Integrative molecular profiling identifies a novel cluster of ER‐positive breast cancer in very young women

Abstract

Very young breast cancer patients are more common in Asian countries than Western countries and are thought to have worse prognosis than older patients. The aim of the current study was to identify molecular characteristics of young patients with estrogen receptor (ER) positive breast cancer by analyzing mutations and copy number variants (CNV), and by applying expression profiling.

The whole exome and transcriptome of 47 Korean young breast cancer (KYBR) patients (age < 35) were analyzed. Genomic profiles were constructed using mutations, CNV and differential gene expression from sequencing data. Pathway analyses were also performed using gene sets to identify biological processes. Our data were also compared with young ER+ patients of TCGA breast cancer.

TP53, PIK3CA, and GATA3 were highly recurrent somatic mutation genes. APOBEC‐associated mutation signature was more frequent in KYBR compared with TCGA young patients. Integrative profiling classified our patients into three subgroups based on molecular characteristics. Group A showed luminal A‐like subtype and IGF1R signal dysregulation. Luminal B patients were classified into groups B and C, which showed chromosomal instability and enrichment for APOBEC3A/B deletions, respectively. Group B was characterized by 11q13 (CCND1) amplification and activation of ubiquitin‐mediated proteolysis pathway. Group C showed 17q12 (ERBB2) amplification, lower ER and progesterone receptor expression. Group C was also distinguished by immune activation and lower epithelial‐mesenchyme transition (EMT) degree compared with group B.

This study showed that integrative genomic profiling could classify very young patients with breast cancer into molecular subgroups that are potentially linked to different clinical characteristics.

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