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.

Trial registration


This is a preview of subscription content, access via your institution.

Fig. 1


  1. 1.

    American Cancer Society (2018) Breast Cancer Facts & Figures 2017–2018. America Cancer Society. Accessed 30 June 2018

  2. 2.

    Armer JM, Radina ME, Porock D, Culbertson SD (2003) Predicting breast cancer-related lymphedema using self-reported symptoms. Nurs Res 52(6):370–379.

    Article  PubMed  Google Scholar 

  3. 3.

    Poage EG, Singer M, Armer JM, Poundall MD, Shellabarger MJ (2008) Demystifying lymphedema: development of the lymphedema putting evidence into practice card. Clin J Oncol Nurs 12(6):951–964.

    Article  PubMed  Google Scholar 

  4. 4.

    Dell DD, Doll C (2006) Caring for a patient with lymphedema. Nursing 36(6):49–51

    Article  Google Scholar 

  5. 5.

    Fu MR, Ridner SH, Armer J (2009) Post-breast cancer lymphedema: part 2. Am J Nurs 109(8):34–41; quiz 42.

    Article  PubMed  Google Scholar 

  6. 6.

    Nguyen TT, Hoskin TL, Habermann EB, Cheville AL, Boughey JC (2017) Breast Cancer-related lymphedema risk is related to multidisciplinary treatment and not surgery alone: results from a large cohort study. Ann Surg Oncol 24:2972–2980.

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    McLaughlin SA, DeSnyder SM, Klimberg S, Alatriste M, Boccardo F, Smith ML, Staley AC, Thiruchelvam PTR, Hutchison NA, Mendez J, MacNeill F, Vicini F, Rockson SG, Feldman SM (2017) Considerations for clinicians in the diagnosis, prevention, and treatment of breast cancer-related lymphedema, recommendations from an expert panel: part 2: preventive and therapeutic options. Ann Surg Oncol 24:2827–2835.

    Article  PubMed  Google Scholar 

  8. 8.

    McLaughlin SA, Staley AC, Vicini F, Thiruchelvam P, Hutchison NA, Mendez J, MacNeill F, Rockson SG, DeSnyder SM, Klimberg S, Alatriste M, Boccardo F, Smith ML, Feldman SM (2017) Considerations for clinicians in the diagnosis, prevention, and treatment of breast cancer-related lymphedema: recommendations from a multidisciplinary expert ASBrS panel : part 1: definitions, assessments, education, and future directions. Ann Surg Oncol 24:2818–2826.

    Article  PubMed  Google Scholar 

  9. 9.

    Norman SA, Localio AR, Potashnik SL, Simoes Torpey HA, Kallan MJ, Weber AL, Miller LT, DeMichele A, Solin LJ (2009) Lymphedema in breast cancer survivors: incidence, degree, time course, treatment, and symptoms. J Clin Oncol 27(3):390–397.

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Boccardo FM, Ansaldi F, Bellini C, Accogli S, Taddei G, Murdaca G, Campisi CC, Villa G, Icardi G, Durando P, Puppo F, Campisi C (2009) Prospective evaluation of a prevention protocol for lymphedema following surgery for breast cancer. Lymphology 42(1):1–9

    CAS  PubMed  Google Scholar 

  11. 11.

    Lawenda BD, Mondry TE, Johnstone PAS (2009) Lymphedema: a primer on the identification and management of a chronic condition in oncologic treatment. CA Cancer J Clin 59(1):8–24.

    Article  PubMed  Google Scholar 

  12. 12.

    Hayes SC, Johansson K, Stout NL, Prosnitz R, Armer JM, Gabram S, Schmitz KH (2012) Upper-body morbidity after breast cancer: incidence and evidence for evaluation, prevention, and management within a prospective surveillance model of care. Cancer 118(8 Suppl):2237–2249.

    Article  PubMed  Google Scholar 

  13. 13.

    Armer JM, Stewart BR, Smith K, Cormier JN (2011) Lymphedema following cancer treatment. In: Lester JL, Schmitt PA (eds) Cancer rehabilitation and survivorship: transdisciplinary approaches to personalized care. Oncology Nursing Society, Pittsburgh

    Google Scholar 

  14. 14.

    Armer JM, Stewart BR (2005) A comparison of four diagnostic criteria for lymphedema in a post-breast cancer population. Lymphat Res Biol 3(4):208–217.

    Article  PubMed  Google Scholar 

  15. 15.

    Czerniec SA, Ward LC, Refshauge KM, Beith J, Lee MJ, York S, Kilbreath SL (2010) Assessment of breast cancer-related arm lymphedema—comparison of physical measurement methods and self-report. Cancer Investig 28(1):54–62.

    CAS  Article  Google Scholar 

  16. 16.

    Bulley C, Gaal S, Coutts F, Blyth C, Jack W, Chetty U, Barber M, Tan CW (2013) Comparison of breast cancer-related lymphedema (upper limb swelling) prevalence estimated using objective and subjective criteria and relationship with quality of life. Biomed Res Int 2013:807569–807568.

    Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Ostby PL, Armer JM, Dale PS, Van Loo MJ, Wilbanks CL, Stewart BR (2014) Surveillance recommendations in reducing risk of and optimally managing breast cancer-related lymphedema. J Pers Med 4(3):424–447.

    Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Boughey JC, Suman VJ, Mittendorf EA, Ahrendt GM, Wilke LG, Taback B, Leitch AM, Kuerer HM, Bowling M, Flippo-Morton TS, Byrd DR, Ollila DW, Julian TB, McLaughlin SA, McCall L, Symmans WF, Le-Petross HT, Haffty BG, Buchholz TA, Nelson H, Hunt KK (2013) Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA 310(14):1455–1461.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Armer JM (2005) The problem of post-breast cancer lymphedema: impact and measurement issues. Cancer Investig 23(1):76–83.

    Article  Google Scholar 

  20. 20.

    Medical Advisory Committee NLN (2013) Position paper: screening and measurement for early detection of breast cancer related lymphedema. Position statement of the National Lymphedema Network. National Lymphedema Network, San Francisco

    Google Scholar 

  21. 21.

    National Accreditation Program for Breast Centers (2014) NAPBC standards manual 2014 edition. American College of Surgeons, Chicago

    Google Scholar 

  22. 22.

    Armer JM, Shook RP, Schneider MK, Brooks CW, Peterson J, Stewart BR (2009) Enhancing supportive-educative nursing systems to reduce risk of post-breast cancer lymphedema. Self Care Depend Care Nurs 17(1):6–15

    PubMed  PubMed Central  Google Scholar 

  23. 23.

    Stout NL, Pfalzer LA, Springer B, Levy E, McGarvey CL, Danoff JV, Gerber LH, Soballe PW (2012) Breast cancer-related lymphedema: comparing direct costs of a prospective surveillance model and a traditional model of care. Phys Ther 92(1):152–163.

    Article  PubMed  Google Scholar 

  24. 24.

    Cormier JN, Xing Y, Zaniletti I, Askew RL, Stewart BR, Armer JM (2009) Minimal limb volume change has a significant impact on breast cancer survivors. Lymphology 42(4):161–175

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Chance-Hetzler J, Armer J, Van Loo M, Anderson B, Harris R, Ewing R, Stewart B (2015) Prospective lymphedema surveillance in a clinic setting. J Pers Med 5(3):311–325.

    Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Singh C, De Vera M, Campbell KL (2013) The effect of prospective monitoring and early physiotherapy intervention on arm morbidity following surgery for breast cancer: a pilot study. Physiother Can 65(2):183–191.

    Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Binkley JM, Harris SR, Levangie PK, Pearl M, Guglielmino J, Kraus V, Rowden D (2012) Patient perspectives on breast cancer treatment side effects and the prospective surveillance model for physical rehabilitation for women with breast cancer. Cancer 118(8 Suppl):2207–2216.

    Article  PubMed  Google Scholar 

  28. 28.

    Petrek JA, Senie RT, Peters M, Rosen PP (2001) Lymphedema in a cohort of breast carcinoma survivors 20 years after diagnosis. Cancer 92(6):1368–1377

Download references


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

Author information



Corresponding authors

Correspondence to Jane M. Armer or Judy C. Boughey.

Ethics declarations

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.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Armer, J.M., Ballman, K.V., McCall, L. et al. 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. Support Care Cancer 27, 495–503 (2019).

Download citation


  • Lymphedema
  • Clinical trials
  • Neoadjuvant chemotherapy
  • Prospective surveillance
  • Breast cancer survivorship