Lymphedema symptoms and limb measurement changes in breast cancer survivors treated with neoadjuvant chemotherapy and axillary dissection: results of American College of Surgeons Oncology Group (ACOSOG) Z1071 (Alliance) substudy
Lymphedema is a potential complication of breast cancer treatment. This longitudinal substudy aimed to prospectively assess arm measurements and symptoms following neoadjuvant chemotherapy and axillary dissection in the ACOSOG/Alliance Z1071 trial to characterize the optimal approach to define lymphedema.
Z1071 enrolled patients with cT0-4, N1-2, M0 disease treated with neoadjuvant chemotherapy. All patients underwent axillary dissection. Bilateral limb volumes, circumferences, and related symptoms were assessed pre-surgery, 1–2 weeks post-surgery, and semiannually for 36 months. Lymphedema definitions included volume increase ≥ 10% or limb circumference increase ≥ 2 cm. Symptoms were assessed by the Lymphedema Breast Cancer Questionnaire.
In 488 evaluable patients, lymphedema incidence at 3 years by ≥ 10%-volume-increase was 60.3% (95% CI 55.0–66.2%) and by ≥ 2 cm-circumference increase was 75.4% (95% CI 70.8–80.2%). Symptoms of arm swelling and heaviness decreased from post-surgery for the first 18 months and then were relatively stable. The 3-year cumulative incidence of arm swelling and heaviness was 26.0% (95% CI 21.7–31.1%) and 30.9% (95% CI 26.3–36.3%), respectively. There was limited agreement between the two measurements (kappa 0.27) and between symptoms and measurements (kappa coefficients ranging from 0.05–0.09).
Lymphedema incidence by limb volume and circumference gradually increased over 36 months post-surgery, whereas lymphedema symptoms were much lower. These findings underscore the importance of prospective surveillance and evaluation of both limb measurements and symptom assessment. Lymphedema incidence rates varied by definition. We recommend that ≥ 10% volume change criterion be used for lymphedema evaluation for referral for specialist care.
KeywordsLymphedema Clinical trials Neoadjuvant chemotherapy Prospective surveillance Breast cancer survivorship
Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number UG1CA189823 (Alliance for Clinical Trials in Oncology NCORP Grant), U10CA180821, U10CA180882, U10CA180790, U10CA180858, U10CA180868, and U10CA180888
Compliance with ethical standards
This research was carried out in full compliance with ethical standards for research conducted with human subjects.
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Conflict of interest
The authors declare no conflicts of interest. The authors have no financial relationship with the organization that sponsored the research. The authors have full control of all primary data and agree to allow the journal to review the source data, if requested.
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