title: Bone effects of mammalian target of rapamycin (mTOR) inhibition with everolimus.
abstract: Patients with breast cancer face substantial challenges to bone health from bone metastases, as well as from chemotherapy and endocrine therapies that generally elicit disease control at the cost of increased bone turnover. Consequently, maintaining bone health is of critical importance for these patients. Recently reported results from BOLERO-2 showed significant clinical benefits with adding everolimus to exemestane therapy in postmenopausal women with estrogen-receptor-positive breast cancer recurring or progressing despite nonsteroidal aromatase inhibitor therapy. Moreover, exploratory analyses from BOLERO-2 showed that adding everolimus may have beneficial effects on bone turnover and progressive disease in bone in this patient population. These results are supported by preclinical studies in which mTOR inhibition was associated with decreased osteoclast survival and activity. Thus, everolimus therapy may be able to ameliorate the negative effects of estrogen suppression on bone health. This review discusses the effects of mTOR inhibition on bone health during endocrine therapy.
authors.affiliation: Department of Gynecology, Philipps-University of Marburg, Marburg, Germany. hadji@med.uni-marburg.de
authors.forename: Peyman
authors.initials: P
authors.lastname: Hadji
authors.forename: Robert
authors.initials: R
authors.lastname: Coleman
authors.forename: Michael
authors.initials: M
authors.lastname: Gnant
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000068338:Everolimus; D005260:Female; D006801:Humans; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000068338:Everolimus; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: Aromatase inhibitors; Bone; Breast cancer; Everolimus; Postmenopausal women; mTOR