Item request has been placed! ×
Item request cannot be made. ×
loading  Processing Request

Mutational Landscape Assessed in Tumor Tissue and Circulating Tumor DNA During Treatment of Patients with HER2/ERBB2-Mutated Solid Tumors.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read Online Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 100967800 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2407 (Electronic) Linking ISSN: 14712407 NLM ISO Abbreviation: BMC Cancer Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : BioMed Central, [2001-
    • Subject Terms:
      Erb-b2 Receptor Tyrosine Kinases*/genetics ; Erb-b2 Receptor Tyrosine Kinases*/antagonists & inhibitors ; Neoplasms*/genetics ; Neoplasms*/drug therapy ; Neoplasms*/blood ; Circulating Tumor DNA*/genetics ; Circulating Tumor DNA*/blood ; Mutation*; Biomarkers, Tumor/genetics ; Humans ; Female ; Middle Aged ; Aged ; Male ; Adult ; Exome Sequencing ; Prospective Studies ; Aged, 80 and over ; Molecular Targeted Therapy ; Treatment Outcome
    • Abstract:
      Background: Human epidermal growth factor receptor 2 (HER2) aberrations, such as protein overexpression and amplification of the HER2 gene (ERBB2), are well-established in breast and gastroesophageal adenocarcinomas. However, ERBB2 oncogenic variants occur in 3.5% of all solid tumors with possible therapeutic implications. This study investigates the treatment efficacy and mutational landscape of patients with ERBB2-mutated cancers receiving HER2-targeted therapy.
      Methods: Nineteen patients with refractory solid tumors harboring ERBB2 oncogenic variants were enrolled in the Copenhagen Prospective Personalized Oncology trial and received HER2-targeted treatment. Whole-exome sequencing, ctDNA analysis, and imaging were conducted at baseline, during treatment, and upon progression. Descriptive statistics were employed due to the exploratory nature of the study.
      Results: HER2-targeted treatment yielded a 37% overall response rate, a 68% disease control rate, and a median progression-free survival of 4.4 months. A tendency was observed toward higher overall response rate (60%) in patients harboring ERBB2 oncogenic variants located in the tyrosine kinase domain. Clonality of ERBB2 oncogenic variants was linked with treatment efficacy, underscoring the reduced effect when targeting subclonal mutations. Sequential ctDNA analysis of ERBB2 oncogenic variants demonstrated correlation with treatment response.
      Conclusion: In this heterogeneous cohort of patients harboring ERBB2 oncogenic variants, HER2-targeted therapy demonstrated clinical efficacy. Mutational analysis revealed the importance of clonal ERBB2 oncogenic variants and identified factors influencing treatment outcomes. Limitations include a small sample size as well as heterogeneity in treatment regimens and cancer types.
      (© 2025. The Author(s).)
    • Abstract:
      Declarations. Competing interests: KE: Travel Expenses: AstraZeneca, Daiichi Sankyo, MSD Teaching: Astellas Pharma, Daiichi Sankyo IS: Research support (paid to institution) from Amgen, AstraZeneca, Bayer, BioInvent, BioNTech, Boehringer Ingelheim, Bristol-Myers Squibb, CDR Life, Dragonfly Therapeutics, Eli Lilly, Genentech, Genmab, Incyte, Monta Bioscience, MSD, Novartis, Orion, Pfizer, Puma Biotechnology, Repare Therapeutics, Roche. Honoraria: AstraZeneca. Support for travel, accommodation, and congress registration: AstraZeneca and Incyte. KSR: Research support (paid to institution) from Amgen, AstraZeneca, Bayer, BioInvent, BioNTech, Black Diamond Therapeutics, Bristol Myers Squibb, CDR Life, Dragonfly Therapeutics, Eli Lilly, Genentech, Genmab, Incyte, Merck, Monta Bioscience, Merk Sharp & Dohme, Navire, Novartis MH: Research support (paid to institution) from Amgen, AstraZeneca, Bayer, BioInvent, BioNTech, Black Diamond Therapeutics, Bridge Bio Oncology, Bristol Myers Squibb, CDR Life, Dragonfly Therapeutics, Eli Lilly, Genentech, Genmab, Incyte, Kinnate Biopharma, Merck, Monta Bioscience, Merk Sharp & Dohme, Navire, Novartis, Pfizer, Repare Therapeutics and Servier Oncology. Travel expenses: Repare Therapeutics MR: Consulting or Advisory Role: AstraZeneca, MSD. Research Funding: AstraZeneca (Inst), Pfizer, Servier, and Repare; consulting or advisory roles for AbbVie, Bayer, Roche, and Novartis. ES-R has received research grants (paid to institution) from Roche, Sanofi and Takeda; honoraria for lectures (paid to institution) from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Roche, and Takeda; and payment for participation in Advisory Board (paid to institution) from Roche and Takeda. MMS has served on an advisory board for PUMA Biotechnologies and received an unrestricted research grant from PUMA Biotechnologies. Others authors have no COI to declare.
    • References:
      Cancer Med. 2022 Jul;11(14):2767-2778. (PMID: 35393784)
      Clin Cancer Res. 2019 Feb 15;25(4):1239-1247. (PMID: 30274980)
      Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14476-81. (PMID: 22908275)
      NPJ Breast Cancer. 2022 Feb 18;8(1):22. (PMID: 35181666)
      J Oncol. 2020 Mar 7;2020:6375956. (PMID: 32256585)
      Clin Cancer Res. 2017 Oct 1;23(19):5687-5695. (PMID: 28679771)
      Genet Med. 2022 May;24(5):986-998. (PMID: 35101336)
      Cancer Discov. 2020 Feb;10(2):198-213. (PMID: 31806627)
      Nat Rev Clin Oncol. 2024 Sep;21(9):675-700. (PMID: 39039196)
      Ann Oncol. 2015 Jul;26(7):1421-7. (PMID: 25899785)
      Oncotarget. 2018 Jan 12;9(11):9741-9750. (PMID: 29515767)
      ESMO Open. 2019 Nov 13;4(6):e000583. (PMID: 31798980)
      Lancet. 2010 Aug 28;376(9742):687-97. (PMID: 20728210)
      Cancer Drug Resist. 2022 Sep 1;5(4):873-881. (PMID: 36627899)
      Clin Cancer Res. 2022 Apr 1;28(7):1258-1267. (PMID: 35046057)
      Eur J Cancer. 2009 Jan;45(2):228-47. (PMID: 19097774)
      Cancer Cell. 2018 Nov 12;34(5):792-806.e5. (PMID: 30449325)
      Br J Cancer. 2019 Jul;121(2):125-130. (PMID: 31186525)
      Clin Cancer Res. 2018 Oct 15;24(20):5112-5122. (PMID: 29967253)
      Ann Oncol. 2023 Oct;34(10):885-898. (PMID: 37597578)
      J Clin Oncol. 2018 Aug 20;36(24):2532-2537. (PMID: 29989854)
      Nature. 2018 Feb 8;554(7691):189-194. (PMID: 29420467)
      Nat Commun. 2023 Feb 6;14(1):630. (PMID: 36746967)
      N Engl J Med. 2001 Mar 15;344(11):783-92. (PMID: 11248153)
      Gynecol Oncol. 2024 Feb;181:162-169. (PMID: 38211393)
      NPJ Breast Cancer. 2020 Oct 30;6:59. (PMID: 33145402)
    • Contributed Indexing:
      Keywords: Cancer; ERBB2; HER2; Mutations; ctDNA
    • Accession Number:
      EC 2.7.10.1 (Erb-b2 Receptor Tyrosine Kinases)
      0 (Circulating Tumor DNA)
      0 (Biomarkers, Tumor)
      EC 2.7.10.1 (ERBB2 protein, human)
    • Publication Date:
      Date Created: 20250807 Date Completed: 20250807 Latest Revision: 20260127
    • Publication Date:
      20260130
    • Accession Number:
      PMC12330086
    • Accession Number:
      10.1186/s12885-025-14599-7
    • Accession Number:
      40770324