Risk Factors Associated with Breast Cancer-Related Lymphedema: A Systematic Review and Meta-Analysis

Background: Lymphedema is a chronic, progressive condition that commonly occurs after treatment for breast cancer. Therefore, this study aimed to assess the incidence and risk factors of breast cancer-related lymphedema (BCRL). Methods: PubMed, Web of Science, Embase, MEDLINE, CNKl, Wang Fang DATA, Vip Database, and SinoMed were searched from January 2000 to January 2022. Risk of bias was assessed using the Newcastle-Ottawa Scale. Estimates of pooled incidence and risk factors estimates were calculated with 95% confidence intervals (CI), with sub-group analyses according to country, study design, population characteristics, the definition of lymphedema, and risk of bias. Heterogeneity was measured using I2 and publication bias was analyzed by funnel plot. Results: 34 studies comprising 23,988 participants were included in this study, with a follow-up period ranging from 1 to 10.2 years. The estimated pooled cumulative incidence at 1,2,3,5 years post-operative for patients respectively was 20%, 17%, 18% and 23%. Factors like: stage III cancer (RR: 1.34; 95% Cl: 1.17-1.52), age≥50 (RR: 1.47; 95% Cl: 1.23-1.76), BMI ≥25 (RR: 2.09; 95% Cl: 1.85-2.36), ALND (RR: 2.72; 95% Cl: 1.89-3.92), axillary radiotherapy (RR: 2.19; 95% Cl: 1.64-2.92), Neo-adjuvant chemotherapy (RR: 1.61; 95% Cl: 1.08-2.39), adjuvant taxane-based chemotherapy (RR: 1.65; 95% Cl: 1.25-2.19) and postoperative wound complications (RR: 1.66; 95% Cl: 1.13- 2.43) were significantly associated with BCRL. Conclusions: Our analyses suggest that BCRL risk is significantly associated with cancer stage, age, BMI, ALND, radiotherapy, chemotherapy, and postoperative wound complications.