title: Role of inhibitors of mammalian target of rapamycin in the treatment of luminal breast cancer.
abstract: Approximately 75% of patients with breast cancer present hormone receptor-positive tumors. This subtype of breast cancer initially shows a high overall response rate to hormonal treatments. However, resistance eventually develops, resulting in tumor progression. The PI3K/Akt/mTOR pathway regulates several cellular functions in cancer such as cell growth, survival, and proliferation. In addition, a high activation level of the PI3K/Akt/mTOR pathway is related to resistance to conventional chemotherapy and hormone therapy. The mTOR inhibitor everolimus, in combination with hormonal treatments, has led to excellent results in progression-free survival in patients with metastatic breast cancer resistant to hormone therapies. Therefore, everolimus has entered the National Comprehensive Cancer Network (NCCN) guidelines 2012 and its combination with exemestane was approved recently by the US Food and Drug Administration and the European Medicines Agency. This is the first time that a drug will have been approved for the restoration of hormone sensitivity in breast cancer.
authors.affiliation: Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain. eva.ciruelos@gmail.com
authors.forename: Eva
authors.initials: E
authors.lastname: Ciruelos
authors.forename: Hernán
authors.initials: H
authors.lastname: Cortes-Funes
authors.forename: Ismael
authors.initials: I
authors.lastname: Ghanem
authors.forename: Luis
authors.initials: L
authors.lastname: Manso
authors.forename: Carlos
authors.initials: C
authors.lastname: Arteaga
mesh_terms: D000730:Androstadienes / Q000008:administration & dosage; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D000068338:Everolimus; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D047072:Aromatase Inhibitors; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; C056516:exemestane; D020123:Sirolimus