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

Jia-Wern Pan,Oscar M Rueda,Bethan Sandey,Cheng-Har Yip,Stephen-John Sammut,Mei-Yee Meng,Pathmanathan Rajadurai,Muhammad Mamduh Ahmad Zabidi,Siti Norhidayu Hasan,Pei-Sze Ng,Carlos Caldas,Soo-Hwang Teo,Suet-Feung Chin

doi:10.1038/s41467-020-20173-5

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.

Highlights

Molecular profiling of breast cancer has enabled the development of more robust molecular prognostic signatures and therapeutic options for breast cancer patients
Relative to Caucasian women, we found a higher prevalence of human epidermal growth factor receptor 2 (HER2)-enriched molecular subtypes, as well as a higher prevalence of TP53 somatic mutations in ER+ Asian breast tumours
Primary tumour tissue and blood samples were obtained from 560 female patients with breast cancer treated at the Subang Jaya Medical Centre (SJMC), Malaysia between 2012 and 2017 who were recruited to the Malaysian Breast Cancer (MyBrCa) study[20]

Summary

Introduction

Molecular profiling of breast cancer has enabled the development of more robust molecular prognostic signatures and therapeutic options for breast cancer patients. 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. 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. A recent genomic analysis of 187 early-onset Asian breast cancers show a higher prevalence of TP53 mutations and enrichment in immune signatures[19]. Analysis of 465 triple-negative breast cancers in Chinese women demonstrated broad similarities in tumours of the same subtype arising in Asian and Caucasian women, Chinese patients had a significantly higher proportion of the luminal androgen receptor (LAR) subtype of TNBCs relative to Caucasian or AfricanAmerican patients[9]

Methods

Results

Conclusion