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HER2-Targeted Therapy Reduces Incidence and Progression of Midlife Mammary Tumors in Female Murine Mammary Tumor Virus huHER2-Transgenic Mice
Open accessAbstract
PURPOSE: This study examined the effectiveness of early and prolonged mu4D5 (the murine form of trastuzumab/Herceptin) treatment in transgenic mice that overexpress human HER2 (huHER2), under the murine mammary tumor virus promoter, as a model of huHER2-overexpressing breast cancer. EXPERIMENTAL DESIGN: Mice were randomly assigned to one of three treatment groups and received i.p. injections from 17 weeks of age until either 52 weeks of age or morbidity. Fourteen mice received 100 mg/kg mu4D5, 14 mice received 100 mg/kg antiherpes simplex virus glycoprotein D control antibody, and 11 mice received a diluent control. RESULTS: High levels of huHER2 expression were detectable in mammary glands of young virgin founder mice. Mammary adenocarcinomas were frequently found in female founders and progeny at an average age of 28 weeks, with some progressing to metastatic disease. The incidence of mammary tumors was significantly reduced, and tumor growth inhibition was observed in mice receiving mu4D5 compared with control mice. In addition, Harderian gland neoplasms, highly associated with overexpression of huHER2 in this transgenic line, were entirely absent in the mu4D5 treatment group, indicating down-regulation of huHER2 in vivo activity. CONCLUSIONS: Early intervention with mu4D5 was of benefit in our transgenic mice at high risk for developing huHER2-overexpressing breast cancer. This study suggests a potential benefit of early treatment with Herceptin in HER2-positive primary breast cancer.
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“Consistent with its oncogenic activity, overexpression of wild-type Neu or HER2 under the control of a mammary-specific promoter leads to metastatic mammary tumors in transgenic mice (Andrechek et al., 2000; Finkle et al., 2004).”
From ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics (2014) · cites this paper as Finkle et al., 2004
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Metadata
- Authors
- Finkle, D., Quan, Z. R., Asghari, V., Kloss, J., Ghaboosi, N., Mai, E., Wong, W. L., Hollingshead, P., Schwall, R., Koeppen, H., & Erickson, S.
- Affiliations
- 1Physiology, Departments of
- 2Assay and Automation Technology,
- Molecular Oncology (United States) (US)
- Genentech (US)
- Venue
- Clinical Cancer Research
- Published
- 2004-04-01
- Volume
- 10
- Issue
- 7
- Pages
- 2499-2511
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2166433072
- Cited by
- 125
- References
- 33
- Citations by year
- 2025: 5 · 2024: 4 · 2023: 15 · 2022: 1 · 2021: 6 · 2020: 7 · 2019: 5 · 2018: 2 · 2017: 6 · 2016: 11 · 2015: 7 · 2014: 9 · 2013: 6 · 2012: 4
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Genentech
- Topics
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Oncology › Gastric Cancer Management and Outcomes
- Keywords
- HER2, trastuzumab, HER2-positive breast cancer, early intervention, tumor incidence, tumor progression, metastasis
- MeSH terms
- Trastuzumab, Animals, Antibodies, Monoclonal, Base Sequence, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immunohistochemistry, Lung Neoplasms, Mammary Tumor Virus, Mouse, Mice, Transgenic, Models, Genetic, Molecular Sequence Data, Neoplasm Metastasis, Neoplasms, Experimental, Promoter Regions, Genetic, RNA, RNA, Messenger, Time Factors, Down-Regulation, Mammary Neoplasms, Animal, In Situ Hybridization, Fluorescence, Disease Progression, Receptor, ErbB-2, Erb-b2 Receptor Tyrosine Kinases, Transgenes, Reverse Transcriptase Polymerase Chain Reaction, Mice, Antibodies, Monoclonal, Humanized
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