Abstract 2492: Unique genomic and transcriptomic characteristics in young Chinese patients with HR+/HER2- invasive breast cancer
Authors: Hu Hong , Hu Zhenyu , Liu Ke , Hu Jintao , Li Fengyu , Cao Boyang , Shao Kang , Shi Wenzhao , Feng Gang , Zhou Wenbin 
Published: September 2020

Abstract
Hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) is generally associated with a more favorable outcome in breast cancer, where age may play roles in the prognosis of invasive breast cancer. Earlier studies have found that the effect of age on the outcomes varied by tumor subtypes. Younger patients (&lt; 40 years of age) were associated with significant increases in risk of breast cancer death with HR+/HER2- tumors comparing to their older counterpart. Although it has been observed in a clinical setting, the involved signaling pathways and driver genes remain unknown at a genomic level. In this study, in order to seek the relevance of unique genomic features and gene expression signatures in young HR+/HER2- breast cancer patients (&lt;40 years old), we conducted whole genomic sequencing and transcriptomic sequencing of two cohorts of primary HR+/HER2- invasive breast cancer patients in China, relatively young group (age &lt; 40 at diagnosis, ranging 34-39, N=25) and old group (age ≥50 at diagnosis, ranging 53-68, N=26). There was no statistically significant difference in ki67 and TMB between two groups. We then performed comprehensive analysis and comparison of two cohorts on somatic mutation, copy number aberrations, and differential gene expression using Sentieon somatic mutation pipeline, Sequenza and HISAT2-StringTie-Ballgown pipeline. At genomic level, we found that the recurrent somatic alterations in some genes (particularly GATA3, ERBB2, TP53) were higher in young patients than in old patients with HR+/HER2- invasive breast cancer, while PIK3CA mutation associated with improved outcome was lower in young patients. Furthermore, the copy number aberrations localized at some critical regions, such as 14q11.2-13.1, were more frequent in young patients than in older patients. The coding genes in the featured chromosome regions were involved in multiple biological functions, such as cell proliferation and cell motility, and critically associated with prognosis. RNAseq-based differential gene expression analysis further confirmed the difference in the pathway developments between young and old patients. In conclusion, our study revealed specific genomic and transcriptomic characteristics in young breast cancer patients with HR+/HER2- invasive breast cancer compared to their old counterpart. The results indicated that the younger patients who carry these candidate risk genomic and transcriptomic features may lead to poor prognosis outcomes.
Citation Format: Hong Hu, Zhenyu Hu, Ke Liu, Jintao Hu, Fengyu Li, Boyang Cao, Kang Shao, Wenzhao Shi, Gang Feng, Wenbin Zhou. Unique genomic and transcriptomic characteristics in young Chinese patients with HR+/HER2- invasive breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2492.