Neoadjuvant Chemotherapy Duration and Obesity May Be Associated With Increased Risk of Lymphedema in Some Women With Breast Cancer


Key Points

  • According to different definitions of lymphedema, risk factors included increasing BMI, increasing duration of neoadjuvant chemotherapy, and increasing number of nodes removed.
  • On multivariate analysis, increased BMI and longer duration of neoadjuvant chemotherapy were associated with increased lymphedema risk.   

In a cohort study reported in JAMA Surgery, Armer et al found that longer duration of neoadjuvant chemotherapy and increasing body mass index (BMI) were associated with increased risk of lymphedema in women with node-positive breast cancer who received neoadjuvant chemotherapy and axillary dissection.

Study Details

The study included data from 486 evaluable women with cT0-T4N1-2M0 breast cancer and axillary nodal metastasis at diagnosis enrolled in the American College of Surgeons Oncology Group Z1071 (Alliance for Clinical Trials in Oncology) trial conducted between January 2009 and December 2012. All patients received neoadjuvant chemotherapy, breast surgery, and axillary lymph node dissection. Arm measurements and symptom assessments were conducted after neoadjuvant chemotherapy completion and at 6-month intervals for up to 36 months after surgery. Lymphedema was assessed as arm heaviness or swelling (self-reported lymphedema symptoms) or arm volume increase of ≥ 10% (V10) or ≥ 20% (V20). Patients had a mean age of 50 years.

Risk for Lymphedema

Median follow-up for the lymphedema measures was 2.2 to 3.0 years.

The cumulative incidence of lymphedema at 3 years was 37.8% according to self-reported lymphedema symptoms, 58.4% for V10, and 36.9% for V20. Factors associated with increased risk of lymphedema symptoms were increasing BMI (hazard ratio [HR] per unit increase = 1.04, 95% confidence interval [CI] = 1.01–1.06) and neoadjuvant chemotherapy for ≥ 144 days (HR = 1.48, 95% CI = 1.01–2.17). V20 incidence was higher among patients who had received neoadjuvant chemotherapy for ≥ 144 days (HR = 1.79, 95% CI = 1.19–2.68). V10 incidence was highest in patients with ≥ 30 nodes 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).  Risk according to symptoms was significantly greater among patients with BMI ≥ 30 kg/m2 vs < 30 kg/m2 (P = .01). On multivariate analysis, increasing BMI was significantly associated with lymphedema symptoms (HR = 1.03, 95% CI = 1.01–1.06) and neoadjuvant chemotherapy length ≥ 144 days was significantly associated with V20 (HR = 1.74, 95% CI = 1.15–2.62).

The investigators concluded: “In this study, longer neoadjuvant chemotherapy duration and obesity were associated with increased lymphedema incidence, suggesting that patients in these groups may benefit from enhanced prospective lymphedema surveillance.”

Jane M. Armer, PhD, RN, CLT, of the Ellis Fischel Cancer Center, Sinclair School of Nursing, University of Missouri, Columbia, and Judy C. Boughey, MD, of the Department of Surgery, Mayo Clinic, Rochester, are the corresponding authors for the JAMA Surgery article.

Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit


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