104. Department of Oncology, IVO Valencia, Valencia, Spain
  105. 105. Cancer Bioinformatics Lab, Cancer Centre at Guy’s Hospital, London, United Kingdom
  106. 106. School of Life Sciences and Medicine, King’s College London, London, United Kingdom
  107. 107. Dana-Farber Cancer Institute, Boston, MA, United States
  108. 108. Harvard Medical School, Boston, MA, United States
  109. 109. Departments of Pathology and Oncology, The Johns Hopkins Hospital, Baltimore, MD, United States
  110. 110. Department of Pathology, Karolinska Institute, Solna, Sweden
  111. 111. Department of Pathology, New York University Langone Medical Centre, New York, NY, United States
  112. 112. Department of Pathology and Laboratory Medicine, UNC School of Medicine, Chapel Hill, NC, United States
  113. 113. Bioinformatics and Computational Genomics Laboratory, Princess Margaret Cancer Center, Toronto, ON, Canada
  114. 114. Department of Medicine, University of Melbourne, Parkville, VIC, Australia
  115. 115. Trev & Joyce Deeley Research Centre, British Columbia Cancer Agency, Victoria, BC, Canada
  116. 116. Providence Cancer Research Center, Portland, OR, United States
  117. 117. Department of Medical Oncology, Istituto Europeo di Oncologia, Milan, Italy
  118. 118. Department of Pathology, AZ Turnhout, Turnhout, Belgium
  119. 119. Department of Pathology, St Vincent’s University Hospital and University College Dublin, Dublin, Ireland
  120. 120. Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, United States
  121. 121. Azienda AUSL, Regional Hospital of Aosta, Aosta, Italy
  122. 122. Department of Clinical Medicine, Macquarie University, Sydney, NSW, Australia
  123. 123. HistoGeneX NV, Antwerp, Belgium and AZ Sint-Maarten Hospital, Mechelen, Belgium
  124. 124. Oncology Clinical Development, Bristol-Myers Squibb, Princeton, NJ, United States
  125. 125. Institut fur Pathologie, Hamburg, Germany, United Kingdom
  126. 126. Department of Medicine, Vanderbilt University Medical Centre, Nashville, TN, United States
  127. 127. Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, United States
  128. 128. Department of Oncology, Mayo Clinic, Rochester, MN, United States
  129. 129. Roche, Tucson, AZ, United States
  130. 130. Tumor Pathology Department, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland
  131. 131. Pathology and Tissue Analytics, Pharma Research and Early Development, Roche Innovation Center Munich, Penzberg, Germany
  132. 132. Sunnybrook Health Sciences Centre, Toronto, ON, Canada
  133. 133. Tehran University of Medical Sciences, Tehran, Iran
  134. 134. Oncology Biomarker Development, Genentech-Roche, San Francisco, CA, United States
  135. 135. Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
  136. 136. Department of Pathology, Hospital de Oncologia Maria Curie, Buenos Aires, Argentina
  137. 137. Directorate of Surgical Pathology, SA Pathology, Adelaide, Australia
  138. 138. Department of Pathology, University Hospital Antwerp, Edegem, Belgium
  139. 139. Translational Health Sciences, Department of Cellular Pathology, North Bristol NHS Trust, University of Bristol, Bristol, United Kingdom
  140. 140. Medical Oncology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States
  141. 141. Helsinki University Central Hospital, Helsinki, Finland
  142. 142. Department of Clinical Pathology, Akademiska University Hospital, Uppsala, Sweden
  143. 143. International Agency for Research on Cancer (IARC), World Health Organization, Lyon, France
  144. 144. Department of Pathology, Sanatorio Mater Dei, Buenos Aires, Argentina
  145. 145. Institute of Pathology, Medical University of Graz, Graz, Austria
  146. 146. Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
  147. 147. R&D UNICANCER, Paris, France
  148. 148. Precision Medicine, Oncology R&D, AstraZeneca, Gaithersberg, MD, United States
  149. 149. Breast Unit, Champalimaud Clinical Centre, Lisboa, Portugal
  150. 150. Department of Pathology, Massachusetts General Hospital, Boston, MA, United States
  151. 151. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, United States
  152. 152. Department of Oncology and Pathology, Karolinska Institutet and University Hospital, Solna, Sweden
  153. 153. Department of Medicine, Clinical Division of Oncology, Comprehensive Cancer Centre Vienna, Medical University of Vienna, Vienna, Austria
  154. 154. Leicester Cancer Research Centre, University of Leicester, Leicester, and MRC Toxicology Unit, University of Cambridge, Cambridge, United Kingdom
  155. 155. Merck & Co., Inc, Kenilworth, NJ, United States
  156. 156. GHI Le Raincy-Montfermeil, Chelles, Ile-de-France, Montfermeil, France
  157. 157. Department of Pathology, Gustave Roussy, Grand Paris, France
  158. 158. Departments of Medicine and Cancer Biology, Vanderbilt University Medical Centre, Nashville, TN, United States
  159. 159. Vm Scope, Berlin, Germany
  160. 160. Department of Pathology, Breast Pathology Section, Northwestern University, Chicago, IL, United States
  161. 161. Department of Biometrics, The Netherlands Cancer Institute, Amsterdam, Netherlands
  162. 162. Cancer Biomarkers Working Group, Faculty of Medicine and Pharmacy, Universite Mohamed Premier, Oujda, Morocco
  163. 163. Pathology Department, Stanford University Medical Centre, Stanford, CA, United States
  164. 164. Center for Pharmacogenomics and Fudan-Zhangjiang, Center for Clinical Genomics School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, China
  165. 165. GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre and Department of Pathology, Maastricht University Medical Centre, Maastricht, Netherlands
  166. 166. Biorepository and Tissue Technology Shared Resources, University of California San Diego, San Diego, CA, United States
  167. 167. Department of Pathology, Gustave Roussy, Villejuif, France
  168. 168. Departments of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
  169. 169. Hospital das Clinicas, Sao Paulo, Brasil
  170. 170. Department of Pathology, Faculty of Medicine, University of Sao Paulo, Sao Paulo, Brazil
  171. 171. Department of Medical Biology and Pathology, Gustave Roussy Cancer Campus, Villejuif, France
  172. 172. Department of Pathology, Academic Medical Center, Amsterdam, Netherlands
  173. 173. Institut Jules Bordet, Universite Libre de Bruxelles, Brussels, Belgium
  174. 174. Roche Tissue Diagnostics, Digital Pathology, Santa Clara, CA, United States
  175. 175. Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Centre, Nashville, TN, United States
  176. 176. Division of Biostatistics, Dana-Farber Cancer Institute, Boston, MA, United States
  177. 177. Roche Diagnostics Information Solutions, Belmont, CA, United States
  178. 178. Department of Anatomical Pathology, Royal Melbourne Hospital, Parkville, VIC, Australia
  179. 179. Vernon Cancer Center, Newton-Wellesley Hospital, Newton, MA, United States
  180. 180. Department of Pathology, Cliniques Universitaires Saint-Luc Bruxelles, Brussels, Belgium
  181. 181. Breast Center, Dept. OB&GYN and CCC (LMU), University of Munich, Munich, Germany
  182. 182. Division of Hematology-Oncology, Beth Israel Deaconess Medical Center, Boston, MA, United States
  183. 183. University of Leuven, Leuven, Belgium
  184. 184. Department of Pathology, Institut Jules Bordet, Universite Libre de Bruxelles, Brussels, Belgium
  185. 185. Department of Surgical Pathology and Biopathology, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France
  186. 186. Johanniter GmbH - Evangelisches Krankenhaus Bethesda Monchengladbach, West German Study Group, Monchengladbach, Germany
  187. 187. Molecular Oncology Group, Vall d’Hebron Institute of Oncology, Barcelona, Spain
  188. 188. Department of Pathology, University of Marburg, Marburg, Germany
  189. 189. Department of Histopathology, Manipal Hospitals Dwarka, New Delhi, India
  190. 190. Department of Anatomical Pathology, St Vincent’s Hospital Melbourne, Fitzroy, VIC, Australia
  191. 191. Cancer Immunotherapy Trials Network, Central Laboratory and Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
  192. 192. Clinical Trial Service Unit & Epidemiological Studies Unit, University of Oxford, Oxford, United Kingdom
  193. 193. Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Research Institute, Toronto, ON, Canada
  194. 194. The Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Australian Clinical Labs, Darlinghurst, NSW, Australia
  195. 195. Georgetown University Medical Center, Washington, DC, United States
  196. 196. Department of Molecular and Experimental Medicine, Avera Cancer Institute, Sioux Falls, SD, United States
  197. 197. Translational Medicine, Bristol-Myers Squibb, Princeton, NJ, United States
  198. 198. Department of Pathology, Ahfad University for Women, School of Medicine, Omdurman, Sudan
  199. 199. Guy’s Hospital, London, UK
  200. 200. King’s College London, London, United Kingdom
  201. 201. Department of Breast Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
  202. 202. Department of Health Sciences, University of Florence, Florence, Italy
  203. 203. Department of Oncology, Champalimaud Clinical Centre, Lisbon, Portugal
  204. 204. Department of Pathology, Fundacion Valle del Lili, Cali, Colombia
  205. 205. Department of Development and Regeneration, Laboratory of Experimental Urology, KU Leuven, Leuven, Belgium
  206. 206. Department of Medical Oncology, Austin Health, Heidelberg, VIC, Australia
  207. 207. Department of Surgery, Kansai Medical School, Hirakata, Japan
  208. 208. Pathology Department, H.U. Vall d’Hebron, Barcelona, Spain
  209. 209. Division of Bioinformatics and Biostatistics, U.S. Food and Drug Administration, Silver Spring, MD, United States
  210. 210. Department of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center, Providence, RI, United States
  211. 211. Universite Paris-Est, Creteil, France
  212. 212. Praava Health, Dhaka, Bangladesh
  213. 213. Department of Pathology, Medical University of Vienna, Vienna, Austria

Source: npj Breast Cancer Published:2020


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. © 2020, The Author(s).