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Biomarkers of everolimus efficacy in breast cancer therapy
1Algoma District Cancer Program, 10066Sault Area Hospital, Sault Ste. Marie, Ontario, Canada, and Section of Internal Medicine, Division of Clinical Sciences, Northern Ontario School of Medicine, Sudbury, Ontario, Canada.
Objective:
Everolimus is an inhibitor of serine/ threonine kinase mTOR. The drug is approved for the treatment of metastatic ER positive, HER2 negative breast cancers and benefits a subset of patients with these breast cancers in combination with hormonal therapies. Despite extensive efforts, no additional predictive biomarkers to guide therapeutic decisions for everolimus have been introduced in clinical practice.
Data Sources:
This paper discusses predictive biomarkers for everolimus efficacy in breast cancer. A search of the medline and web of science databases was performed using the words "everolimus" and "biomarkers". References of retrieved articles were manually scanned for additional relevant articles.
Data Summary:
Everolimus benefits a subset of patients with metastatic ER positive, HER2 negative breast cancers in combination with hormonal therapies. Despite extensive efforts no additional predictive biomarkers to guide therapeutic decisions for everolimus therapy have been confirmed for use in clinical practice. However, promising biomarker leads for everolimus efficacy in breast cancer have been suggested and include expression of proteins in the mTOR pathway in ER positive, HER2 negative breast cancers. In HER2 positive cancers PIK3CA mutations, and PTEN expression loss are prognostic. Other clinical predictive biomarkers with more limited data include characteristics derived from whole genome sequencing, subsets of circulating leukocytes and changes in Standardized Uptake Values (SUV) of Positron Emission Tomography (PET) scans.
Conclusions:
Putative predictive biomarkers for everolimus efficacy in breast cancer patients, both genomic and clinical, deserve further study and could lead to a better selection of responsive patients.
Insights
Predictive biomarkers for everolimus in breast cancer are crucial for patient selection. Further research into genomic and clinical markers could improve treatment outcomes for metastatic breast cancer.
Area of Science:
- Oncology
- Pharmacogenomics
- Biomarker Discovery
Background:
- Everolimus, an mTOR inhibitor, treats metastatic ER-positive, HER2-negative breast cancer.
- Current clinical practice lacks predictive biomarkers for everolimus therapy.
- Everolimus benefits only a subset of patients, necessitating better patient selection.
Purpose of the Study:
- To review predictive biomarkers for everolimus efficacy in breast cancer.
- To identify promising genomic and clinical markers for guiding everolimus treatment decisions.
Main Methods:
- Literature search of Medline and Web of Science databases using keywords 'everolimus' and 'biomarkers'.
- Manual scanning of retrieved article references for additional relevant studies.
Main Results:
- Promising biomarkers include mTOR pathway proteins in ER-positive, HER2-negative breast cancer.
- PIK3CA mutations and PTEN loss are prognostic in HER2-positive cancers.
- Other potential markers include whole genome sequencing, leukocyte subsets, and PET scan SUV changes.
Conclusions:
- Genomic and clinical biomarkers show potential for predicting everolimus response.
- Further investigation is needed to validate these biomarkers for clinical use.
- Improved biomarker selection could enhance treatment efficacy for breast cancer patients.
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