Metformin and thiazolidinediones are associated with improved breast cancer-specific survival of diabetic women with HER2+ breast cancer

X. He, F. J. Esteva, J. Ensor, G. N. Hortobagyi, M. H. Lee, S. C.J. Yeung

Research output: Contribution to journalArticle

143 Scopus citations

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.

Original languageEnglish (US)
Article numbermdr534
Pages (from-to)1771-1780
Number of pages10
JournalAnnals of Oncology
Volume23
Issue number7
DOIs
StatePublished - Jul 2012

Keywords

  • Breast cancer-specific mortality
  • HER2-positive breast cancer
  • Insulin
  • Metformin
  • Secretagogues
  • Thiazolidinediones

ASJC Scopus subject areas

  • Hematology
  • Oncology

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