Genomic landscape of circulating tumor DNA in HER2-low metastatic breast cancer

IF 40.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Zongbi Yi, Kaixiang Feng, Dan Lv, Yanfang Guan, Youcheng Shao, Fei Ma, Binghe Xu
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引用次数: 0

Abstract

The large population of HER2-low breast cancer patients necessitates further research to provide enhanced clinical guidance. In this study, we retrospectively analyzed 1071 metastatic breast cancer (MBC) patients and the circulating tumor DNA (ctDNA) to investigate clinicopathological and genetic alterations of HER2-low MBC patients. The effect of HER2-low status on different treatment modalities was explored in two prospective clinical trials (NCT03412383, NCT01917279) and a retrospective study. Our findings suggest TP53, PIK3CA, and ESR1 are frequently mutated genes in HER2-low MBC. Compared to the HER2-0 group, mutations observed in the HER2-low group are more closely associated with metabolic pathway alterations. Additionally, among patients with ERBB2 mutations and treated with pyrotinib, the HER2-low group may experience superior prognosis when compared to the HER2-0 group. Notably, we did not find any statistically significant disparity in the response to chemotherapy, endocrine therapy, or CDK4/6 inhibitor therapy between HER2-0 and HER2-low breast cancer patients. Interestingly, within the subgroup of individuals with metabolic pathway-related gene mutations, we found that HER2-low group exhibited a more favorable response to these treatments compared to HER2-0 group. Additionally, dynamic analysis showed the HER2-low MBC patients whose molecular tumor burden index decreased or achieved early clearance of ctDNA after the initial two treatment cycles, exhibited prolonged survival. Moreover, we classified HER2-low MBC into three clusters, providing a reference for subsequent treatment with enhanced precision. Our study offers valuable insights into the biology of HER2-low MBC and may provide reference for personalized treatment strategies.

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来源期刊
Signal Transduction and Targeted Therapy
Signal Transduction and Targeted Therapy Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
44.50
自引率
1.50%
发文量
384
审稿时长
5 weeks
期刊介绍: Signal Transduction and Targeted Therapy is an open access journal that focuses on timely publication of cutting-edge discoveries and advancements in basic science and clinical research related to signal transduction and targeted therapy. Scope: The journal covers research on major human diseases, including, but not limited to: Cancer,Cardiovascular diseases,Autoimmune diseases,Nervous system diseases.
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