title: Metformin and thiazolidinediones are associated with improved breast cancer-specific survival of diabetic women with HER2+ breast cancer.
abstract: BACKGROUND
  Insulin/insulin-like growth factor-I (IGF-I) signaling is a mechanism mediating the promoting effect of type 2 diabetes (DM2) on cancer. Human epidermal growth factor receptor (HER2), insulin receptor and IGF-I receptor involve the same PI3K/AKT/mTOR signaling, and different antidiabetic pharmacotherapy may differentially affect this pathway, leading to different prognoses of HER2+ breast cancer.
  
  
  METHODS
  We reviewed 1983 consecutive patients with HER2+ breast cancer treated between 1 January 1998 and 30 September 2010. The overall survival, breast cancer-specific death rate, age, race, nuclear grade, stage, menopausal status, estrogen and progesterone receptor status, body mass index and classes of antidiabetic pharmacotherapy were analyzed.
  
  
  RESULTS
  A Cox regression analysis showed that DM2 [P=0.026, hazard ratio (HR)=1.42, 95 % confidence interval (95 % CI) 1.04-1.94] predicted poor survival of stage≥2 HER2+ breast cancer. In Kaplan-Meier analysis, metformin predicted lengthened survival and so did thiazolidinediones. Analyzing only the diabetics, Cox regression showed that metformin (P=0.041, HR=0.52, 95 % CI 0.28-0.97) and thiazolidinediones (P=0.036; HR=0.41, 95% CI 0.18-0.93) predicted lengthened survival, and competing risk analysis showed that metformin and thiazolidinediones were associated with decreased breast cancer-specific mortality (P=0.023, HR=0.47, 95% CI 0.24-0.90 and P=0.044, HR=0.42, 95 % CI 0.18-0.98, respectively).
  
  
  CONCLUSIONS
  Thiazolidinediones and metformin users are associated with better clinical outcomes than nonusers in diabetics with stage≥2 HER2+ breast cancer. The choice of antidiabetic pharmacotherapy may influence prognosis of this group.
authors: Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: X
authors: X
authors: He
authors: F J
authors: FJ
authors: Esteva
authors: J
authors: J
authors: Ensor
authors: G N
authors: GN
authors: Hortobagyi
authors: M-H
authors: MH
authors: Lee
authors: S-C J
authors: SC
authors: Yeung
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000150:complications / Q000378:metabolism / Q000401:mortality*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D018709:Statistics, Nonparametric; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D018719:Erb-b2 Receptor Tyrosine Kinases; D045162:Thiazolidinediones; C508053:ERBB2 protein, human