Abstract PO1-05-11: Efficacy of metformin as adjunctive therapy in patients with de novo metastatic breast cancer: a retrospective cohort study
Authors: Chongxi Ren , Jianna Sun , Lingjun Kong , Yu Hongjun 
Published: May 2024

Abstract
Background: Metformin, an oral biguanide used for the treatment of type-2 diabetes mellitus (DM), has been shown in a considerable number of studies to have an anti-tumorigenic impact against breast cancer cells through several mechanisms,thereby improving breast cancer outcomes. However, the impact of metformin treatment on survival outcomes in patients with non-diabetic breast cancer is still under debate, with very few data available regarding metformin administration in de novo metastatic breast cancer (dnMBC). This study was conducted to investigate and evaluate the impact on survival outcomes of patients with dnMBC treated with metformin as adjunctive therapy at our institutes. Methods: All dnMBC women who received chemotherapy-based systemic therapy or combined with metformin administered orally in our hospitals between March 2007 and November 2016 were enrolled in the study. Data were retrospectively extracted from the patients’case records. Data were analyzed according the clinicopathological features and treatment outcomes. All specimens were rechecked for the purpose of the research. Overall survival (OS), as the study endpoint, was defined as the time from pathologically confirmed diagnosis to all-cause death or end of the follow-up time.Kaplan-Meier estimate was used to calculate the survival rates.The difference between metformin and non-metformin groups was compared by the log-rank method.Cox regression analysis (uni-and multivariate analysis) was used to assess the effect of variables on survival outcomes.Analyses were performed by Stata 17 software for windows version. Results: A total of 252 women with dnMBC were included with an average age of 54.41±11.61 years. Among them, 97 patients (including 11 DM patients) received chemotherapy-based systemic therapy plus oral administration of metformin 850-1000mg twice daily (metformin group), and 155 patients received chemotherapy-based systemic therapy (non-metformin group). There was no significant difference in body mass index, age, N-stage, P53 index, ER/PR status, HER-2 expression and initial metastatic sites between metformin group and non-metformin group. But there were differences in T-stage and Ki67 index between the two groups (Table 1). The median follow-up was 70 months.The median OS was 24 months.The 3-year and 5-year OS rates for all patients were 29.8% (95% CI:24.2% to 35.4%) and 11.6% (95% CI:7.5% to 16.7%),respectively; Log-rank test showed that the metformin group had a significant advantage over the non-metformin group in OS rates(p=0.0002).The 3-year and 5-year OS rates in the metformin group were 42.3% (95% CI:32.4% to 51.8%) and 21.2% (95% CI:12.8% to 31.1%), respectively; the same rates for non-metformin group were 21.9% (95% CI: 15.8% to 28.7%) and 5.6% (95% CI: 2.4% to 11.1%), respectively. Results of proportional hazards model, after adjustment for T-stage and Ki67 index, depicted an independent prognostic value of metformin use with multivariate hazard ratio of 0.61 (95% CI: 0.45 to 0.81) for OS compared to non-metformin group (p=0.001).No survival advantage was found for DM patients (0.59;95% CI:0.29 to 1.22; p=0.159). Conclusions: Our data support a favorable outcome for survival associated with metformin use in dnMBC patients. However, the retrospective nature and small sample size of the current study are major limitations to reliable conclusions about metformin's potential to improve OS in patients. Therefore, prospective evidence from phase-3 randomized controlled trials on the feasibility of metformin use in dnMBC is required before its routine use can be recommended. Keywords: Metformin; De novo metastatic breast cancer; Adjunctive therapy; Survival outcomes

Citation Format: Ren Chongxi, Sun Jianna, Kong Lingjun, Hongjun Yu. Efficacy of metformin as adjunctive therapy in patients with de novo metastatic breast cancer: a retrospective cohort study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-05-11.