Added Metformin to Systematic Neoadjuvant Chemotherapy in Breast Cancer Patients: Randomized Study from Egypt

Abstract Background: Rational of the neoadjuvant chemotherapy can significantly decrease the size and stage of tumor for breast carcinoma. Studies have demonstrated that there is a greater long-term outcome in patients who reach pathological complete response (pCR) following neoadjuvant therapy. Metformin, a biguanide agent, is used as first-line therapy for the treatment of type II Diabetes. The studies reported that diabetic patients with metformin-administered breast cancer and neoadjuvant chemotherapy had a higher pCR rate than diabetics without Metformin. Aim of Study: To assess the efficacy of incorporating Metformin to standard neoadjuvant chemotherapy in breast cancer patients to increase the rate of pathological complete response (pCR). Patients and Methods: From 1/7/2016 to 1/9/2019, a total of 50 patients were enrolled in the study. Breast cancer patients were equally randomized to receive either standard neoadjuvant AC-Paclitaxel or a similar regimen plus Metformin 500mg twice daily until the time of surgery. For reaction & toxicity, patients were evaluated. Results: Concerning all clinical-pathological variables & biological subtypes, there was no statistically significant difference between both arms. Complete clinical remissions were achieved in 19 patients (76%) and 15 patients (60%) respectively for the investigated group and standard group (p-value 0.4). In the investigated group, 19 patients (76%) were referred to have modified radical mastectomy (MRM) and 6 patients (24%) were referred to have complete breast surgical resection (CBS), while in the standard group, 23 patients (92%) were referred to MRM and 2 patients (8%) were referred to CBS. There was no statistically significant difference between the two types of surgery in the two groups (p-value 0.247). The primary endpoint was the pCR rate in the axilla and breast post operatively. Statistical analysis showed certain trend toward higher rate of pCR with the addition of Metforminin the investigated group compared to the standard group (p-value: 0.08). Uni-variate analysis showed significant correlation with pCR in the 2 groups as regard ER and HER-2/neu positivity, (p-value 0.004).
The Median DFS at 2 years in our study was 93.25%. Kaplan-Meier survival curves' analysis showed no significant difference between both groups with a DFS of 91.25% in the investigated group arm, and 96.25% in the standard group. Conclusion: The addition of metformin to neoadjuvant chemotherapy has a nearby significant impact on pathological complete response (PCR)in female patients with advanced breast cancer with no significant increased toxicity. Further studiesare recommended to highlight the effect of adding metformin to standard neoadjuvant chemotherapy in ER and/or HER2 positive breast cancer patients.