Introduction: The phosphoinositide triphosphate kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) is a central regulatory pathway involved in cell proliferation, growth, differentiation, metabolism and survival. Deregulation of this pathway is well described in breast cancer and is associated to the development of endocrine resistance among hormone receptor (HR)-positive tumors. Everolimus , an mTOR-inhibitor has clinical activity against breast cancer and has shown to restore sensitivity to endocrine therapy.
Areas covered: We review the clinical data and the results of the recently published clinical trials evaluating the use of everolimus in HR-positive breast cancer patients in combination with endocrine therapy. We discuss the data regarding efficacy but also describe in detail the side effect profile of this drug.
Expert opinion: Everolimus represents a new therapeutic alternative for the treatment of HR-positive metastatic breast cancer. Everolimus is in general a well-tolerated drug, however, stomatitis, fatigue and hematological abnormalities are common. It is still unclear if there are specific subgroups of patients that receive greater benefit from everolimus and whether there is a relationship between the presence of PIK3CA mutations and efficacy. The results of biomarker studies will hopefully provide information that will help us determine which patients are most likely to benefit from this treatment.