Related Experiment Video
Updated: Jun 16, 2026
Modeling Brain Metastasis by Internal Carotid Artery Injection of Cancer Cells
Published on: August 2, 2022
[Management of metastatic HER2-positive breast cancer: present and future]
1Département d'oncologie médicale, centre de lutte contre le cancer Georges-François-Leclerc, 1, rue Professeur-Marion, 21000 Dijon, France.
Abstract:
HER2-positive breast cancer accounts for 20 to 25% of breast cancers. The surexpression of this tyrosine-kinase receptor is often associated with a poor prognosis. However, the management and the outcome of these patients have changed these last ten years with trastuzumab. Despite the encouraging results obtained with this humanized monoclonal antibody directed against the HER2-receptor, used alone or in association with chemotherapy in metastatic patients, progression under trastuzumab are usually observed and resistances to this treatment are described. Thus, many other monoclonal antibodies and tyrosine-kinase inhibitors emerged. These therapeutics, used alone or in association with chemotherapy or trastuzumab have variable properties: anti-HER2 and anti-EGFR such as lapatinib, pertuzumab and neratinib; anti-EGFR such as erlotinib and gefitinib; antiangiogenesis (bevacizumab, pazopanib); anti-mTOR pathway (temsirolimus, everolimus) or inhibitor of HSP90 (tanespimycine). In this paper, we present an overview on validated targeted therapies and those which are currently under investigation and seem promising in first line or after progression under trastuzumab. Data regarding cardiotoxicity and the use of trastuzumab under particular clinical circumstances (brain metastases, pregnancy) are also reviewed.
Insights
HER2-positive breast cancer treatment has advanced with trastuzumab, but resistance necessitates new targeted therapies. This review covers approved and investigational drugs for HER2-positive breast cancer, including those used after trastuzumab progression.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- HER2-positive breast cancer, comprising 20-25% of all breast cancers, is often linked to poor prognosis due to HER2 tyrosine-kinase receptor overexpression.
- Trastuzumab has significantly improved outcomes in the last decade, but resistance and progression remain clinical challenges.
Purpose of the Study:
- To provide an overview of validated and investigational targeted therapies for HER2-positive breast cancer.
- To discuss therapeutic strategies for first-line treatment and after progression on trastuzumab.
- To review cardiotoxicity and specific clinical applications of trastuzumab.
Main Methods:
- Literature review of targeted therapies for HER2-positive breast cancer.
- Analysis of clinical data on approved and investigational agents.
- Synthesis of information on drug mechanisms, efficacy, and resistance patterns.
Main Results:
- Trastuzumab has transformed HER2-positive breast cancer management, yet resistance necessitates alternative treatments.
- A range of targeted therapies, including monoclonal antibodies and tyrosine-kinase inhibitors, are available or under investigation.
- These agents target HER2, EGFR, angiogenesis, mTOR, and HSP90 pathways, offering options alone or in combination.
Conclusions:
- Despite advances, overcoming resistance to HER2-targeted therapies remains crucial.
- Newer agents and combination strategies show promise for improving outcomes in HER2-positive breast cancer.
- Careful consideration of cardiotoxicity and specific patient populations is essential for optimal treatment.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against specific...
02:30Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
02:56Treatment Resistant Cancers
02:56Treatment Resistent Cancers