ArticleJournal of translational medicine2025
Impacts of genomic alterations on the efficacy of HER2-targeted antibody-drug conjugates in patients with metastatic breast cancer.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Influence of HER2-low and HER2-zero status on pathologic complete response and survival in triple-negative breast cancer: a meta-analysis.Frontiers in oncology · 2025Pooled it
- Response to Lehrer.Journal of the National Cancer Institute · 2026Article
- Tumor genomics in patients younger than 40 years of age with metastatic breast cancer.NPJ precision oncology · 2026Article
- Clinical outcomes and genomic landscape of anti-HER2 antibody-drug conjugates in HER2-positive and HER2-low metastatic breast cancer.Therapeutic advances in medical oncology · 2026Article
- Learning Patient Similarity from Genomics for Precision Oncology.medRxiv : the preprint server for health sciences · 2025Article
- Next-generation sequencing in breast cancer: current clinical applications and future directions.Annals of medicine · 2025Review
- Observational
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
backgroundHER2-targeted antibody-drug conjugates (ADCs) have revolutionized the treatment landscape of metastatic breast cancer. However, the efficacy of these therapies may be compromised by genomic alterations. Hence, this study aims to identify factors predicting sensitivity to HER2 ADC in metastatic breast cancer.
methodsThis comprehensive real-world retrospective study collected clinical data from patients diagnosed with metastatic breast cancer and performed genomic profiling using targeted next-generation sequencing. The study analyzed the associations between genomic alterations and clinical outcomes of HER2 ADC treatment.
resultsSixty-three patients were included in this study, 33 with HER2-low breast cancer and 30 with HER2-positive breast cancer, respectively. The most frequently altered genes were TP53 (69%), PIK3CA (45%), MYC (35%), and ERBB2 (35%). Patients with amplifications in cell cycle-related genes showed inferior median progression-free survival (PFS) than those without amplifications (2.07 months vs. 8.40 months; HR = 5.24; 95% CI 2.11-13.01; p < 0.001), particularly in HER2-low patients (2.07 months vs. 8.27 months; HR = 4.23; 95% CI 1.50-11.91; p = 0.004). Additionally, ERBB2/CDK12 co-amplification exhibited a superior median PFS in all patients (19.33 months vs. 5.43 months; HR = 0.13; 95% CI 0.04-0.45; p < 0.001) and in HER2-positive patients (19.33 months vs. 6.87 months; HR = 0.18; 95% CI 0.05-0.72; p = 0.007). Multivariate analysis indicated that amplification in cell cycle-related genes was an independent predictor of inferior PFS (HR = 4.46; 95% CI 1.08-18.40; p = 0.039), while the presence of ERBB2/CDK12 co-amplification was independently correlated with superior PFS (HR = 0.16; 95% CI 0.04-0.65; p = 0.010).
conclusionsAmplification in cell cycle genes may contribute to primary resistance of HER2 ADC in HER2-low breast cancer. ERBB2/CDK12 co-amplification may be a potential biomarker for favorable responses in HER2-positive breast cancer.
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