title: [Exemestane-everolimus in HER2-negative, hormonal receptor-positive, post-menopausal metastatic breast cancer with resistance to non-steroidal aromatase inhibitor: a new option].
abstract: Phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is commonly deregulated in breast cancer and has been involved in resistance to endocrine therapy. In the BOLERO-2 study, the addition of everolimus, a selective inhibitor of mTOR protein, to exemestane was associated with a significant improvement in progression-free survival, compared to exemestane plus placebo, in patients with hormone receptor-positive, HER2-negative metastatic breast cancer, and resistant to non-steroidal aromatase inhibitor therapy. However, adverse events and treatment stops were more often observed with the combination therapy, suggesting the need for a careful benefit/risk evaluation before initiating this new combination. This review aims at synthesizing the biological basis of the everolimus-exemestane association, presenting the main validated and ongoing therapeutic trials, interests and limits, as well as the multiple potential therapeutic perspectives.
authors.affiliation: Institut Paoli-Calmettes, Oncologie médicale, 232, boulevard de Sainte-Marguerite, 13008 Marseille, France, Inserm U1068-CNRS U7258, Université Aix-Marseille, Centre de recherche en cancérologie de Marseille, Faculté des sciences de Lumigny, 163, avenue de Luminy, 13009 Marseille, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Gilabert
authors.affiliation: Institut Paoli-Calmettes, Oncologie médicale, 232, boulevard de Sainte-Marguerite, 13008 Marseille, France, Inserm U1068-CNRS U7258, Université Aix-Marseille, Centre de recherche en cancérologie de Marseille, Faculté des sciences de Lumigny, 163, avenue de Luminy, 13009 Marseille, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Launay
authors.affiliation: Institut Paoli-Calmettes, Oncologie médicale, 232, boulevard de Sainte-Marguerite, 13008 Marseille, France, Inserm U1068-CNRS U7258, Université Aix-Marseille, Centre de recherche en cancérologie de Marseille, Faculté des sciences de Lumigny, 163, avenue de Luminy, 13009 Marseille, France, Aix-Marseille Université, 13001 Marseille, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Gonçalves
mesh_terms: D000730:Androstadienes / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D000068338:Everolimus; D005260:Female; D006801:Humans; D009363:Neoplasm Proteins / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D016032:Randomized Controlled Trials as Topic; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D000730:Androstadienes; D047072:Aromatase Inhibitors; D000068338:Everolimus; D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human; C056516:exemestane
keywords: breast cancer; everolimus; exemestane; hormonoresistance; mTOR; metastatic