title: Clinical validity of tumor-infiltrating lymphocytes analysis in patients with triple-negative breast cancer.
abstract: BACKGROUND
  Although tumor-infiltrating lymphocytes (TILs) have been associated with a favorable prognosis in triple-negative breast cancer (TNBC) patients, this marker is not currently considered robust enough for entering the clinical practice. In the present study, we assessed the clinical validity of the guidelines recently issued by the International TIL Working Group in a large retrospective series of well-annotated TNBC patients.
  
  
  METHODS
  TILs were evaluated in all the full-face H&E sections from 897 consecutive TNBC (i.e. tumors with <1% of ER and PgR immunoreactivity and absence of HER2 overexpression or amplification) patients diagnosed and treated at the European Institute of Oncology between 1995 and 2010 (median follow-up 8.2 years, range 6 months to 18 years). All mononuclear cells were evaluated in the stromal area within the borders of the invasive tumor, reported as a percentage value and treated as a continuous variable in survival analysis.
  
  
  RESULTS
  The median percentage of TILs was 20%, and 21.9% of the cases had ≥50% (lymphocyte predominant breast cancer, LPBC) TILs. At univariable survival analysis, TILs were a significant predictor of better disease-free survival (DFS), distant disease-free survival (DDFS) and overall survival (OS) (P < 0.0001). Multivariable analysis confirmed that each 10% increase in TILs strongly predicted better survival, independent of patients' age, lymph node status, tumor size, histological grade, peritumoral vascular invasion and Ki-67 labeling index. Patients with LPBC had a 10-year survival rate of 71%, 84% and 96% for DFS, DDFS and OS, respectively. Stratified analysis revealed a positive correlation between TILs and OS across all the subgroups analyzed.
  
  
  CONCLUSIONS
  Our data support the analytical validity of the recently issued TILs evaluation guidelines in the clinical practice.
authors.affiliation: Department of Pathology, Biobank for Translational Medicine Unit University of Milan, School of Medicine, Milan giancarlo.pruneri@ieo.it.
authors.forename: G
authors.initials: G
authors.lastname: Pruneri
authors.affiliation: Division of Pathology University of Milan, School of Medicine, Milan.
authors.forename: A
authors.initials: A
authors.lastname: Vingiani
authors.affiliation: Division of Epidemiology and Biostatistics Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Bagnardi
authors.affiliation: Division of Epidemiology and Biostatistics.
authors.forename: N
authors.initials: N
authors.lastname: Rotmensz
authors.affiliation: Division of Pathology.
authors.forename: A
authors.initials: A
authors.lastname: De Rose
authors.affiliation: Division of Medical Senology.
authors.forename: A
authors.initials: A
authors.lastname: Palazzo
authors.affiliation: Division of Medical Senology.
authors.forename: A M
authors.initials: AM
authors.lastname: Colleoni
authors.affiliation: Division of Program of Breast Health (Senology), European Institute of Oncology, Milan International Breast Cancer Study Group, Bern, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Goldhirsch
authors.affiliation: Division of Pathology University of Milan, School of Medicine, Milan.
authors.forename: G
authors.initials: G
authors.lastname: Viale
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000276:immunology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008875:Middle Aged; D012189:Retrospective Studies; D064726:Triple Negative Breast Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology* / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
keywords: breast; cancer; chemotherapy; survival; triple negative; tumor-infiltrating lymphocytes