Evidence map›Paper›PMID 25071121›Full record

ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2014

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 and 6 more

Registry-linked trialOpen access · bronzeAbstract readValidation Study
In one paragraph

Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04368468 (Study of the Modifications of the Immune Microenvironment Induced by Neoadjuvant Chemotherapy in Triple-negative Breast Cancers), which is not on this map. Cited by 735 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
735citing papers in PubMed, 3 pooled it
51.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04368468 completednot on this mapstarted 2020, after this paper: background citation

Study of the Modifications of the Immune Microenvironment Induced by Neoadjuvant Chemotherapy in Triple-negative Breast Cancers

TypeobservationalSponsorInstitut Claudius RegaudRan2020 to 2021Enrolled100ConditionsTriple Negative Breast CancerArmsbiomarker evolution
3 · Its place in the literature

Who cites it

735 citing papers in PubMed, 3 syntheses or guidelines pooled it, 1,327 citations in OpenAlex.

  1. Pooled it
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  14. Multi-omic Profiling of Recurrence Risk Across Breast Cancer Subtypes.medRxiv : the preprint server for health sciences · 2026
    Article
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675 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 1 institution in 1 country.

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
Indiana University – Purdue University Indianapolis · US

Funding

Project-006U10CA180820 · NCI · ECOG-ACRIN MEDICAL RESEARCH FOUNDATION · PI Peter J ODwyer · 2014 to 2026
$167.6M
CANCER AND LEUKEMIA GROUP B MINORITY SATELLITE SUPPLEMENU10CA031946 · NCI · UNIVERSITY OF CHICAGO · PI BERTAGNOLLI, MONICA M · 1985 to 2013
$158.4M
SWOG Network Group Operations Center of the NCTNU10CA180888 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI PRIMO N. LARA · 2014 to 2026
$152.1M
Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI AKHILESH PANDEY · 1985 to 2026
$151.3M
SWOG - Foreign Accrual under UMiU10CA032102 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BLANKE, CHARLES D. · 1985 to 2013
$141.3M
ECOG OPERATIONS OFFICE (IBCSG)U10CA021115 · NCI · UNIVERSITY OF WISCONSIN MADISON · PI COMIS, ROBERT L · 1985 to 2013
$132.6M
WORD PROCESSORP30CA013330 · NCI · YESHIVA UNIVERSITY · PI STEVEN C. ALMO · 1985 to 2026
$111.2M
Statistics CoreU10CA180794 · NCI · DANA-FARBER CANCER INST · PI PAUL J CATALANO · 2014 to 2026
$111.2M
TRANSLATIONAL RESEARCHU10CA025224 · NCI · MAYO CLINIC ROCHESTER · PI BUCKNER, JAN C · 1985 to 2013
$85.0M
ECOG Statistical Office Data Management GrantU10CA066636 · NCI · FRONTIER SCI &TECHNOLOGY RSCH FDN, INC · PI GRAY, ROBERT J · 1994 to 2013
$39.5M
PROVIDE STATISTICAL SERVICESU10CA023318 · NCI · DANA-FARBER CANCER INSTITUTE · PI GRAY, ROBERT J · 1985 to 2013
$33.4M
ECOG Specimen BankingU24CA114737 · NCI · FRONTIER SCI &TECHNOLOGY RSCH FDN, INC · PI COMIS, ROBERT L · 2005 to 2014
$9.3M
NCI NIH HHS CA114737NCI NIH HHS CA11789NCI NIH HHS CA14958NCI NIH HHS CA16116NCI NIH HHS CA21076NCI NIH HHS CA21115NCI NIH HHS CA23318NCI NIH HHS CA25224NCI NIH HHS CA27525NCI NIH HHS CA31946NCI NIH HHS CA39229NCI NIH HHS CA49883NCI NIH HHS CA66636NCI NIH HHS N01 CA032102NCI NIH HHS P30 CA013330NCI NIH HHS P30 CA015083NCI NIH HHS R01 CA161891NCI NIH HHS R01CA161891NCI NIH HHS U10 CA014958NCI NIH HHS U10 CA016116NCI NIH HHS U10 CA021076NCI NIH HHS U10 CA021115NCI NIH HHS U10 CA023318NCI NIH HHS U10 CA025224NCI NIH HHS U10 CA027525NCI NIH HHS U10 CA031946NCI NIH HHS U10 CA032102NCI NIH HHS U10 CA039229NCI NIH HHS U10 CA049883NCI NIH HHS U10 CA066636NCI NIH HHS U10 CA180794NCI NIH HHS U10 CA180795NCI NIH HHS U10 CA180802NCI NIH HHS U10 CA180820NCI NIH HHS U10 CA180888NCI NIH HHS U24 CA114737NCI NIH HHS UG1 CA233196
6 · The paper itself

Abstract

purposeRecent 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

methodsFull-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.

resultsThe 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.

conclusionIn 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.

Indexed as

Lymphocytes, Tumor-InfiltratingAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorChemotherapy, AdjuvantClinical Trials, Phase III as TopicDisease-Free SurvivalFemaleHumansKaplan-Meier EstimateMiddle AgedPredictive Value of TestsPrognosisRandomized Controlled Trials as TopicBiomarkers, Tumor

Identifiers

PMID25071121
PMCPMC4162494
OpenAlexW2098683355

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.