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Predictive biomarkers in the treatment of HER2-positive breast cancer: an ongoing challenge
Tiziana Triulzi1, Giulia Valeria Bianchi2, Elda Tagliabue1
1Molecular Targeting Unit, Department of Experimental Oncology & Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Abstract:
The transmembrane tyrosine kinase receptor HER2 is overexpressed in 20% of invasive breast cancers and is associated with more aggressive disease. Until the advent of targeted agents, HER2 was associated with worse outcome. Trastuzumab, a recombinant humanized anti-HER2 monoclonal antibody, combined with chemotherapy improves disease-free and overall survival in both primary and metastatic tumors and represents a foundation of care for patients with HER2-positive breast cancers. However, a sizeable number of patients do not respond to this reagent, indicating the need for a biomarker able to recognize resistant tumors. Here, we review various studies on mechanisms of action and resistance to trastuzumab that have proven relevant in understanding how tumor care can be tailored to all HER2-positive patients.
Insights
HER2-positive breast cancer treatment with trastuzumab improves survival, but resistance necessitates new biomarkers. Understanding trastuzumab resistance mechanisms is key to tailoring care for all HER2-positive patients.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- HER2 overexpression in 20% of invasive breast cancers correlates with aggressive disease.
- Trastuzumab, an anti-HER2 monoclonal antibody, is a cornerstone therapy for HER2-positive breast cancer, improving survival with chemotherapy.
- A significant subset of patients exhibit primary or acquired resistance to trastuzumab, highlighting a critical unmet need.
Purpose of the Study:
- To review the mechanisms of action and resistance to trastuzumab in HER2-positive breast cancer.
- To identify potential biomarkers for predicting trastuzumab resistance.
- To inform strategies for personalized treatment of HER2-positive breast cancer patients.
Main Methods:
- Literature review of studies on HER2 signaling pathways.
- Analysis of clinical data on trastuzumab response and resistance.
- Examination of molecular mechanisms underlying trastuzumab efficacy and resistance.
Main Results:
- Trastuzumab efficacy is linked to HER2 receptor activity and downstream signaling pathways.
- Various mechanisms contribute to trastuzumab resistance, including HER2 amplification, mutations, and activation of alternative signaling pathways.
- Biomarkers for predicting response and resistance are under investigation.
Conclusions:
- Understanding trastuzumab resistance mechanisms is crucial for improving treatment outcomes.
- Development of predictive biomarkers will enable tailored therapeutic strategies for HER2-positive breast cancer.
- Further research into resistance pathways may lead to novel therapeutic targets.
