Evidence map›Paper›PMID 40140821›Full record

Trial reportMolecular cancer2025

Immunomodulatory gene networks predict treatment response and survival to de-escalated, anthracycline-free neoadjuvant chemotherapy in triple-negative breast cancer in the WSG-ADAPT-TN trial.

Darren Korbie, Clare Stirzaker, Oleg Gluz, Christine Zu Eulenburg, Ulrike Nitz, Matthias Christgen, Sherko Kuemmel, Eva-Maria Grischke, Helmut Forstbauer, Michael Braun and 12 more

Registry-linked trialAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Molecular cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01815242 (Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer - Triple Negative Breast Cancer), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–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.

NCT01815242 phase2completednot on this map

Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer - Triple Negative Breast Cancer

TypeinterventionalSponsorWomen's Cancer Study Group GmbHRan2013 to 2025Enrolled336ConditionsBreast CancerArmsnab-Paclitaxel, Gemcitabine, Carboplatin
3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Article
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

22 authors.

Darren Korbie *Centre for Personalised Nanomedicine, The University of Queensland, St Lucia, 4072, QLD, Australia.
Clare Stirzaker *Epigenetics Research Laboratory, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia.
Oleg GluzWest German Study Group, Moenchengladbach, Germany.
Christine Zu EulenburgWest German Study Group, Moenchengladbach, Germany.
Ulrike NitzWest German Study Group, Moenchengladbach, Germany.
Matthias ChristgenInstitute of Pathology, Hannover Medical School, Hannover, Germany.
Sherko KuemmelWest German Study Group, Moenchengladbach, Germany.
Eva-Maria GrischkeWomen's Clinic, University Clinics Tuebingen, Tuebingen, Germany.
Helmut ForstbauerPractice Network Troisdorf, Troisdorf, Germany.
Michael BraunBreast Center, Rotkreuz Clinics Munich, Munich, Germany.
Mathias WarmBreast Center, City Hospital Holweide, Cologne, Germany.
John HackmannBreast Center, Marien-Hospital, Witten, Germany.
Christoph UleerPractice of Gynecology and Oncology, Hildesheim, Germany.
Bahriye AktasWomen's Clinic, University Clinics Essen, Essen, Germany.
Claudia SchumacherBreast Center, St. Elisabeth Hospital, Cologne, Germany.
Rachel WuerstleinWest German Study Group, Moenchengladbach, Germany.
Enrico PelzInstitute for Pathology, Viersen, Germany.
Hans Heinrich KreipeInstitute of Pathology, Hannover Medical School, Hannover, Germany.
Susan J ClarkEpigenetics Research Laboratory, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia.
Matt TrauCentre for Personalised Nanomedicine, The University of Queensland, St Lucia, 4072, QLD, Australia.
Monika Graeser *West German Study Group, Moenchengladbach, Germany. monika.graeser@wsg-online.com.
Nadia Harbeck *West German Study Group, Moenchengladbach, Germany.

Funding

National Breast Cancer Foundation CG-12-07National Health and Medical Research Council #1156408
6 · The paper itself

Abstract

backgroundAnthracycline-containing neoadjuvant chemotherapy (NACT) is the standard treatment for early triple-negative breast cancer (eTNBC); however, it is associated with substantial toxicity. We performed whole transcriptome profiling of baseline tumor biopsies to identify gene networks predictive and prognostic for pathological complete response (pCR) and survival after de-escalated, anthracycline-free NACT in the WSG-ADAPT-TN trial (NCT01815242).

methodseTNBC patients (cT1c-cT4c, cN +) were randomized to 12 weeks of nab-paclitaxel + gemcitabine (n = 182) or nab-paclitaxel + carboplatin (n = 154). The primary endpoint was pCR (ypT0/is, ypN0), and the secondary endpoints included survival and translational research. AmpliSeq RNA sequencing, allowing simultaneous analysis of the expression of > 20,000 genes, was performed in 135 patients. Differentially expressed genes were evaluated in training (n = 67) and validation (n = 68) sets, and a polygenic score (PS) for prediction of pCR (PS:pCR) and a PS for prediction of invasive disease-free survival (PS:iDFS) were found.

results49/135 (36.3%) patients had pCR; 30 iDFS events occurred during 60-month median follow-up. Immune recruitment and viral defense gene networks were strongly associated with pCR, while metabolic pathways were associated with survival. PS:pCR and PS:iDFS predominantly included immune-related genes. Diagnostic accuracy (ROC AUC) in the validation cohort was 83% for PS:pCR and 64% for PS:iDFS. At optimized cut-off, PS:pCR identified a group with a 67.7% pCR rate (vs. 10.8%; p < .0001), and PS:iDFS detected a group with 79.5% (95%CI 64.1%, 88.8%) 5-year iDFS rate (vs. 55.0%, 95%CI 29.8%, 74.5%; p = .04).

conclusionPolygenic scores incorporating immunoregulatory genes can predict pCR and survival and represent an opportunity to select patients for de-escalated, anthracycline-free NACT. This transcriptome network analysis also identifies potential new targets for personalized medicine approaches in patients without response to NACT.

trial registrationNCT01815242.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorGene Regulatory NetworksImmunomodulationTriple Negative Breast NeoplasmsAdultAgedAnthracyclinesFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMiddle AgedNeoadjuvant TherapyPaclitaxelPrognosisAnthracyclinesBiomarkers, TumorPaclitaxelBiomedicalGene expression profilingGene regulatory networksNeoadjuvant therapyPrognosisTranslational researchTriple negative breast neoplasms

Identifiers

PMID40140821
PMCPMC11938552

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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.