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The molecular landscape of Asian breast cancers reveals clinically relevant population-specific differences.

Published version
Peer-reviewed

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Authors

Pan, Jia-Wern 
Zabidi, Muhammad Mamduh Ahmad 
Ng, Pei-Sze 
Meng, Mei-Yee 
Hasan, Siti Norhidayu 

Abstract

Molecular profiling of breast cancer has enabled the development of more robust molecular prognostic signatures and therapeutic options for breast cancer patients. However, non-Caucasian populations remain understudied. Here, we present the mutational, transcriptional, and copy number profiles of 560 Malaysian breast tumours and a comparative analysis of breast cancers arising in Asian and Caucasian women. Compared to breast tumours in Caucasian women, we show an increased prevalence of HER2-enriched molecular subtypes and higher prevalence of TP53 somatic mutations in ER+ Asian breast tumours. We also observe elevated immune scores in Asian breast tumours, suggesting potential clinical response to immune checkpoint inhibitors. Whilst HER2-subtype and enriched immune score are associated with improved survival, presence of TP53 somatic mutations is associated with poorer survival in ER+ tumours. Taken together, these population differences unveil opportunities to improve the understanding of this disease and lay the foundation for precision medicine in different populations.

Description

Keywords

Asian People, Breast Neoplasms, Female, Genetics, Population, Genome, Human, Humans, Mutation, Receptor, ErbB-2, Receptors, Estrogen, Survival Analysis, Tumor Microenvironment, Tumor Suppressor Protein p53, White People

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

11

Publisher

Springer Science and Business Media LLC
Sponsorship
Cancer Research UK (CB4140)
Medical Research Council (MR/P012442/1)
Wellcome Trust (106566/Z/14/Z)
Cancer Research UK (16942)
Wellcome Trust (203477/Z/16/Z)
Scientex Foundation, Estée Lauder Companies, Yayasan Petronas, and Yayasan Sime Darby
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