Evidence map›Paper›PMID 30868392›Full record

ArticleBreast cancer research and treatment2019

Strong CD8+ lymphocyte infiltration in combination with expression of HLA class I is associated with better tumor control in breast cancer patients treated with neoadjuvant chemotherapy.

A F de Groot, E J Blok, A Charehbili, C C Engels, V T H B M Smit, N G Dekker-Ensink, H Putter, E Meershoek-Klein Kranenbarg, C J H van de Velde, G J Liefers and 4 more

Abstract read
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In one paragraph

Article in Breast cancer research and treatment, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 3 pooled it
–field-weighted citation impact
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

11 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. The prognostic values of FOXP3Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
    Pooled it
  4. The immunology of human breast cancer.Nature reviews. Immunology · 2026
    Review
  5. Article
  6. New insights on anti-tumor immunity of CD8Journal of translational medicine · 2025
    Review
  7. Review
  8. Article
  9. Prognostic value of CD8Oncology letters · 2023
    Article
  10. Article
  11. Review
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

14 authors.

A F de GrootDepartment of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
E J BlokDepartment of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
A CharehbiliDepartment of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
C C EngelsDepartment of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
V T H B M SmitDepartment of Pathology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
N G Dekker-EnsinkDepartment of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
H PutterDepartment of Statistics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
E Meershoek-Klein KranenbargDepartment of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
C J H van de VeldeDepartment of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
G J LiefersDepartment of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
J W R NortierDepartment of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
P J K KuppenDepartment of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
S H van der BurgDepartment of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
J R KroepDepartment of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. j.r.kroep@lumc.nl.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeTumor-infiltrating lymphocytes (TILs) are associated with pathological complete response (pCR) and survival after neoadjuvant chemotherapy (NAC) in patients with early breast cancer. We investigated the prognostic and predictive role of TILs, macrophages, and HLA class 1 expression after NAC with or without the potentially immune modulating compound zoledronic acid (ZA).

methodsBaseline tumor biopsies from 196 patients in the NEOZOTAC trial were analyzed for CD8 (cytotoxic T-cells), FoxP3 (regulatory T-cells), CD68 (macrophages), and HLA class I (HCA2/HC10) expression by immunohistochemistry and subsequently related to pCR and disease-free survival (DFS).

resultsA strong intratumoral CD8+ infiltration or expression of HLA class 1 by cancer cells was associated with a higher pCR rate (p < 0.05). Clinical benefit of high CD8+ T-cell infiltration was found when cancer cells expressed HLA class 1 (pCR: 21.8% vs. 6.7%, p = 0.04) but not when HLA class 1 expression was lost or downregulated (pCR: 5.9% vs. 0%, p = 0.38). Interaction analyses revealed survival benefit between HLA class 1 expression and strong CD8+ T-cell infiltration, whereas in the absence or downregulation of HLA class 1 expression, high levels of CD8+ T-cells were associated with survival disadvantage (p for interaction 0.01; hazard ratio 0.41, 95% CI 0.15-1.10, p = 0.08 and hazard ratio 7.67, 95% CI 0.88-66.4, p = 0.07, respectively). Baseline immune markers were not related to ZA treatment.

conclusionsStrong baseline tumor infiltration with CD8+ T-cells in the presence of tumoral HLA class 1 expression in patients with HER2-negative breast cancer is related to a higher pCR rate and a better DFS after NAC.

Indexed as

AgedBreast NeoplasmsCD8-Positive T-LymphocytesClinical Trials, Phase III as TopicDisease-Free SurvivalDrug TherapyFemaleHistocompatibility Antigens Class IHumansLymphocytes, Tumor-InfiltratingMiddle AgedNeoadjuvant TherapyPrognosisRandomized Controlled Trials as TopicSurvival AnalysisTreatment OutcomeHistocompatibility Antigens Class IZoledronic AcidBreast cancerHLA class 1Neoadjuvant chemotherapyPathological complete responseTumor-infiltrating lymphocytesZoledronic acid

Identifiers

PMID30868392
PMCPMC6534526

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Registered trials

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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.