The Effect of Metformin When Combined With Neoadjuvant Chemotherapy in Breast Cancer Patients

Abstract

BackgroundMetformin has been used to treat type 2 Diabetes Mellitus since long time. It has two proposed anti-neoplastic mechanisms, direct (insulin-independent) and indirect (insulin-dependent) actions. PurposeTo assess the effect of Metformin on pathological response when combined with neoadjuvant chemotherapy in breast cancer. Material and MethodsA prospective study included stage II, III non-diabetic breast cancer patients who received neoadjuvant chemotherapy in our center during the period from May 2017 to March 2019. 59 patients met our inclusion criteria and completed the study, 27 patients received 850mg Metformin every 12 hrs with chemotherapy (group A), 32 patients received chemotherapy without Metformin (group B). Pathological response was assessed by Chevallier classification and residual cancer burden score (RCB). ResultsBoth groups were well balanced regarding base line characteristics. The results of our study showed that the rate of pathological complete response (pCR) was 14.8% in group (A) vs. 6.3% in group (B) with a P-value of 0.39. RCB class 3 was 40.7% in group (A) Vs. 68.8% in group (B) which was statistically significant with a (P-value of 0.031). Patients with triple-positive histology who had RCB class 3 were only (14.3%) in group (A) versus (60%) in group B. Patients with body mass index (BMI) ≥25 who had RCB 3 were 40% and 66.7% in group (A) and (B) respectively. ConclusionMetformin may increase the pCR especially in patients with BMI≥25 and patients with triple-positive histology, a larger phase III study is needed to confirm this finding.

Tumour, whole‐blood, plasma and tissue concentrations of metformin in lung cancer patients

“…23 El-Khayat et al found that the addition of metformin significantly increased the rate of pathologic complete response to neoadjuvant chemotherapy in breast cancer. 24 In contrast, Lopez-Bonet et al observed that the addition of metformin did not alter the pathologic complete response rate of human epidermal growth factor receptor 2-positive breast tumours treated with neoadjuvant trastuzumab, anthracycline and taxane. 25 A study in ovarian cancer patients revealed that metformin increased the proportion of cancer cells that co-expressed the stem cell-like markers aldehyde dehydrogenase (ALDH) and CD133.…”

“…For example, Yee et al reported that the addition of metformin modestly increased the pathologic complete response rate to neoadjuvant ganitumab in breast cancer patients 23 . El‐Khayat et al found that the addition of metformin significantly increased the rate of pathologic complete response to neoadjuvant chemotherapy in breast cancer 24 . In contrast, Lopez‐Bonet et al observed that the addition of metformin did not alter the pathologic complete response rate of human epidermal growth factor receptor 2‐positive breast tumours treated with neoadjuvant trastuzumab, anthracycline and taxane 25 .…”