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Clustering of HR + /HER2- breast cancer in an Asian cohort is driven by immune phenotypes.

Published version
Peer-reviewed

Repository DOI


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Authors

Pan, Jia-Wern 
Ragu, Mohana 
Chan, Wei-Qin 
Hasan, Siti Norhidayu 
Islam, Tania 

Abstract

Breast cancer exhibits significant heterogeneity, manifesting in various subtypes that are critical in guiding treatment decisions. This study aimed to investigate the existence of distinct subtypes of breast cancer within the Asian population, by analysing the transcriptomic profiles of 934 breast cancer patients from a Malaysian cohort. Our findings reveal that the HR + /HER2- breast cancer samples display a distinct clustering pattern based on immune phenotypes, rather than conforming to the conventional luminal A-luminal B paradigm previously reported in breast cancers from women of European descent. This suggests that the activation of the immune system may play a more important role in Asian HR + /HER2- breast cancer than has been previously recognized. Analysis of somatic mutations by whole exome sequencing showed that counter-intuitively, the cluster of HR + /HER2- samples exhibiting higher immune scores was associated with lower tumour mutational burden, lower homologous recombination deficiency scores, and fewer copy number aberrations, implicating the involvement of non-canonical tumour immune pathways. Further investigations are warranted to determine the underlying mechanisms of these pathways, with the potential to develop innovative immunotherapeutic approaches tailored to this specific patient population.

Description

Funder: Cancer Research UK; doi: http://dx.doi.org/10.13039/501100000289


Funder: Scientex Foundation


Funder: Estée Lauder Companies


Funder: Vistage Malaysia


Funder: Yayasan PETRONAS


Funder: Yayasan Sime Darby; doi: http://dx.doi.org/10.13039/100019524

Keywords

Adult, Aged, Female, Humans, Middle Aged, Asian People, Biomarkers, Tumor, Breast Neoplasms, Cluster Analysis, Cohort Studies, DNA Copy Number Variations, Exome Sequencing, Gene Expression Profiling, Malaysia, Mutation, Phenotype, Receptor, ErbB-2, Receptors, Estrogen, Receptors, Progesterone, Transcriptome

Journal Title

Breast Cancer Res

Conference Name

Journal ISSN

1465-5411
1465-542X

Volume Title

26

Publisher

Springer Science and Business Media LLC
Sponsorship
Newton Fund (MR/P012442/1, MR/P012442/1)