Neoadjuvant Metformin Added to Systemic Therapy Increases Pathological Complete Response in Breast Cancer: A Cross-sectional Study, Mexico Hospital, Costa Rica

Abstract

Background: Metformin shows anti-proliferative effect on tumor cells. We studied the effect of metformin on achieving complete pathological response (pCR) in breast cancer patients receiving neoadjuvant therapy in a Latin American population. Methods: We conducted a cross-sectional study in Mexico Hospital, Costa Rica, from January 2007 to December 2015. Women with early-stage or locally advanced breast cancer receiving neoadjuvant systemic treatment were recruited for the study. Univariate and multivariate models were used to compare the pCR rate with metformin plus standard therapy versus standard treatment alone. Results: Of 53 included women with early-stage or locally advanced breast cancer were included, 14 received metformin with systemic therapy, and 39 had systemic therapy alone. Only 15% of the patients had diabetes mellitus. The pCR rate was in the metformin group was 64.3% compared with 23.1% in the systemic therapy-alone group (OR: 6.0, 95% CI: 1.60–22.53, P= 0.008). This finding was confirmed after adjustment for potential confounders, suggesting that the use of metformin increased the pCR likelihood regardless of breast cancer subtype (adjusted OR: 5.56, 95% CI: 1.27–24.3, P = 0.02). There was a trend of achieving pCR in patients with Ki-67 > 55%. However, it did not reach statistical significance when metformin was added, suggesting that probably a high Ki-67 level in the presence of metformin is not a predictor factor of pCR. Conclusion: This is the first study conducted in a Latin American population showing that metformin with systemic therapy increases pCR regardless of the intrinsic molecular subtype or Ki-67 levels. These findings encourage prospective studies to evaluate the role of neoadjuvant metformin in this population.