Prognostic significance of ctDNA mutations in advanced HER2-positive breast cancer treated with targeted therapy: A meta-analysis

作者：Jialin Lin, Hangcheng Xu, Yiran Zhou, Qiang Sa, Jiayu Wang, Binghe Xu · 发表于：Advances in Clinical and Experimental Medicine · 年份：2026 · DOI：10.17219/acem/209957 · 研究领域：Cancer Genomics and Diagnostics、Lung Cancer Treatments and Mutations、Advanced Breast Cancer Therapies

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising noninvasive biomarker in advanced breast cancer. In patients with advanced HER2-positive disease, responses to targeted therapy vary. The prognostic significance of ctDNA mutations across different genes and treatment regimens remains to be fully clarified. OBJECTIVES: This meta-analysis evaluated the predictive role of ctDNA mutations in guiding anti-HER2 therapy. MATERIAL AND METHODS: We searched PubMed, Embase, the Cochrane Library, and major oncology conference proceedings for studies evaluating associations between ctDNA and progression-free survival (PFS) or overall survival (OS) in breast cancer. Pooled hazard ratios (HRs) and odds ratios (ORs) were calculated using a pre-specified random-effects model. Study quality, publication bias, and robustness were assessed using the Newcastle-Ottawa Scale (NOS), funnel plots, Egger's test, and leave-one-out analyses. RESULTS: A total of 12 studies involving 558 patients were included. Baseline ctDNA mutation status was significantly associated with shorter PFS (HR = 1.73, 95% confidence interval (95% CI): 1.06-2.82, p = 0.03). PIK3CA mutations correlated with worse PFS (HR = 2.12, 95% CI: 1.43-3.15, p = 0.002), whereas ERBB2 mutations showed no significant association. ctDNA mutations predicted poorer PFS in tyrosine kinase inhibitor (TKI)-treated patients (HR = 2.04, 95% CI: 1.29-3.24, p = 0.002), particularly in patients receiving pyrotinib (HR = 2.77, 95% CI: 1.96-3.92...