Association between neoadjuvant and adjuvant chemotherapy and severity of breast cancer-related lymphedema following axillary lymph node dissection

Breast Cancer-Related Lymphedema (BCRL) is one of the most frequent complication after axillary lymph node dissection (ALND). The aim of this study was to evaluate the severity of BCRL in patients with established BCRL following ALND, focusing on the timing of chemotherapy relative to the surgery (neoadjuvant vs. adjuvant), in the presence of other factors affecting BCRL. This cross-sectional study included 664 breast cancer patients with established BCRL following ALND who were referred to two physiotherapy centers. BCRL was determined by measurements of arm circumferences. Volume differential (VD) between the two arms was classified as 5–10%, 11–30%, and > 30%. Overall, 41.9% ( n = 278), 36.9% ( n = 245) and 21.2% ( n = 141) of patients had severe, moderate and mild BCRL, respectively. Although VD was higher in the adjuvant than the neoadjuvant group, there were no statistically significant differences between two groups (30.92 ± 23.20 vs. 26.32 ± 17.42, Z=-1.59, p = 0.11). Furthermore, the median interval between surgery and lymphedema diagnosis was longer in the adjuvant group, with a median time of 19 months compared to 12 months (Z=-7.23, p < 0.001). Multivariable logistic regression analysis showed a lower odds of severe BCRL in the neoadjuvant group compared to adjuvant (OR = 0.36, 95%CI = 0.14–0.94, p = 0.04). Age, radiotherapy, and the number of involved lymph nodes were significantly associated with high severity of BCRL. Additionally, the rate of severe lymphedema in patients who adhered to preventive measures was significantly lower than in those who did not (27.9% vs. 53%, p < 0.001). Among breast cancer patients with established BCRL following ALND, those who received neoadjuvant chemotherapy were less likely to experience severe lymphedema than patients treated with adjuvant chemotherapy. Older age, radiotherapy, and a greater number of involved nodes were identified as factors linked to increased lymphedema severity. Conversely, adherence to preventive measures was related to a lower likelihood of severe BCRL. Further prospective studies are needed to confirm these findings and clarify the underlying mechanisms.