ABSTRACT
Recent population studies provide clues that the use of metformin may be associated with reduced incidence and improved prognosis of breast cancer. This drug is widely used in the treatment of type 2 diabetes, where it is often referred to as an 'insulin sensitizer' because it not only lowers blood glucose, but also reduces the hyperinsulinemia associated with insulin resistance, Metformin inhibits the growth of cancer cells in vitro and tumors in vivo. However, there are little clinical data to support this. The aim of the study was to determine whether metformin use was associated with better clinical outcomes in diabetic patients with breast cancer receiving adjuvant chemotherapy. In this retrospective study, we reviewed the records of 460 consecutive patients with pathologically proved stage l-lll breast cancer. These patients received adjuvant chemotherapy during the period from January 2008 to December 2008. Patients were compared by groups that consisted of 25 diabetic patients taking metformin, 14 diabetic patients not taking metformin, and 400 nondiabetic patients. In Kaplan-Meier analysis, metformin use during adjuvant chemotherapy significantly improved survival outcomes in diabetic patients' disease-free survival and overall survival. In multivariate Cox regression, metformin usage was a predictive factor that decreased the risk for breast cancer mortality. There is an association between metformin use and better survival outcome in diabetic breast cancer patients who received metformin during adjuvant chemotherapy. The choice of antidiabetic pharmacotherapy may influence prognosis of this group
ABSTRACT
The search for a simple, sensitive test to reliably determine prognosis and predict response to therapy in patients with cancer is an important area of translational research. The Her-2/neu oncogene and its receptor protein overexpression are indicators of more aggressive form of breast cancer. Her-2/neu overexpression was involved in cell differentiation, proliferation, migration and carcinogenesis. The main target of this study is to investigate the possible correlation between tissue Her-2/neu, serum Her-2/neu extracellular domain [ECD] and MMP-9. The impact of the assayed parameters on the disease free survival [DFS] in breast cancer patients will also investigated after one year of follow up. Serum was collected from 33 breast cancer patients and 10 healthy volunteers. Serum Her-2/neu ECD was detected by enzyme linked Immunosorbent assay [ELISA] and serum MMP-9 was detected by enzyme Immunoassay [EIA]. Patients were reevaluated after one year of follow up to detect disease relapse. Positive correlation between expression of Her-2/neu in the primary tumor tissue and the circulating serum Her-2/neu ECD was detected. Serum Her-2/neu ECD was more sensitive in predicting disease free survival than tissue Her-2/neu. Positive correlation between expression of Her-2/neu in the primary tumor and serum MMP-9 was also observed. In contrast, negative correlation between circulating serum Her-2/neu ECD and serum MMP-9 was detected in patients with tissue positive Her-2/neu. We also observed that MMP-9 was a good monitoring factor for the chemotherapy response. We concluded that serum Her-2/neu ECD might be a good prognostic parameter in addition to tissue Her-2/neu and MMP-9 might be the member of MMPs family that responsible for the shedding of the ECD of Her-2/neu receptor