Biomarkers of everolimus efficacy in breast cancer therapy

Abstract

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. 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. 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. 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.