ArticleBreast cancer research and treatment2016
Trastuzumab improves tumor perfusion and vascular delivery of cytotoxic therapy in a murine model of HER2+ breast cancer: preliminary results.
Article in Breast cancer research and treatment, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Pooled it
- DB-1310, a HER3-targeting antibody-drug conjugate, has synergistic anti-tumor activity with trastuzumab in HER2- and HER3-expressing breast cancer.Cancer biology & medicine · 2025Article
- Amelioration of breast cancer therapies through normalization of tumor vessels and microenvironment: paradigm shift to improve drug perfusion and nanocarrier permeation.Drug delivery and translational research · 2025Review
- Dual anti-HER2/EGFR inhibition synergistically increases therapeutic effects and alters tumor oxygenation in HNSCC.Scientific reports · 2024Article
- The effect of tumor vascular remodeling and immune microenvironment activation induced by radiotherapy: quantitative evaluation with magnetic resonance/photoacoustic dual-modality imaging.Quantitative imaging in medicine and surgery · 2023Article
- Bridging Scales: a Hybrid Model to Simulate Vascular Tumor Growth and Treatment Response.ArXiv · 2023Article
- The Role of PET/CT in Breast Cancer.Diagnostics (Basel, Switzerland) · 2023Review
- Optimizing combination therapy in a murine model of HER2+ breast cancer.Computer methods in applied mechanics and engineering · 2022Article
- Nanotherapeutics Plus Immunotherapy in Oncology: Who Brings What to the Table?Pharmaceutics · 2022Review
- Resistance to Trastuzumab.Cancers · 2022Review
- Evaluating the efficacy and microenvironment changes of HER2 + gastric cancer during HLX02 and Endostar treatment using quantitative MRI.BMC cancer · 2022Article
- Article
- Quantifying Tumor Heterogeneity via MRI Habitats to Characterize Microenvironmental Alterations in HER2+ Breast Cancer.Cancers · 2022Article
- Modulation of the Tumor Microenvironment with Trastuzumab Enables Radiosensitization in HER2+ Breast Cancer.Cancers · 2022Article
- CD4 T-cell immune stimulation of HER2 + breast cancer cells alters response to trastuzumab in vitro.Cancer cell international · 2020Article
- Evaluating Trastuzumab in the treatment of HER2 positive breast cancer.Histology and histopathology · 2020Review
- Article
- Optimal Control Theory for Personalized Therapeutic Regimens in Oncology: Background, History, Challenges, and Opportunities.Journal of clinical medicine · 2020Review
- Anti-HER2 induced myeloid cell alterations correspond with increasing vascular maturation in a murine model of HER2+ breast cancer.BMC cancer · 2020Article
- Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
To employ in vivo imaging and histological techniques to identify and quantify vascular changes early in the course of treatment with trastuzumab in a murine model of HER2+ breast cancer. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to quantitatively characterize vessel perfusion/permeability (via the parameter K (trans) ) and the extravascular extracellular volume fraction (v e ) in the BT474 mouse model of HER2+ breast cancer (N = 20) at baseline, day one, and day four following trastuzumab treatment (10 mg/kg). Additional cohorts of mice were used to quantify proliferation (Ki67), microvessel density (CD31), pericyte coverage (α-SMA) by immunohistochemistry (N = 44), and to quantify human VEGF-A expression (N = 29) throughout the course of therapy. Longitudinal assessment of combination doxorubicin ± trastuzumab (N = 42) tested the hypothesis that prior treatment with trastuzumab will increase the efficacy of subsequent doxorubicin therapy. Compared to control tumors, trastuzumab-treated tumors exhibited a significant increase in K (trans) (P = 0.035) on day four, indicating increased perfusion and/or vessel permeability and a simultaneous significant increase in v e (P = 0.01), indicating increased cell death. Immunohistochemical and ELISA analyses revealed that by day four the trastuzumab-treated tumors had a significant increase in vessel maturation index (i.e., the ratio of α-SMA to CD31 staining) compared to controls (P < 0.001) and a significant decrease in VEGF-A (P = 0.03). Additionally, trastuzumab dosing prior to doxorubicin improved the overall effectiveness of the therapies (P < 0.001). This study identifies and validates improved perfusion characteristics following trastuzumab therapy, resulting in an improvement in trastuzumab-doxorubicin combination therapy in a murine model of HER2+ breast cancer. This data suggests properties of vessel maturation. In particular, the use of DCE-MRI, a clinically available imaging method, following treatment with trastuzumab may provide an opportunity to optimize the scheduling and improve delivery of subsequent cytotoxic therapy.
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Registered trials
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