Evidence map›Paper›PMID 39272208›Full record

ArticleBreast cancer research : BCR2024

A triple hormone receptor ER, AR, and VDR signature is a robust prognosis predictor in breast cancer.

Mohamed Omar, J Chuck Harrell, Rulla Tamimi, Luigi Marchionni, Cihat Erdogan, Harikrishna Nakshatri, Tan A Ince

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Article in Breast cancer research : BCR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Mohamed OmarDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
J Chuck HarrellDepartment of Pathology, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Rulla TamimiDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
Luigi MarchionniDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
Cihat ErdoganCenter for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Harikrishna NakshatriDepartments of Surgery, Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Tan A InceDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA. tai9015@med.cornell.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDespite evidence indicating the dominance of cell-of-origin signatures in molecular tumor patterns, translating these genome-wide patterns into actionable insights has been challenging. This study introduces breast cancer cell-of-origin signatures that offer significant prognostic value across all breast cancer subtypes and various clinical cohorts, compared to previously developed genomic signatures.

methodsWe previously reported that triple hormone receptor (THR) co-expression patterns of androgen (AR), estrogen (ER), and vitamin D (VDR) receptors are maintained at the protein level in human breast cancers. Here, we developed corresponding mRNA signatures (THR-50 and THR-70) based on these patterns to categorize breast tumors by their THR expression levels. The THR mRNA signatures were evaluated across 56 breast cancer datasets (5040 patients) using Kaplan-Meier survival analysis, Cox proportional hazard regression, and unsupervised clustering.

resultsThe THR signatures effectively predict both overall and progression-free survival across all evaluated datasets, independent of subtype, grade, or treatment status, suggesting improvement over existing prognostic signatures. Furthermore, they delineate three distinct ER-positive breast cancer subtypes with significant survival in differences-expanding on the conventional two subtypes. Additionally, coupling THR-70 with an immune signature identifies a predominantly ER-negative breast cancer subgroup with a highly favorable prognosis, comparable to ER-positive cases, as well as an ER-negative subgroup with notably poor outcome, characterized by a 15-fold shorter survival.

conclusionsThe THR cell-of-origin signature introduces a novel dimension to breast cancer biology, potentially serving as a robust foundation for integrating additional prognostic biomarkers. These signatures offer utility as a prognostic index for stratifying existing breast cancer subtypes and for de novo classification of breast cancer cases. Moreover, THR signatures may also hold promise in predicting hormone treatment responses targeting AR and/or VDR.

Indexed as

Biomarkers, TumorBreast NeoplasmsReceptors, AndrogenReceptors, CalcitriolReceptors, EstrogenFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimatePrognosisTranscriptomeAR protein, humanBiomarkers, TumorReceptors, AndrogenReceptors, CalcitriolReceptors, EstrogenVDR protein, humanAndrogen receptorBreast cancerBreast cancer subtypesCell-of-originEstrogen receptorPredictive modelingSurvivalTriple hormone receptorVitamin D receptor

Identifiers

PMID39272208
PMCPMC11395215

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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.