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Published on: July 25, 2020
Identification of putative actionable alterations in clinically relevant genes in breast cancer
Pushpinder Kaur1,2, Tania B Porras3, Anthony Colombo4
1Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Background:
Individualising treatment in breast cancer requires effective predictive biomarkers. While relatively few genomic aberrations are clinically relevant, there is a need for characterising patients across different subtypes to identify actionable alterations.
Methods:
We identified genomic alterations in 49 potentially actionable genes for which drugs are available either clinically or via clinical trials. We explored the landscape of mutations and copy number alterations (CNAs) in actionable genes in seven breast cancer subtypes utilising The Cancer Genome Atlas. To dissect the genomic complexity, we analysed the patterns of co-occurrence and mutual exclusivity in actionable genes.
Results:
We found that >30% of tumours harboured putative actionable events that are targetable by currently available drugs. We identified genes that had multiple targetable alterations, representing candidate targets for combination therapy. Genes predicted to be drivers in primary breast tumours fell into five categories: mTOR pathway, immune checkpoints, oestrogen signalling, tumour suppression and DNA damage repair. Our analysis also revealed that CNAs in 34/49 (69%) and mutations in 13/49 (26%) genes were significantly associated with gene expression, validating copy number events as a dominant oncogenic mechanism in breast cancer.
Conclusion:
These results may enable the acceleration of personalised therapy and improve clinical outcomes in breast cancer.
Insights
Over 30% of breast cancers have actionable genomic alterations targetable by existing drugs. This study identifies key genes and pathways for personalized breast cancer therapy, potentially improving patient outcomes.
Area of Science:
- Genomics
- Oncology
- Translational Medicine
Background:
- Personalized breast cancer treatment necessitates predictive biomarkers.
- Identifying actionable genomic alterations across breast cancer subtypes is crucial.
Purpose of the Study:
- To analyze actionable genomic alterations in seven breast cancer subtypes.
- To identify potential targets for combination therapy and understand oncogenic mechanisms.
Main Methods:
- Analysis of mutations and copy number alterations (CNAs) in 49 actionable genes using The Cancer Genome Atlas.
- Examination of co-occurrence and mutual exclusivity patterns of actionable genes.
Main Results:
- Over 30% of tumors exhibited actionable genomic events targetable by current drugs.
- Identified genes with multiple alterations as candidates for combination therapy.
- Copy number alterations were a dominant oncogenic mechanism, significantly associated with gene expression.
Conclusions:
- Genomic profiling reveals significant potential for personalized breast cancer therapies.
- Findings support the acceleration of targeted treatments and improved clinical outcomes.
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