The Effect of Neoadjuvant Chemotherapy on Breast Cancer-Related Lymphedema: A Prospective Clinical Trial

Background: Breast cancer-related lymphedema (BCRL) is a frequent complication that can impair the quality of life of survivors. While the effect of surgery and radiotherapy on lymphedema has been well established, the independent impact of neoadjuvant chemotherapy (NACT) on extracellular fluid remains unclear. Methods: In this prospective clinical study, 111 patients with breast cancer scheduled for NACT were evaluated before and after chemotherapy. Arm circumferences and bioimpedance spectroscopy (BIS, L-Dex U400 ® ) were performed pre- and post-NACT to assess extracellular fluid changes. A ≥6.5-unit increase in L-Dex was considered significant. Demographic, clinical, and pathological variables were analyzed using univariate and multivariate logistic regression. Results: Extracellular fluid increase was detected in 18 patients (16.2%) after NACT, with no clinical lymphedema observed. In multivariate analysis, age ≥55 years (OR 4.47, 95% CI: 1.35–14.89; p = 0.015) and higher clinical N stage (OR 2.26, 95% CI: 1.16–4.43; p = 0.017) were independent predictors of extracellular fluid increase, whereas hormone receptor positivity was protective (OR 0.23, 95% CI: 0.07–0.72; p = 0.012). Conclusions: NACT may contribute to subclinical extracellular fluid accumulation, particularly in older patients, those with advanced nodal disease, and those lacking hormone receptor positivity. Early BIS monitoring during chemotherapy may facilitate the detection of subclinical extracellular fluid changes and identify patients who may warrant closer surveillance for subsequent lymphedema.