Investigating the relationship between insulin use and all-cause mortality, breast cancer mortality, and recurrence risk in diabetic patients with breast cancer: A comprehensive systematic review and meta-analysis

Abstract

Background The co-occurrence of breast cancer and diabetes presents complex clinical challenges, as each condition may influence the progression and management of the other, potentially worsening patient outcomes. This study aims to examine the association between insulin use and the risks of all-cause mortality, breast cancer-specific mortality, and recurrence in diabetic patients with breast cancer. Methods A systematic review and meta-analysis were conducted using studies identified from multiple databases, including Web of Science, Scopus, PubMed, Cochrane, Google Scholar, and Embase. The meta-analysis approach was used to estimate the relative risk (RR) of the relationship between insulin use and the risks of all-cause mortality, breast cancer-specific mortality, and recurrence in diabetic patients with breast cancer. Heterogeneity among studies was assessed using statistical tests such as the Chi-square test, I-2, and forest plots. Meta-regression and sensitivity analyses were performed to explore sources of heterogeneity. The quality of the included studies was assessed using the Newcastle-Ottawa Scale checklist. Data were analyzed using Stata version 17 (Stata Corp, College Station, Texas). Results Data from 22 studies conducted between 2002 and 2023, with a total of 159,674 participants, were analyzed. Nineteen studies were rated as high quality, and three as moderate quality. Diabetic patients with breast cancer who received insulin had a 1.65 (95 CI: 1.36-2.02; P < 0.001; I-2 = 89.7) times higher risk of overall mortality compared to those who did not use insulin. Meta-regression revealed that sample size and study quality were significant contributors to heterogeneity (P <= 0.10). Furthermore, insulin use was associated with a 1.22 (95 CI: 1.05-1.42; P = 0.009; I-2 = 37.9) times higher risk of breast cancer-specific mortality. For breast cancer recurrence, insulin use was associated with a 1.45 (95 CI: 1.19-1.77; P < 0.001; I-2 = 3.4) times higher risk. Sensitivity analysis confirmed the stability of the results across all outcomes. Conclusion This meta-analysis provides strong evidence that insulin use in diabetic patients with breast cancer is associated with increased risks of overall mortality, breast cancer-specific mortality, and recurrence. These findings underscore the need for careful consideration of insulin therapy in this patient population.