Clustering of HR+/HER2- breast cancer in an Asian cohort is driven by immune phenotypes
Breast Cancer Research(2023)
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.
### Competing Interest Statement
The authors have declared no competing interest.
* MyBrCa
: the Malaysian Breast Cancer cohort
HRD
: homologous recombination deficiency
TNBC
: triple negative breast cancer
RNA-seq
: RNA sequencing
CNA
: copy number aberration
GSVA
: gene set variation analysis
SBS
: Single Base Substitutions
SNV
: single nucleotide variation
GSEA
: gene set enrichment analysis
IFN-γ
: interferon gamma
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