Related Experiment Video
Updated: Dec 11, 2025
Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
Clinical implications of prospective genomic profiling of metastatic breast cancer patients
Courtney T van Geelen1, Peter Savas1,2, Zhi Ling Teo1
1Division of Research, Peter MacCallum Cancer Centre, Melbourne, Australia.
Background:
Metastatic breast cancer remains incurable. Next-generation sequencing (NGS) offers the ability to identify actionable genomic alterations in tumours which may then be matched with targeted therapies, but the implementation and utility of this approach is not well defined for patients with metastatic breast cancer.
Methods:
We recruited patients with advanced breast cancer of any subtype for prospective targeted NGS of their most recent tumour samples, using a panel of 108 breast cancer-specific genes. Genes were classified as actionable or non-actionable using the European Society of Medical Oncology Scale for Clinical Actionability of Molecular Targets (ESCAT) guidelines.
Results:
Between February 2014 and May 2019, 322 patients were enrolled onto the study, with 72% (n = 234) of patients successfully sequenced (n = 357 samples). The majority (74%, n = 171) of sequenced patients were found to carry a potentially actionable alteration, the most common being a PIK3CA mutation. Forty-three percent (n = 74) of patients with actionable alterations were referred for a clinical trial or referred for confirmatory germline testing or had a change in therapy outside of clinical trials. We found alterations in AKT1, BRCA2, CHEK2, ESR1, FGFR1, KMT2C, NCOR1, PIK3CA and TSC2 to be significantly enriched in our metastatic population compared with primary breast cancers. Concordance between primary and metastatic samples for key driver genes (TP53, ERBB2 amplification) was > 75%. Additionally, we found that patients with a higher number of mutations had a significantly worse overall survival.
Conclusion:
Genomic profiling of patients with metastatic breast cancer can have clinical implications and should be considered in all suitable patients.
Insights
Genomic profiling using next-generation sequencing (NGS) in metastatic breast cancer patients identified actionable alterations in most cases. This approach can guide targeted therapies and clinical trial referrals, impacting patient treatment strategies.
Area of Science:
- Oncology
- Genomics
- Translational Research
Background:
- Metastatic breast cancer (MBC) is currently incurable.
- Next-generation sequencing (NGS) offers potential for identifying actionable genomic alterations in tumors.
- The clinical utility of NGS for MBC patients requires further definition.
Purpose of the Study:
- To prospectively evaluate the implementation and utility of targeted NGS in patients with advanced breast cancer.
- To identify actionable genomic alterations in MBC tumors and assess their potential for targeted therapy matching.
Main Methods:
- Prospective recruitment of advanced breast cancer patients across all subtypes.
- Targeted NGS of 108 breast cancer-specific genes using tumor samples.
- Classification of gene alterations based on European Society of Medical Oncology Scale for Clinical Actionability of Molecular Targets (ESCAT) guidelines.
Main Results:
- 72% of enrolled patients (234/322) underwent successful sequencing.
- 74% of sequenced patients (171/234) had potentially actionable alterations, with PIK3CA mutations being most common.
- 43% of patients with actionable alterations were referred for clinical trials, germline testing, or therapy changes.
- Specific gene alterations (e.g., AKT1, BRCA2, ESR1, PIK3CA) were enriched in the metastatic population.
- Higher mutation burden correlated with significantly worse overall survival.
Conclusions:
- Genomic profiling of metastatic breast cancer patients has significant clinical implications.
- Targeted NGS should be considered for all suitable patients with metastatic breast cancer.
- Identifying actionable alterations can guide treatment decisions and improve patient outcomes.
More Related Videos
10:27Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
07:41Performing Data Mining And Integrative Analysis Of Biomarker in Breast Cancer Using Multiple Publicly Accessible Databases
Published on: May 17, 2019
