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 - PubMed (original) (raw)
. 2014 Sep 20;32(27):2959-66.
doi: 10.1200/JCO.2013.55.0491.
Robert J Gray, Sandra Demaria, Lori Goldstein, Edith A Perez, Lawrence N Shulman, Silvana Martino, Molin Wang, Vicky E Jones, Thomas J Saphner, Antonio C Wolff, William C Wood, Nancy E Davidson, George W Sledge, Joseph A Sparano, Sunil S Badve
- PMID: 25071121
- PMCID: PMC4162494
- DOI: 10.1200/JCO.2013.55.0491
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
Sylvia Adams et al. J Clin Oncol. 2014.
Abstract
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.
Conflict of interest statement
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
Figures
Fig 1.
Variable degree of lymphocytic infiltrate in triple-negative breast cancer on hematoxylin and eosin (HE) –stained tumor sections. Examples of tumors without intraepithelial tumor-infiltrating lymphocytes (TILs) but varying degrees of stromal TILs by HE: (A) 0%, (B) 20%, (C) formation of germinal follicles, and (D) 80% (×10 magnification). (E) Representative example of lymphocyte-predominant breast cancer (×5 magnification) with 10% intraepithelial TILs (inset, black arrow, lymphocytes in direct contact with cancer cells) and 80% stromal TILs (inset, red arrow, abundant lymphocytes within stroma).
Fig 2.
Prognostic value of tumor-infiltrating lymphocytes (TILs) in triple-negative breast cancer. Kaplan-Meier curves of estimated disease-free survival (DFS) for all patients for (A) stromal TIL (sTIL) score and (B) intraepithelial TIL (iTIL) score (grouped as 0 [defined as 0% to 1%] v 10 [2% to 10%] v 20 to 40 [11% to 40%] v 50 [41% to 50%] or v 50 to 80 [41% to 80%]); P values are for comparison of four groups.
Fig 3.
Prognostic value of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative breast cancer. Kaplan-Meier curves of estimated (A) distant recurrence–free interval (DRFI) and (B) overall survival (OS) for all patients for sTILs (grouped as 0 [defined as 0% to 1%] v 10 [2% to 10%] v 20 to 40 [11% to 40%] v 50 to 80 [41% to 80%]); P values are for comparison of four groups.
Fig A1.
Flow diagram of breast cancer specimens used from E2197 and E1199. To reach sample size of 500, as required by prespecified power analysis, samples were needed from second trial in addition to well-characterized cohort from E2197. ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; PR, progesterone receptor; TNBC, triple-negative breast cancer.
Comment in
- Host antitumor immunity plays a role in the survival of patients with newly diagnosed triple-negative breast cancer.
Loi S. Loi S. J Clin Oncol. 2014 Sep 20;32(27):2935-7. doi: 10.1200/JCO.2014.56.7677. J Clin Oncol. 2014. PMID: 25071115 No abstract available. - Tumor-infiltrating lymphocytes in breast cancer: ready for prime time?
Ocaña A, Diez-Gónzález L, Adrover E, Fernández-Aramburo A, Pandiella A, Amir E. Ocaña A, et al. J Clin Oncol. 2015 Apr 10;33(11):1298-9. doi: 10.1200/JCO.2014.59.7286. Epub 2015 Mar 9. J Clin Oncol. 2015. PMID: 25753437 No abstract available. - Tumor-infiltrating lymphocytes in triple-negative breast cancer: a biomarker for use beyond prognosis?
Tsoutsou PG, Bourhis J, Coukos G. Tsoutsou PG, et al. J Clin Oncol. 2015 Apr 10;33(11):1297-8. doi: 10.1200/JCO.2014.59.2808. Epub 2015 Mar 9. J Clin Oncol. 2015. PMID: 25753438 No abstract available.
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