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, 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

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Abstract

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.

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).

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.

Original languageEnglish (US)
Pages (from-to)2959-2966
Number of pages8
JournalJournal of Clinical Oncology
Volume32
Issue number27
DOIs
StatePublished - Sep 20 2014

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Triple Negative Breast Neoplasms
Tumor-Infiltrating Lymphocytes
Breast Neoplasms
Risk Reduction Behavior
Recurrence
Survival
Hematoxylin
Adjuvant Chemotherapy
Eosine Yellowish-(YS)
Tumor Biomarkers
Proportional Hazards Models
Neoplasms
Randomized Controlled Trials
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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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. / 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.

In: Journal of Clinical Oncology, Vol. 32, No. 27, 20.09.2014, p. 2959-2966.

Research output: Contribution to journalArticle

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 2014, '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', Journal of Clinical Oncology, vol. 32, no. 27, pp. 2959-2966. https://doi.org/10.1200/JCO.2013.55.0491
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. / 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. In: Journal of Clinical Oncology. 2014 ; Vol. 32, No. 27. pp. 2959-2966.
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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 = "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.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).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.",
author = "Sylvia Adams and Gray, {Robert J.} and Sandra Demaria and Lori Goldstein and Perez, {Edith A.} and Shulman, {Lawrence N.} and Silvana Martino and Molin Wang and Jones, {Vicky E.} and Saphner, {Thomas J.} and Wolff, {Antonio C.} and Wood, {William C.} and Davidson, {Nancy E.} and Sledge, {George W.} and Sparano, {Joseph A.} and Badve, {Sunil S.}",
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T1 - Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials

T2 - ECOG 2197 and ECOG 1199

AU - Adams, Sylvia

AU - Gray, Robert J.

AU - Demaria, Sandra

AU - Goldstein, Lori

AU - Perez, Edith A.

AU - Shulman, Lawrence N.

AU - Martino, Silvana

AU - Wang, Molin

AU - Jones, Vicky E.

AU - Saphner, Thomas J.

AU - Wolff, Antonio C.

AU - Wood, William C.

AU - Davidson, Nancy E.

AU - Sledge, George W.

AU - Sparano, Joseph A.

AU - Badve, Sunil S.

PY - 2014/9/20

Y1 - 2014/9/20

N2 - 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.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).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.

AB - 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.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).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.

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