Efficacy of Combining Metformin with Neoadjuvant Chemotherapy on Pathologic Response in Non-diabetic Patients with Carcinoma Breast- A Randomized Controlled Trial

Background: In India breast cancer forms the commonest malignancy after cervical cancer in females and is detected in 20 per 1,00,000 women. Metformin acts as oral hypoglycemia drug and anti-tumor drug. Mechanism of action of metformin is to inhibit cellular proliferation as well as to increases pathological Complete Response in breast cancer patients when used in addition to neoadjuvant chemotherapy. Methods: This randomized control trial study was conducted on 54 patients to assess the effect of adding metformin to neoadjuvant chemotherapy in pathologic response in Breast Cancer patients as well as to establish safety and tolerance of metformin as a neoadjuvant drug in Breast cancer and to measure the effect of metformin on sex hormones, tumor and insulin resistance dated from November 2016 to June 2018. Study group received metformin along with neoadjuvant chemotherapy and Control group received neoadjuvant chemotherapy only. In every visit, side effects of metformin were assessed like nausea, vomiting, abdominal discomfort, dizziness. Pre NACT-BMI and Post NACT- BMI were calculated and differences were assessed. Any post-operative complication was looked for post-surgery. Data was analysed by SPSS version 19. Results: Our study showed that DHEAS level decreased by 5.65 in study group while the fall in DHEAS in non-metformin arm was 2.1. 7.1% of participants in metformin group showed complete response, 78.6% participants showed partial response and 14.3% had progressive disease. In non-metformin group, complete, partial response and progressive disease were seen in 40.0%, 60.0% and 0.0% respectively. Patient in control group had higher complete response. However, the difference in pathologic complete response between metformin and non-metformin group has no statistical significance (p= 0.057). Conclusion: Our study supports the view that patient without insulin resistance treated with NACT alone has higher pathologic complete response than the patient treated with NACT with metformin. However, sample size of present study is small to support the results.