title: Safety of mTOR inhibitors in breast cancer.
abstract: BACKGROUND
  Despite advances in the treatment of metastatic breast cancer, the lack of response or relapse/progression during the course of therapy continue to present a challenge towards deeper understanding of dysregulated signaling pathways in breast cancer. Consequently, there is an unmet medical need for the development of new agents to overcome the resistance to therapy and improve the treatment outcome.
  
  
  METHODS
  In this review, the mechanism of action and the role of intracellular PI3K/AKT/mTOR signaling pathway inhibition in breast cancer patients are described. Everolimus has been approved in combination with exemestane for the treatment of hormone-receptor-positive advanced breast cancer after failure of nonsteroidal aromatase inhibitor therapy. The aim of this paper is to focus on the safety and efficacy of mTOR inhibitors in the treatment of breast cancer. Current strategies of major adverse event management and prevention are delineated.
  
  
  CONCLUSIONS
  Study results demonstrate clearly that the inhibition of the PI3K/AKT/mTOR pathway represents a promising approach to improve the efficacy of other targeted therapies in estrogen receptor-positive breast cancer patients with an acceptable safety profile. Although side effects are not uncommon, these are usually mild to moderate in severity and manageable with supportive care and dose adjustments.
authors.affiliation: a Department of Oncology , Palacký University Medical School & Teaching Hospital , Olomouc , Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Študentová
authors.affiliation: a Department of Oncology , Palacký University Medical School & Teaching Hospital , Olomouc , Czech Republic.
authors.forename: Denisa
authors.initials: D
authors.lastname: Vitásková
authors.affiliation: a Department of Oncology , Palacký University Medical School & Teaching Hospital , Olomouc , Czech Republic.|b Institute of Molecular and Translational Medicine , Palacký University Medical School & Teaching Hospital , Olomouc , Czech Republic.
authors.forename: Bohuslav
authors.initials: B
authors.lastname: Melichar
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: Breast cancer; everolimus; mTOR inhibitors; ridaforolimus; temsirolimus; toxicity