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

Importance: Most lymphedema studies include a heterogeneous population and focus on patients treated with adjuvant chemotherapy. Objective: To examine factors associated with lymphedema after neoadjuvant chemotherapy (NAC) and axillary lymph node dissection in women with node-positive breast cancer. Design, Setting, and Participants: 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. Interventions: 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. Main Outcomes and Measures: 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). Results: 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). Conclusions and Relevance: 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.