Evidence mapPaperPMID 41645311Full record

ArticleBreast cancer research : BCR2026

Tumor heterogeneity index from DCE-MRI for AKT-inhibition responder identification and reveals hot immune microenvironment for patients with breast cancer: a multi-omics analysis of I-SPY2 trial.

Xinzhi Teng, Jiang Zhang, Qingpei Lai, Wen Li, Xinyu Fan, Xinyu Zhang, Yu-Hua Huang, Jiahuan Wang, Chenyang Liu, Ge Ren and 6 more

Abstract read
In one paragraph

Article in Breast cancer research : BCR, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

16 authors.

Xinzhi Teng *Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
Jiang Zhang *Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
Qingpei Lai *Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
Wen LiDepartment of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.
Xinyu FanDepartment of Applied Mathematics, The Hong Kong Polytechnic University, Hong Kong, China.
Xinyu ZhangDepartment of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
Yu-Hua HuangDepartment of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
Jiahuan WangDepartment of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
Chenyang LiuDepartment of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
Ge RenDepartment of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
Habib ZaidiDivision of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, Geneva, Switzerland.
Elaine Yuen Phin LeeDepartment of Diagnostic Radiology, Queen Mary Hospital, The University of Hong Kong, Pok Fu Lam, Hong Kong, China.
Aya El HelaliLKS Faculty of Medicine, Department of Clinical Oncology, School of Clinical Medicine, The University of Hong Kong, Pok Fu Lam, China.
Lina ZhaoDepartment of Radiotherapy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Defeng SunDepartment of Applied Mathematics, The Hong Kong Polytechnic University, Hong Kong, China.
Jing CaiDepartment of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China. jing.cai@polyu.edu.hk.

Funding

Health Bureau HMRF 09200576Hong Kong Polytechnic University P0035421Innovation and Technology Commission MHP/005/20Shenzhen Science and Technology Innovation Program JCYJ20210324130209023
6 · The paper itself

Abstract

backgroundThe pan-AKT inhibitor MK2206 has shown improved but limited efficacy in achieving pathologic complete response (pCR) in patients with breast cancer receiving standard neoadjuvant chemotherapy (NACT). This study aimed to develop non-invasive tumor heterogeneity index (THI) from dynamic-contrast-enhanced magnetic resonance imaging (DCE-MRI) that can better select AKT-inhibition responders than immunohistochemistry (IHC)-based receptors and explore associated tumor microenvironment (TME). PATIENTS AND

methodsWe included 987 patients who underwent surgery following neoadjuvant chemotherapy (NACT) in the I-SPY2 trial, which comprised three cohorts: THI discovery, THI validation, and TME exploration. THI was constructed by regression on the consensus clustering labels using repeatable, reproducible, and specifically predictive radiomics-based features. The predictive value of THI for treatment outcomes was evaluated using AUC-ROC with cross-validation, while its clinical utility was assessed through Bayesian logistic regression. Additionally, we explored differentially expressed phosphoproteins, proteins, genes, biological mechanisms, and the tumor immune microenvironment.

resultsSeven repeatable image features were identified to be specifically predictive in the MK2206 arm and yielded two consensus clusters. The developed THI accurately predicted the two clusters, achieving an AUC-ROC of 1 in the discovery cohort and 0.99 in the remaining patients. It was significantly associated with treatment response in the AKT inhibition cohort with a cross-validation AUC of 0.73 (95% CI 0.63 to 0.83), and in corresponding subgroups (HER2−, HER2+, HR−) where AUCs ranged from 0.73 (95% CI 0.63 to 0.83) to 0.85 (95% CI 0.73 to 0.96). Bayesian analysis indicated that patients with high THI had a higher estimated average pCR rate of 56.1% in the AKT inhibition arm compared to 18.7% in the control arm (p < 0.001). Furthermore, high THI was associated with a "hot" tumor immune microenvironment, characterized by active immune pathways, extensive immune cell infiltration, and decreased cell cycle activity.

conclusionsThe Tumor Heterogeneity Index was found to be specifically and independently associated with the response to AKT inhibition, highlighting its potential to aid in responder prediction. Additionally, the associated tumor microenvironment enhances our understanding of the antitumor mechanisms underlying AKT inhibition.

Indexed as

Breast NeoplasmsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktTumor MicroenvironmentAdultBiomarkers, TumorDynamic Contrast Enhanced Magnetic Resonance ImagingFemaleHeterocyclic Compounds, 3-RingHumansMiddle AgedNeoadjuvant TherapyPathologic Complete ResponseRadiomicsBiomarkers, TumorHeterocyclic Compounds, 3-RingMK 2206Protein Kinase InhibitorsProto-Oncogene Proteins c-aktAKT inhibitionBreast cancerImaging biomarkerNeoadjuvant chemotherapy

Identifiers

PMID41645311
PMCPMC12874905

What Socratic holds

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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 Socratic graph.