Metformin Use and Risk of Breast Cancer-Related Lymphedema: A Retrospective Analysis.

Background: Over 30% of breast cancer patients develop lymphedema following axillary lymph node dissection (ALND), significantly impacting their quality of life. Comorbid conditions like 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.

Methods: We conducted a retrospective analysis of breast cancer patients at Memorial Sloan Kettering Cancer Center who underwent ALND from January 2004 through December 2022 (4,882 patients overall). We stratified patients according to if they were diagnosed with DM at the time of surgery, and if so, if 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. While having diabetes at the time of ALND was a significant risk factor for lymphedema on univariable (HR: 1.38; 95% CI: 1.14, 1.66; P < .001) and multivariable (HR: 1.55; 95% CI: 1.19, 2.02; P = .001) analysis, metformin treatment was associated with a significant decrease in lymphedema risk (univariable HR: 0.66; 95% CI: 0.46, 0.94; P = .023; multivariable HR: 0.62; 95% CI: 0.43, 0.89; P = .010).

Conclusions: Diabetic breast cancer patients 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.