title: mTOR inhibitors in the management of hormone receptor-positive breast cancer: the latest evidence and future directions.
abstract: BACKGROUND
  There is an unmet therapeutic need in endocrine-resistant, hormone receptor (HR)-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (BC). Preclinical studies support the hypothesis that the mammalian target of rapamycin (mTOR) inhibition could potentially overcome resistance to endocrine therapy.
  
  
  METHODS
  A literature review regarding BC and mTOR inhibitors was undertaken. The reference lists from retrieved manuscripts were reviewed to identify further studies.
  
  
  RESULTS
  Phase II studies have reported that the combination of mTOR inhibitors with endocrine therapy shows efficacy in patients with advanced disease that progressed after treatment with aromatase inhibitors. The recent findings of the phase III BOLERO-2 confirmed that everolimus in combination with exemestane significantly improved progression-free survival and response rate, with a manageable safety profile.
  
  
  CONCLUSIONS
  The addition of everolimus to exemestane for women with HR-positive metastatic BC is now considered a new therapeutic strategy. However, a word of caution should be added regarding toxic effects, which might limit practical use and compliance. It is essential that clinicians are educated about key recommendations for toxicity management and specific guideline dose modifications. Additional research efforts with the addition of these compounds in the early-stage setting is greatly needed to improve the survival of patients with HR-positive BC.
authors.affiliation: Department of Medical Oncology, Instituto Nacional de Cancerologia, Mexico DF, Mexico.
authors.forename: C
authors.initials: C
authors.lastname: Villarreal-Garza
authors.affiliation: Breast Cancer Unit, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Cortes
authors.affiliation: Breast Cancer Unit, Department of Medical Oncology, University Paris XI and Institut Gustave Roussy, Villejuif, France.
authors.forename: F
authors.initials: F
authors.lastname: Andre
authors.affiliation: Department of Medical Oncology, Sunnybrook Odette Cancer Centre, Toronto, Canada. Electronic address: Sunil.verma@sunnybrook.ca.
authors.forename: S
authors.initials: S
authors.lastname: Verma
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D020847:Estrogen Receptor Modulators; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human