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Adams S , Gray RJ , Demaria S , Goldstein L , Perez EA , Shulman LN , Martino S , Wang M , Jones VE , Saphner TJ , Wolff AC , Wood WC , Davidson NE , Sledge GW , Sparano JA , Badve SS
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
J Clin Oncol. 2014 Sep 20;32(27) :2959-66
PMID: 25071121    PMCID: PMC4162494    URL: https://www.ncbi.nlm.nih.gov/pubmed/25071121
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PURPOSE: 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). PATIENTS AND 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. CONCLUSION: 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.
Adams, Sylvia Gray, Robert J Demaria, Sandra Goldstein, Lori Perez, Edith A Shulman, Lawrence N Martino, Silvana Wang, Molin Jones, Vicky E Saphner, Thomas J Wolff, Antonio C Wood, William C Davidson, Nancy E Sledge, George W Sparano, Joseph A Badve, Sunil S eng CA21076/CA/NCI NIH HHS/ CA114737/CA/NCI NIH HHS/ U10 CA027525/CA/NCI NIH HHS/ R01CA161891/CA/NCI NIH HHS/ CA11789/CA/NCI NIH HHS/ CA14958/CA/NCI NIH HHS/ R01 CA161891/CA/NCI NIH HHS/ N01 CA032102/CA/NCI NIH HHS/ U10 CA180802/CA/NCI NIH HHS/ U10 CA014958/CA/NCI NIH HHS/ CA66636/CA/NCI NIH HHS/ U10 CA021115/CA/NCI NIH HHS/ U10 CA031946/CA/NCI NIH HHS/ CA27525/CA/NCI NIH HHS/ U10 CA049883/CA/NCI NIH HHS/ U10 CA021076/CA/NCI NIH HHS/ U10 CA180795/CA/NCI NIH HHS/ U10 CA066636/CA/NCI NIH HHS/ U10 CA039229/CA/NCI NIH HHS/ CA39229/CA/NCI NIH HHS/ U10 CA032102/CA/NCI NIH HHS/ P30 CA015083/CA/NCI NIH HHS/ U10 CA016116/CA/NCI NIH HHS/ U10 CA180820/CA/NCI NIH HHS/ CA25224/CA/NCI NIH HHS/ U10 CA023318/CA/NCI NIH HHS/ U10 CA180794/CA/NCI NIH HHS/ P30 CA013330/CA/NCI NIH HHS/ CA49883/CA/NCI NIH HHS/ CA21115/CA/NCI NIH HHS/ U10 CA025224/CA/NCI NIH HHS/ U24 CA114737/CA/NCI NIH HHS/ U10 CA180888/CA/NCI NIH HHS/ CA23318/CA/NCI NIH HHS/ CA31946/CA/NCI NIH HHS/ CA16116/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Validation Study J Clin Oncol. 2014 Sep 20;32(27):2959-66. doi: 10.1200/JCO.2013.55.0491.