title: mTOR inhibitors: changing landscape of endocrine-resistant breast cancer.
abstract: Most breast cancer (BC) patients have tumors that express hormone receptors (HRs). Although endocrine therapy, such as aromatase inhibitors, is very effective, most patients with metastatic HR-positive (HR(+)) BC become resistant to endocrine therapy at some point in their treatment and subsequently require chemotherapy. The PI3K/mTOR pathway is often upregulated in endocrine-resistant BC patients and, therefore, has been one of the targets for development of new agents. Recently, a Phase III trial (BOLERO-2) in aromatase inhibitor-resistant BC patients showed a significant improvement in time to progression with the combination of everolimus and exemestane compared with exemestane alone, confirming the importance of the PI3K/mTOR pathway in endocrine-resistant BC. Side effects from mTOR inhibitors are manageable, but early detection and proactive management are required to ensure patients' safety, compliance and continuity of treatment. Thus, mTOR inhibitors offer a new hope and promise for patients with HR(+) BC.
authors.affiliation: Department of Medicine, University of Maryland, Greenebaum Cancer Center, Baltimore, MD, USA.
authors.forename: Saranya
authors.initials: S
authors.lastname: Chumsri
authors.forename: Gauri
authors.initials: G
authors.lastname: Sabnis
authors.forename: Katherine
authors.initials: K
authors.lastname: Tkaczuk
authors.forename: Angela
authors.initials: A
authors.lastname: Brodie
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D000068338:Everolimus; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use; D020123:Sirolimus / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D018931:Antineoplastic Agents, Hormonal; D007211:Indoles; D011687:Purines; C401859:temsirolimus; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; C572919:PP242; D020123:Sirolimus