Factors Associated With Lymphedema in Women With Node-Positive Breast Cancer Treated With Neoadjuvant Chemotherapy and Axillary Dissection

Abstract

This cohort study examines factors associated with lymphedema after neoadjuvant chemotherapy and axillary lymph node dissection in women with node-positive breast cancer. What factors are associated with breast cancer–related lymphedema after neoadjuvant chemotherapy and axillary dissection? In this cohort study of 486 patients with breast cancer, increasing body mass index and neoadjuvant chemotherapy duration of 144 days or longer were associated with lymphedema symptoms, neoadjuvant chemotherapy duration of 144 days or longer was associated with a 20% limb volume increase, and removal of 30 nodes or more and higher number of positive nodes were associated with a 10% limb volume increase. The findings suggest that patients with longer duration of neoadjuvant chemotherapy or obesity have higher lymphedema risk and may benefit from enhanced prospective lymphedema surveillance. Most lymphedema studies include a heterogeneous population and focus on patients treated with adjuvant chemotherapy. To examine factors associated with lymphedema after neoadjuvant chemotherapy (NAC) and axillary lymph node dissection in women with node-positive breast cancer. This cohort study included data from 701 women 18 years or older with cT0-T4N1-2M0 breast cancer with documented axillary nodal metastasis at diagnosis who were enrolled in the American College of Surgeons Oncology Group Z1071 (Alliance for Clinical Trials in Oncology) trial, which took place from January 1, 2009, to December 31, 2012. Data analysis was performed from January 11, 2018, to November 9, 2018. All participants received NAC, breast operation, and axillary lymph node dissection. Participants underwent prospective arm measurements and symptom assessment after NAC completion and at 6-month intervals to 36 months postoperatively. Factors associated with lymphedema were defined as self-reported arm heaviness or swelling (lymphedema symptoms) or an arm volume increase of 10% or more (V10) or 20% or more (V20). A total of 486 patients (mean [SD] age, 50.1 [10.8] years) were included in this study. Median follow-up for the 3 measures was 2.2 to 3.0 years. Cumulative lymphedema incidence at 3 years was 37.8% (95% CI, 33.1%-43.2%) for lymphedema symptoms, 58.4% (95% CI, 53.2%-64.1%) for V10, and 36.9% (95% CI, 31.9%-42.6%) for V20. Increasing body mass index (hazard ratio [HR], 1.04; 95% CI, 1.01-1.06) and NAC for 144 days or longer (HR, 1.48; 95% CI, 1.01-2.17) were associated with lymphedema symptoms. The V20 incidence was higher among patients who received NAC for 144 days or longer (HR, 1.79; 95% CI, 1.19-2.68). The V10 incidence was highest in patients with 30 nodes or more removed (HR, 1.70; 95% CI, 1.15-2.52) and increased with number of positive nodes (HR, 1.03; 95% CI, 1.00-1.06). On multivariable analysis, obesity was significantly associated with lymphedema symptoms (HR, 1.03; 95% CI, 1.01-1.06), and NAC length was significantly associated with V20 (HR, 1.74; 95% CI, 1.15-2.62). In this study, longer NAC duration and obesity were associated with increased lymphedema incidence, suggesting that patients in these groups may benefit from enhanced prospective lymphedema surveillance.