title: Targeting the mammalian target of rapamycin pathway with everolimus: implications for the management of metastatic breast cancer.
abstract: The inhibitors of mammalian target of rapamycin (mTOR) have documented antitumor activity via disruption of various signaling pathways leading to impaired cellular growth, proliferation, and survival. In preclinical studies, mTOR inhibitors use in combination with hormonal therapy has shown promising results in overcoming endocrine resistance in breast cancer cells. The role of everolimus in breast cancer was established in the Breast Cancer Trial of Oral Everolimus-2 (BOLERO-2) trial in combination with exemestane for patients with advanced metastatic hormone receptor-positive (HR+) breast cancer, who relapsed after initial hormonal manipulation. The study met its primary endpoint of significant improvement in progression free survival (PFS) with a median time to progression of 6.9 months in the combination group versus 2.8 months in exemestane group. Favorable improvements in PFS were reported across all patient subgroups regardless of age, Eastern Cooperative Oncology Group performance status, number of prior therapies, and presence of visceral metastases. Adverse events were mostly mild to moderate in severity and consistent with the known safety profile of everolimus. Major toxicities reported include stomatitis, non-infectious pneumonitis, and hyperglycemia. The purpose of this review is to discuss the role of everolimus as a valuable component in advanced metastatic breast cancer and delineate current strategies to prevent and manage the most common toxicities associated with this combination regimen.
authors: Department of Pharmacy, Singapore General Hospital, Outram Rd Singapore, 169680 Singapore.
authors: Vin Cci
authors: VC
authors: Ng
authors: Department of Pharmacy, Singapore General Hospital, Outram Rd Singapore, 169680 Singapore Cancer Center, University of Illinois at Chicago, Chicago, IL, USA.
authors: Jeremy J
authors: JJ
authors: Johnson
authors: Department of Pharmacy, Singapore General Hospital, Outram Rd Singapore, 169680 Singapore Cancer Center, University of Illinois at Chicago, Chicago, IL, USA scuell1@uic.edu.
authors: Sandra
authors: S
authors: Cuellar
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000068338:Everolimus / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects* / Q000235:genetics
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: Mammalian target of rapamycin inhibitor; everolimus; management of adverse events; metastatic breast cancer; supportive care