title: Predictive and Prognostic Role of Tumor-Infiltrating Lymphocytes for Early Breast Cancer According to Disease Subtypes: Sensitivity Analysis of Randomized Trials in Adjuvant and Neoadjuvant Setting.
abstract: BACKGROUND
  The role of tumor-infiltrating lymphocytes (TILs) in breast cancer (BC) is still an issue for clinical research. Toward this end, a sensitivity analysis of neoadjuvant and adjuvant randomized clinical trials was performed according to disease subtypes.
  
  
  METHODS
  Pathological complete responses (pCRs) after neoadjuvant treatment according to the presence or absence of lymphocyte-predominant BC (LPBC) were extracted and cumulated as odds ratios (ORs) by adopting a random-effects model by subtype. Overall survival hazard ratios as a function of 10% incremental values of stromal TILs (sTILs) in adjuvant trials were extracted. The interaction test was adopted to determine the differential effect according to the subtype.
  
  
  RESULTS
  Eight trials (5,514 patients) were identified. With regard to neoadjuvant setting (4 studies), a significant interaction (p < .0001) according to LPBC was found. The presence of LPBC was associated with a 29.5% increase in pCR rate compared with non-LPBC (p < .0001). The pCR rate was significantly higher in patients with LPBC in triple-negative BC (TNBC) and HER2-positive BC settings, with an absolute difference of 15.7% (95% confidence interval [CI], 4.9%-26.2%) and 33.3% (95% CI, 23.6%-42.7%), respectively. With respect to the adjuvant setting (4 studies), a significant interaction (p < .0001) according to sTILs was found. A survival benefit was more likely to be determined for HER2-positive BC (p = .025) and TNBC (p < .0001), with no statistically significant difference for estrogen receptor-positive/HER2-negative disease.
  
  
  CONCLUSIONS
  Despite the retrospective nature of this analysis, the presence of TILs may represent a robust predictive and prognostic marker for BC, particularly for TNBC and HER2-positive disease.
authors: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
authors: Luisa
authors: L
authors: Carbognin
authors: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
authors: Sara
authors: S
authors: Pilotto
authors: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
authors: Rolando
authors: R
authors: Nortilli
authors: Department of Pathology and Diagnostics, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
authors: Matteo
authors: M
authors: Brunelli
authors: Department of Pathology and Diagnostics, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
authors: Alessia
authors: A
authors: Nottegar
authors: Biostatistics, Regina Elena National Cancer Institute, Roma, Italy.
authors: Isabella
authors: I
authors: Sperduti
authors: Biostatistics, Regina Elena National Cancer Institute, Roma, Italy.
authors: Diana
authors: D
authors: Giannarelli
authors: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy emilio.bria@univr.it.
authors: Emilio
authors: E
authors: Bria
authors: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
authors: Giampaolo
authors: G
authors: Tortora
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000276:immunology*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D020360:Neoadjuvant Therapy; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor
keywords: Adjuvant; Breast cancer; Neoadjuvant; Prognosis; Sensitivity analysis; Tumor-infiltrating lymphocytes