Genomic spectra of lymphovascular invasion in breast cancer

• DOI: 10.21147/j.issn.1000-9604.2025.02.02
• Publication Date: 2025-05-13T09:02:16Z
• Authors: Chuhan Shen; ; Caijin Lin; Feilin Qu; Chao Chen; Zhiming Shao; Yizhou Jiang; Xin Hu; Genhong Di
• Keywords: Lymphovascular invasion; APOBEC; Triple-negative breast cancer

Lymphovascular invasion (LVI) is a crucial step in metastasis and closely associated with poor prognosis patients breast cancer. However, its clinical molecular characteristics remain insufficiently defined. We aimed to identify targets for LVI-positive (LVI+) cancer predict patient via the analysis of genomic variations using targeted sequencing. established large-scale sequencing cohort 4,079 samples, which included 3,159 early-stage locally advanced available LVI statuses. Comparisons somatic mutation frequencies germline pathogenic/likely pathogenic (P/LP) frequencies, mutational signature analyses, mutual exclusivity co-occurrence analyses were performed key features involved LVI+ patients. Additionally, Kaplan-Meier survival was conducted further explore prognostic value co-mutations cases. observed that hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) triple-negative (TNBC) subtypes exhibited worse disease-free survival. Notably, HR+/HER2- HER2+ displayed distinct compared LVI- tumors. Specifically, tumors greater mutations TP53 ESR1, BRCA2 P/LP variations, an enrichment clock-like single-base substitution (SBS)1 signatures. In contrast, demonstrated higher incidence PIK3CA increased activity apolipoprotein B mRNA editing enzyme catalytic polypeptide (APOBEC)-associated SBS2 signature. Furthermore, we revealed co-mutation NF1 could serve as potential marker Our findings provide comprehensive overview cancer, thereby offering insights may help refining precision treatment strategies