Abstract
BACKGROUND: More than 30% of patients with breast cancer develop lymphedema after axillary lymph node dissection (ALND), significantly impacting their quality of life. Comorbid conditions such as diabetes mellitus (DM), which contribute to endothelial dysfunction and inflammation, may also affect lymphatic endothelium. Preclinical studies suggest that metformin, a common DM treatment, may reduce lymphedema risk. STUDY DESIGN: We conducted a retrospective analysis of patients with breast cancer at Memorial Sloan Kettering Cancer Center who underwent ALND from January 2004 to December 2022 (4,882 patients overall). We stratified patients according to whether they were diagnosed with DM at the time of surgery, and if so, whether they were receiving metformin. We also conducted univariable and multivariable analyses of patient demographics for the overall cohort and the metformin vs no-metformin DM subgroups. RESULTS: Of the 407 patients with diabetes at the time of ALND, 250 (61%) were receiving metformin and 157 (39%) were not. Although having diabetes at the time of ALND was a significant risk factor for lymphedema on univariable (hazard ratio [HR] 1.38, 95% CI 1.14 to 1.66, p < 0.001) and multivariable (HR 1.55, 95% CI 1.19 to 2.02, p = 0.001) analysis, metformin treatment was associated with a significant decrease in lymphedema risk (univariable HR 0.66, 95% CI 0.46 to 0.94, p = 0.023; multivariable HR 0.62, 95% CI 0.43 to 0.89, p = 0.010). CONCLUSIONS: Patients with diabetic breast cancer have a significantly increased risk of developing lymphedema after ALND; however, those using metformin at the time of surgery had a lower incidence compared to non-users.