Evidence map›Paper›PMID 25255793›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014

Multiplexed quantitative analysis of CD3, CD8, and CD20 predicts response to neoadjuvant chemotherapy in breast cancer.

Jason R Brown, Hallie Wimberly, Donald R Lannin, Christian Nixon, David L Rimm, Veerle Bossuyt

Open access · greenAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
115citing papers in PubMed, 1 pooled it
5.2field-weighted citation impact, top 3% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

115 citing papers in PubMed, 1 synthesis or guideline pooled it, 165 citations in OpenAlex.

  1. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014.Annals of oncology : official journal of the European Society for Medical Oncology · 2015
    Guideline
  2. Trial
  3. Multiplexed (18-Plex) Measurement of Signaling Targets and Cytotoxic T Cells in Trastuzumab-Treated Patients using Imaging Mass Cytometry.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019
    Trial
  4. Trial
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  6. Article
  7. Review
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  9. Article
  10. Article
  11. Spatial proximity of CD8NPJ breast cancer · 2025
    Article
  12. HER2-Positive Breast Cancer Treatment and Resistance.Advances in experimental medicine and biology · 2025
    Review
  13. Article
  14. Review
  15. Article
  16. Article
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  19. Article
  20. Article

55 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Jason R BrownDepartment of Pathology, Yale University Medical School, New Haven, Connecticut.
Hallie WimberlyDepartment of Pathology, Yale University Medical School, New Haven, Connecticut.
Donald R LanninDepartment of Surgery, Yale University Medical School, New Haven, Connecticut.
Christian NixonDepartment of Pathology, Yale University Medical School, New Haven, Connecticut.
David L RimmDepartment of Pathology, Yale University Medical School, New Haven, Connecticut. david.rimm@yale.edu.
Veerle BossuytDepartment of Pathology, Yale University Medical School, New Haven, Connecticut.
Yale University · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9M
Predicting Metastasis in MelanomaR01CA114277 · NCI · YALE UNIVERSITY · PI RIMM, DAVID L · 2006 to 2013
$2.1M
Estrogen Receptor Alpha Proteostasis in Breast CancerR01CA159578 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI ALARID, ELAINE T · 2011 to 2015
$1.5M
NCI NIH HHS R-01 CA 114277NCI NIH HHS R01 CA114277NCI NIH HHS R01 CA159578NIGMS NIH HHS T32 GM007205NIGMS NIH HHS TG T32GM07205
6 · The paper itself

Abstract

purposeAlthough tumor-infiltrating lymphocytes (TIL) have been associated with response to neoadjuvant therapy, measurement typically is subjective, semiquantitative, and unable to differentiate among subpopulations. Here, we describe a quantitative objective method for analyzing lymphocyte subpopulations and assessing their predictive value. EXPERIMENTAL

designWe developed a quantitative immunofluorescence assay to measure stromal expression of CD3, CD8, and CD20 on one slide. We validated this assay by comparison with flow cytometry on tonsil specimens and assessed predictive value in breast cancer on a neoadjuvant cohort (n = 95). Then, each marker was tested for prediction of pathologic complete response (pCR) compared with pathologist estimation of the percentage of lymphocyte infiltrate.

resultsThe lymphocyte percentage and CD3, CD8, and CD20 proportions were similar between flow cytometry and quantitative immunofluorescence on tonsil specimens. Pathologist TIL count predicted pCR [P = 0.043; OR, 4.77; 95% confidence interval (CI), 1.05-21.6] despite fair interobserver reproducibility (κ = 0.393). Stromal AQUA (automated quantitative analysis) scores for CD3 (P = 0.023; OR, 2.51; 95% CI, 1.13-5.57), CD8 (P = 0.029; OR, 2.00; 95% CI, 1.08-3.72), and CD20 (P = 0.005; OR, 1.80; 95% CI, 1.19-2.72) predicted pCR in univariate analysis. CD20 AQUA score predicted pCR (P = 0.019; OR, 5.37; 95% CI, 1.32-21.8) independently of age, size, nuclear grade, nodal status, ER, PR, HER2, and Ki-67, whereas CD3, CD8, and pathologist estimation did not.

conclusionsWe have developed and validated an objective, quantitative assay measuring TILs in breast cancer. Although this work provides analytic validity, future larger studies will be required to prove clinical utility.

Indexed as

AdultAgedAntigens, CD20Antineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsCD3 ComplexCD8 AntigensChemotherapy, AdjuvantFemaleHumansImmunophenotypingLymphocytes, Tumor-InfiltratingLymphocyte SubsetsMiddle AgedNeoadjuvant TherapyAntigens, CD20Biomarkers, TumorCD3 ComplexCD8 Antigens

Identifiers

PMID25255793
PMCPMC4252785
OpenAlexW2104453868

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.