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

Nat Commun. 2020 Dec 22;11(1):6433. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People / genetics*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Female
  • Genetics, Population*
  • Genome, Human
  • Humans
  • Mutation / genetics
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Survival Analysis
  • Tumor Microenvironment / immunology
  • Tumor Suppressor Protein p53 / genetics
  • White People / genetics

Substances

  • Receptors, Estrogen
  • Tumor Suppressor Protein p53
  • ERBB2 protein, human
  • Receptor, ErbB-2