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

Jane M. Armer1 & Karla V. Ballman2 & Linda McCall3 & Nathan C. Armer1 & Yuanlu Sun1 & Tipparat Udmuangpia1 & Kelly K. Hunt4 & Elizabeth A. Mittendorf4 & David R. Byrd5 & Thomas B. Julian6 & Judy C. Boughey7. Supportive Care in Cancer 2018

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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

Jane M. Armer1 & Karla V. Ballman2 & Linda McCall3 & Nathan C. Armer1 & Yuanlu Sun1 & Tipparat Udmuangpia1 & Kelly K. Hunt4 & Elizabeth A. Mittendorf4 & David R. Byrd5 & Thomas B. Julian6 & Judy C. Boughey7.  Supportive Care in Cancer 2018.

Purpose 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.

Methods Z1071 enrolled patient with cT0-4, N1-2, M0 disease treated with neo adjuvant chemotherapy. All patients underwent axillary dissection. Bilateral limb volumes, circumferences, and related symptoms were assessed pre-surgery, 1–2 weeks postsurgery, 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.

Results 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).

Conclusions 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.

Main findings

  • Limb measurements were taken on both arms at five anatomic locations:(1) theaxilla,(2) halfway from the ante cubital fossa to the axilla, (3) antecubital fossa, (4) halfway from the antecubital fossa to the wrist, and (5) the wrist, with volume calculated using the truncated cone formula [14]. Symptoms were assessed by the Lymphedema Breast Cancer Questionnaire (LBCQ) .
  • Self-reported symptoms peaked in the immediate postoperative period, then declined over the subsequent 18months and remained relatively stable after 18months. The 36-month cumulative incidence of lymphedema based on symptoms of arm heaviness was 26.0% (95% CI 21.7, 31.1) and/or arm swelling was 30.9% (95% CI 26.3, 36.3). Lymphedema incidence rates were significantly lower when using the definition based on arm heaviness and/or swelling symptoms compared to either arm circumference ≥2 cm or arm volume ≥10% increase measurements.
  • The median time to lymphedema development by ≥10% limb volume increase was 1.7 years (95% CI 1.5-2.1) and by any ≥2 cm circumference increase was 1.1 years (95% CI 1.0-1.2). The median was not reached on symptom report of heaviness or swelling since less than half of the women reported these symptoms cumulatively over 3 years.
  • The over all findings of this study show that at 36 months post-surgery, lymphedema incidence was 60.3% (95% CI 55.0-66.2%) by the criterion of≥ 10% limb volume increase; and 75.4% (95% CI 70.8-80.2%) by ≥2 cm circumference increase criterion. Arm heaviness and arm swelling had a 3-year25-31% cumulative incidence, respectively. Lymphedema symptoms were relatively stable after 18 months.