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Updated: Mar 9, 2026
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Comprehensive genomic sequencing and the molecular profiles of clinically advanced breast cancer
Jeffrey S Ross1, Laurie M Gay2
1Foundation Medicine, Inc., Cambridge, MA, United States; Albany Medical College Albany, NY, United States.
Abstract:
Targeting specific mutations that have arisen within a tumour is a promising means of increasing the efficacy of treatments, and breast cancer is no exception to this new paradigm of personalised medicine. Traditional DNA sequencing methods used to characterise clinical cancer specimens and impact treatment decisions are highly sensitive, but are often limited in their scope to known mutational hot spots. Next-generation sequencing (NGS) technologies can also test for these well-known hot spots, as well as identifying insertions and deletions, copy number changes such as ERBB2 (HER2) gene amplification, and a wide array of fusion or rearrangement events. By rapidly analysing many genes in parallel, NGS technologies can make efficient use of precious biopsy material. Comprehensive genomic profiling (CGP) by NGS can reveal targetable, clinically relevant genomic alterations that can stratify tumours by predicted sensitivity to a variety of therapies, including HER2- or MTOR-targeted therapies, immunotherapies, and other kinase inhibitors. Many clinically relevant genomic alterations would not be identified by IHC or hotspot testing, but can be detected by NGS. In addition to the most common breast carcinoma subtypes, rare subtypes analysed with CGP also harbour clinically relevant genomic alterations that can potentially direct therapy selection, illustrating that CGP is a powerful tool for guiding treatment across all breast cancer subtypes.
Insights
Comprehensive genomic profiling using next-generation sequencing (NGS) identifies targetable mutations in breast cancer. This personalized medicine approach aids treatment selection across all breast cancer subtypes.
Area of Science:
- Oncology
- Genomics
- Personalized Medicine
Background:
- Targeting specific tumor mutations enhances treatment efficacy in breast cancer.
- Traditional DNA sequencing is limited to known mutational hotspots.
- Next-generation sequencing (NGS) offers broader genomic analysis.
Purpose of the Study:
- To evaluate the utility of comprehensive genomic profiling (CGP) by NGS in breast cancer.
- To identify clinically relevant genomic alterations for guiding therapy selection.
Main Methods:
- Utilizing next-generation sequencing (NGS) for comprehensive genomic profiling (CGP).
- Analyzing a wide range of genomic alterations including mutations, insertions, deletions, copy number changes (e.g., ERBB2 amplification), and gene fusions.
- Applying CGP across common and rare breast cancer subtypes.
Main Results:
- NGS-based CGP identifies targetable genomic alterations missed by traditional methods like IHC or hotspot testing.
- CGP reveals alterations that stratify tumors for therapies such as HER2-targeted treatments, mTOR inhibitors, and immunotherapies.
- Clinically relevant alterations are found in both common and rare breast cancer subtypes.
Conclusions:
- Comprehensive genomic profiling (CGP) by NGS is a powerful tool for personalized medicine in breast cancer.
- NGS-based CGP can guide treatment selection across all breast cancer subtypes by revealing actionable genomic alterations.
- This approach enhances the potential for effective therapy by identifying a wider spectrum of targetable genomic changes.
