Gene interactions and pathways from curated databases and text-mining
Ann Oncol 2012, PMID: 22112968

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

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

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.

Diseases/Pathways annotated by Medline MESH: Breast Neoplasms, Diabetes Mellitus, Type 2
Document information provided by NCBI PubMed

Text Mining Data

epidermal growth factor receptor → PI3K/AKT/mTOR signaling: " 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 "

epidermal growth factor receptor → PI3K/AKT/mTOR: " 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 "

epidermal growth factor receptor → PI3K/AKT/mTOR: " 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 "

IGF-I receptor → PI3K/AKT/mTOR signaling: " 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 "

IGF-I receptor → PI3K/AKT/mTOR: " 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 "

IGF-I receptor → PI3K/AKT/mTOR: " 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 "

insulin → PI3K/AKT/mTOR signaling: " 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 "

insulin → PI3K/AKT/mTOR: " 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 "

insulin → PI3K/AKT/mTOR: " 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 "

insulin receptor → PI3K/AKT/mTOR signaling: " 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 "

insulin receptor → PI3K/AKT/mTOR: " 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 "

insulin receptor → PI3K/AKT/mTOR: " 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 "

Manually curated Databases

No curated data.