title: 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.
abstract: OBJECTIVE
  Recent studies suggest that tumor-infiltrating lymphocytes (TILs) are associated with disease-free (DFS) and overall survival (OS) in operable triple-negative breast cancer (TNBC). We seek to validate the prognostic impact of TILs in primary TNBCs in two adjuvant phase III trials conducted by the Eastern Cooperative Oncology Group (ECOG).
  
  
  METHODS
  Full-face hematoxylin and eosin–stained sections of 506 tumors from ECOG trials E2197 and E1199 were evaluated for density of TILs in intraepithelial (iTILs) and stromal compartments (sTILs). Patient cases of TNBC from E2197 and E1199 were randomly selected based on availability of sections. For the primary end point of DFS, association with TIL scores was determined by fitting proportional hazards models stratified on study. Secondary end points were OS and distant recurrence–free interval (DRFI). Reporting recommendations for tumor marker prognostic studies criteria were followed, and all analyses were prespecified.
  
  
  RESULTS
  The majority of 481 evaluable cancers had TILs (sTILs, 80%; iTILs, 15%). With a median follow-up of 10.6 years, higher sTIL scores were associated with better prognosis; for every 10% increase in sTILs, a 14% reduction of risk of recurrence or death (P = .02), 18% reduction of risk of distant recurrence (P = .04), and 19% reduction of risk of death (P = .01) were observed. Multivariable analysis confirmed sTILs to be an independent prognostic marker of DFS, DRFI, and OS.
  
  
  CONCLUSIONS
  In two national randomized clinical trials using contemporary adjuvant chemotherapy, we confirm that stromal lymphocytic infiltration constitutes a robust prognostic factor in TNBCs. Studies assessing outcomes and therapeutic efficacies should consider stratification for this parameter.
authors: Sylvia
authors: S
authors: Adams
authors: Robert J
authors: RJ
authors: Gray
authors: Sandra
authors: S
authors: Demaria
authors: Lori
authors: L
authors: Goldstein
authors: Edith A
authors: EA
authors: Perez
authors: Lawrence N
authors: LN
authors: Shulman
authors: Silvana
authors: S
authors: Martino
authors: Molin
authors: M
authors: Wang
authors: Vicky E
authors: VE
authors: Jones
authors: Thomas J
authors: TJ
authors: Saphner
authors: Antonio C
authors: AC
authors: Wolff
authors: William C
authors: WC
authors: Wood
authors: Nancy E
authors: NE
authors: Davidson
authors: George W
authors: GW
authors: Sledge
authors: Joseph A
authors: JA
authors: Sparano
authors: Sunil S
authors: SS
authors: Badve
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D017024:Chemotherapy, Adjuvant; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results; D012189:Retrospective Studies; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor