The molecular landscape of Asian breast cancers reveals clinically relevant population-specific differences
Jia Wern Pan, Muhammad Mamduh Ahmad Zabidi, Pei-Sze Ng, Mei‐Yee Meng, Siti Norhidayu Hasan, Bethan Sandey, Stephen‐John Sammut, Cheng Har Yip, Pathmanathan Rajadurai, Oscar M. Rueda, Carlos Caldas, Suet‐Feung Chin, Soo‐Hwang Teo
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.