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Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
Published on: December 5, 2017
Targeting HER2 heterogeneity in breast cancer
Erika Hamilton1, Mythili Shastry2, S Michelle Shiller3
1Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN, United States.
Abstract:
The identification of Human epidermal growth factor receptor 2 (HER2) as a target in breast cancer and the subsequent development of HER2-targeted therapies has revolutionized the treatment of patients with HER2-positive breast cancer. However, there is an increasing awareness of how frequently tumors have low or heterogeneous expression of HER2. It is now recognized that this impacts the degree of benefit from HER2-targeted therapies. With the advent of novel and more potent antibody drug conjugates, targeting HER2 in traditional HER2-negative tumors with "HER2-low" expression is becoming possible. It is essential to refine the nomenclature around HER2 expression to enable clinicians to optimize treatment for patients across the HER2 expression spectrum in breast cancer. HER2 heterogeneity can be detected by conventional IHC, gene expression profiling or other methods and numerous studies have documented the correlation between the presence of HER2 heterogeneity and shorter disease-free survival (DFS) and overall survival (OS). Validation of techniques to identify HER2 heterogeneity in the clinic and concurrent development of agents to effectively treat tumors with non-uniform HER2 expression is needed.
Insights
New breast cancer treatments targeting Human Epidermal Growth Factor Receptor 2 (HER2) are emerging for HER2-low and heterogeneous tumors. Refining HER2 expression classification is crucial for optimizing patient care across the spectrum.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Human Epidermal Growth Factor Receptor 2 (HER2) targeted therapies have transformed HER2-positive breast cancer treatment.
- Increasing recognition of low or heterogeneous HER2 expression impacts treatment efficacy.
- Novel antibody drug conjugates enable targeting of HER2-low expressing tumors.
Purpose of the Study:
- To highlight the clinical significance of HER2 heterogeneity in breast cancer.
- To emphasize the need for refined nomenclature for HER2 expression.
- To underscore the necessity of developing new diagnostic and therapeutic strategies for HER2-low and heterogeneous breast cancers.
Main Methods:
- Review of current understanding of HER2 expression in breast cancer.
- Analysis of the impact of HER2 heterogeneity on treatment outcomes.
- Discussion of diagnostic methods for HER2 heterogeneity, including IHC and gene expression profiling.
Main Results:
- HER2 heterogeneity is increasingly recognized and affects response to HER2-targeted therapies.
- HER2 heterogeneity correlates with shorter disease-free survival (DFS) and overall survival (OS).
- Targeting HER2-low tumors with advanced therapies like antibody drug conjugates is becoming feasible.
Conclusions:
- Refined classification of HER2 expression is essential for personalized breast cancer treatment.
- Clinical validation of techniques to detect HER2 heterogeneity is required.
- Development of novel therapeutic agents for non-uniformly expressed HER2 tumors is needed.
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