title: Metformin is associated with improved survival in endometrial cancer.
abstract: OBJECTIVE
  Preclinical evidence suggests that metformin exhibits anti-tumorigenic effects in endometrial cancer. We sought to investigate the association of metformin on endometrial cancer outcomes.
  
  
  METHODS
  A multi-institutional IRB-approved retrospective cohort analysis was conducted comparing endometrial cancer patients with diabetes mellitus who used metformin (based on medication review at the time of diagnosis) to those who did not use metformin from 2005 to 2010. Metformin use on treatment related outcomes (TTR: time to recurrence; RFS: recurrence free survival; OS: overall survival) were evaluated using univariate and multivariate modeling.
  
  
  RESULTS
  24% (363/1495) endometrial cancer patients were diabetic, of whom 54% used metformin. Metformin users were younger and heavier than non-users, though nearly all were postmenopausal and obese. 75% of both groups had endometrioid histology. Stage, grade, and adjuvant therapy distributions were similar. Metformin users had improved RFS and OS. Non-metformin users had 1.8 times worse RFS (95% CI: 1.1-2.9, p = 0.02) and 2.3 times worse OS (95% CI: 1.3-4.2, p = 0.005) after adjusting for age, stage, grade, histology and adjuvant treatment. Metformin use was not associated with TTR.
  
  
  CONCLUSIONS
  Metformin use was associated with improved RFS and OS but not TTR, most likely due to improving all-cause mortality. Its role in modifying cancer recurrence remains unclear. Prospective studies that capture metformin exposure prior to, during and post endometrial cancer treatment may help define the role of metformin upon cancer specific and overall health outcomes.
authors.affiliation: University of Pennsylvania, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, USA.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Ko
authors.affiliation: Department of Obstetrics and Gynecology, Duke University, USA.
authors.forename: Paige
authors.initials: P
authors.lastname: Walter
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Jackson
authors.affiliation: Department of Obstetrics and Gynecologic Oncology, University of North Carolina at Chapel Hill, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Clark
authors.affiliation: Department of Obstetrics and Gynecologic Oncology, University of North Carolina at Chapel Hill, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Franasiak
authors.affiliation: Department of Obstetrics and Gynecology, Duke University, USA.
authors.forename: Corey
authors.initials: C
authors.lastname: Bolac
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University, USA.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Havrilesky
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University, USA.
authors.forename: Angeles Alvarez
authors.initials: AA
authors.lastname: Secord
authors.affiliation: University of North Carolina Lineberger Comprehensive Cancer Center, USA.
authors.forename: Dominic T
authors.initials: DT
authors.lastname: Moore
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, USA; University of North Carolina Lineberger Comprehensive Cancer Center, USA.
authors.forename: Paola A
authors.initials: PA
authors.lastname: Gehrig
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, USA; University of North Carolina Lineberger Comprehensive Cancer Center, USA. Electronic address: vbae@unch.unc.edu.
authors.forename: Victoria
authors.initials: V
authors.lastname: Bae-Jump
mesh_terms: D000368:Aged; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000188:drug therapy; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
keywords: Diabetes; Endometrial cancer; Metformin; Obesity