303P - Metformin and response to neoadjuvant chemotherapy in patients with breast cancer

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Breast Cancer
Presenter Mohammed Ghareeb
Citation Annals of Oncology (2016) 27 (6): 68-99. 10.1093/annonc/mdw365
Authors M. Ghareeb1, H. Naser2, M. El-Gammal2, A. Zeeneldin2, A. Bahnacy3, H. Khaled2
  • 1Medical Oncology, National Cancer Institute, 11796 - Cairo/EG
  • 2Medical Oncology, National Cancer Institute, Cairo/EG
  • 3Pathology, National Cancer Institute, Cairo/EG



Breast cancer is the most frequently diagnosed malignancy and is a leading cause of cancer death in women worldwide. Neoadjuvant chemotherapy for breast cancer has been established as an effective therapeutic approach for advanced non metastatic-breast cancer. Metformin, an oral hypoglycemic drug with well-established side effect and safety profiles, has been widely studied for its anti-tumor activities in a number of cancers, including breast cancer.


This study included 76 female non-diabetic patients with IDC who were eligible for neoadjuvant chemotherapy. They underwent clinical examination, bilateral mammography and ultrasound, and other standard radiologic modalities and they received anthracycline-based regimen (with or without Taxanes according to clinical response) with metformin 500mg, twice daily till time of surgery. After surgery, pathological response (by both Miller and Satellof grading systems) and RNA expression levels of p53 pathway, and the PI3K/AKT/m-TOR pathway were done on tissues


The mean age was 44.3 years. The mean BMI was 32.8 Kg/m2 and 37.3 Kg/m2 in good responders and poor responders respectively (p value 0.042). Grade III pathology, Her2overexpression, T2-3 tumor, stage II and smaller mammographic tumor size were predictors of better pathological response. Obese patients had better DFS than normal-overweight group of patients (p value 0.001). Significant overexpression of AMPK, LKB1, TSC1/2, OCT1, PKA, APAF1, P53, P21, RPRM., PIDD,FADD and CHEK1/2 and reduced expression of m-TOR, CYCLIN D-1,VEGF, CDK-4, CDK-1,IGF, NFKB and AKT among responders suggesting action of metformin can be through AMPK activation and subsequent stimulation of p53, inhibition of mTOR, reduced expression of IGF1, stimulation of apoptotic pathways


Obese group of patients had significantly better DFS when compared to normal-overweight group of patients, this could be explained by adding Metformin to neoadjuvant chemotherapy but further studies with larger number of patients and longer follow up is warranted. Also further efforts are needed for establishing antineoplastic molecular pathway for metformin

Clinical trial identification

Legal entity responsible for the study

National Cancer Institute, Egypt


National Cancer Institute, Egypt


All authors have declared no conflicts of interest.