Acupuncture for Breast Cancer Related Lymphedema: A Pilot Study

Awardee Recipient

  • Dhruv Singhal, MD

    Dhruv Singhal, MD

    Director of Lymphatic Surgery and Assistant Professor

    Beth Israel Deaconess Medical Center and Harvard Medical School

    Dhruv Singhal, MD serves as the Director of Lymphatic Surgery at the Beth Israel Deaconess Medical Center (Boston, MA) and Assistant Professor of Surgery at Harvard Medical School.  Dr. Singhal was previously the Director of Microsurgery at the...


  • 2017 - Pilot Grant

Research Summary

Lymphedema affects 140 million people worldwide and 3 million patients suffer from this disease in the United States alone. An important sub-population is patients with breast cancer related lymphedema (BCRL), which affects over 400,000 patients in the United States. Symptoms include fatigue, tightness, pain, and the potential of life threatening infections. Lymphedema is associated with a diminished quality of life (QOL) and BCRL patients incur twice the cost in medical expenses as breast cancer survivors who do not develop lymphedema.1 Physical therapy, the gold standard treatment, offers marginal relief. At Beth Israel Deaconess Medical Center (BIDMC), we offer surgical therapies for lymphedema including lymph node transfer and lymphovenous bypass. While these interventions alleviate symptoms and improve QOL, they do not provide a definitive cure and a large proportion of patients are not surgical candidates. Morbidity from lymphedema remains significant and there is an unmet need to rigorously explore alternative therapies.

While early data has demonstrated the benefits of acupuncture for BCRL2-8, the mechanism of action is poorly understood. Lymphedema is a progressive disorder that is initiated by inflammation and progresses to fibrosis. Moreover, as inflammation progresses in one region of the body, a systemic alteration in lymphatic function has been observed but is also poorly understood. Current avenues of basic science research are geared towards localizing molecular targets for inflammation9,10 and/or fibrosis11-13 in order to potentially prevent and/or treat lymphedema.

The goal of this proposal is to demonstrate the feasibility and preliminary efficacy of acupuncture for BCRL while beginning to explore the mechanistic underpinnings of this treatment. Specifically, we will conduct a single-arm proof-of-concept pilot study offering patients (N=20) with unilateral BCRL a 6-week acupuncture intervention with unprecedented rigorous monitoring of the affected upper extremity and the systemic response.

Specific Aims

(1)   Evaluate the feasibility [patient enrollment > 80%, completion of 9 acupuncture sessions, and ≥75% of patients completing all 3 testing visits] of executing a rigorous monitoring system of both the systemic and local response to lymphedema following acupuncture therapy.

(2)   Determine preliminary efficacy of treatment from local (circumferential measurements, bioimpedance spectroscopy, perometry, and durometry), systemic (IL4, IL10, TNFb), and patient centered perspectives (LYMQOL, a quality of life measure for limb lymphedema14).

We hypothesize that the beneficial effect of acupuncture in BCRL patients is achieved through a reduction in the extracellular fluid in the affected extremity. We further conjecture that this change in fluid volume is related to changes in the systemic inflammatory response, and that this will also result in improvements in symptoms and quality of life.

Our innovation arises from the unprecedented battery of testing available at the BIDMC Lymphedema Clinic which will allow us to better elucidate the potential mechanism of action acupuncture has on lymphedema. Specifically, our institution supports 2 certified lymphedema therapists who have been provided with the state of the art lymphedema monitoring equipment. We maintain a rigorous methodology of long board extremity measurements allowing for measurements every 4cm and algorithmic volume calculation with the truncated cone formula. We utilize bioimpedance spectroscopy as a routine method of assessing changes in extracellular fluid. We monitor changes in extremity volume utilizing perometry. Finally, an IRB approved experimental durometer is utilized to assess subtle skin changes in lymphedema patients. All of our patients are also monitored for patient centered outcomes utilizing the LYMQOL. The above objective measures are monitored prospectively in our IRB approved REDcap15 BIDMC Lymphedema Repository. Finally, our institution has a core laboratory dedicated to evaluation of inflammatory markers which will allow us to begin exploring the mechanistic underpinnings of the affect of acupuncture on lymphedema.


  1.  Shih, Y.-C. T. et al. Incidence, Treatment Costs, and Complications of Lymphedema After Breast
    Cancer Among Women of Working Age: A 2-Year Follow-Up Study. Journal of Clinical Oncology 27,
    2007–2014 (2009).
  2. Alem, M. & Gurgel, M. S. C. Acupuncture in the rehabilitation of women after breast cancer surgery–a case series. Acupunct Med 26, 87–93 (2008).
  3. de Valois, B. A., Young, T. E. & Melsome, E. Assessing the feasibility of using acupuncture and
    moxibustion to improve quality of life for cancer survivors with upper body lymphoedema. European
    Journal of Oncology Nursing 16, 301–309 (2012).
  4. Cassileth, B. R. et al. A safety and efficacy pilot study of acupuncture for the treatment of chronic
    lymphoedema. Acupunct Med 29, 170–172 (2011).
  5. Cassileth, B. R. et al. Acupuncture in the treatment of upper-limb lymphedema. Cancer 119, 2455–2461
  6. Smith, C. A., Pirotta, M. & Kilbreath, S. A feasibility study to examine the role of acupuncture to reduce symptoms of lymphoedema after breast cancer: a randomised controlled trial. Acupunct Med 32, 387–393 (2014).
  7. Jeong, Y. J. et al. Treatment of Lymphedema with SaamAcupuncture in Patients with Breast Cancer: A Pilot Study. Medical Acupuncture 27, 206–215 (2015).
  8. Yao, C. et al. Effects of warm acupuncture on breast cancer–related chronic lymphedema: a randomized controlled trial. Curr. Oncol. 23, 27–8 (2016).
  9. Rockson, S. G. The Lymphatics and the Inflammatory Response: Lessons Learned from Human
    Lymphedema. Lymphatic Research and Biology 11, 117–120 (2013).
  10. Lin, S. et al. Prospective Transcriptomic Pathway Analysis of Human Lymphatic Vascular Insufficiency: Identification and Validation of a Circulating Biomarker Panel. PLoS ONE 7, e52021–11 (2012).
  11. Zampell, J. C. et al. CD4+ Cells Regulate Fibrosis and Lymphangiogenesis in Response to Lymphatic Fluid Stasis. PLoS ONE 7, e49940 (2012).
  12. Ghanta, S. et al. Regulation of inflammation and fibrosis by macrophages in lymphedema. Am J Physiol Heart Circ Physiol 308, H1065–H1077 (2015).
  13. Hespe, G. E., Nores, G. G., Huang, J.-J. & Mehrara, B. J. Pathophysiology of lymphedema-Is there a chance for medication treatment? J. Surg. Oncol. (2016). doi:10.1002/jso.24414
  14. Keeley, V. et al. A quality of life measure for limb lymphedema. Journal of Lymphedema 5, 26–37
  15. Harris, P. A. et al. Research electronic data capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics support. Journal of Biomedical
    Informatics 42, 377–381 (2009).
  16. Suami, H. & Chang, D. W. Overview of Surgical Treatments for Breast Cancer–Related Lymphedema.Plastic and reconstructive surgery 126, 1853–1863 (2010).
  17. Hahamoff, M. et al. Lymphedema Surveillance for Breast Cancer Patients Reveal the Promise of
    Surgical Prevention. Journal of Surgical Research 1–25 (2017).
  18. Ward, L. C. et al. Multi-frequency bioelectrical impedance augments the diagnosis and management of lymphoedema in post-mastectomy patients. Eur. J. Clin. Invest. 22, 751–754 (1992).
  19. Cornish, B. H. et al. Early diagnosis of lymphedema using multiple frequency bioimpedance.
    Lymphology 34, 2–11 (2001).
  20. Adams, R. H. & Alitalo, K. Molecular regulation of angiogenesis and lymphangiogenesis. Nat Rev Mol Cell Biol 8, 464–478 (2007).
  21. Liao, S. et al. Impaired lymphatic contraction associated with immunosuppression. Proceedings of the National Academy of Sciences 108, 18784–18789 (2011).
  22. Du, F. & Liu, S. Electroacupuncture with high frequency at acupoint ST-36 induces regeneration of lost enteric neurons in diabetic rats via GDNF and PI3K/AKT signal pathway. Am J Physiol Regul Integr Comp Physiol 309, R109–R118 (2015).
  23. Oke, S. L. & Tracey, K. J. The Inflammatory Reflex and the Role of Complementary and Alternative
    Medical Therapies. Annals of the New York Academy of Sciences 1172, 172–180 (2009).
  24. Song, C., Halbreich, U., Han, C., Leonard, B. E. & Luo, H. Imbalance between Pro- and Antiinflammatory Cytokines, and between Th1 and Th2 Cytokines in Depressed Patients: The Effect of Electroacupuncture or Fluoxetine Treatment. Pharmacopsychiatry 42, 182–188 (2009).
  25. McDonald, J. L., Cripps, A. W. & Smith, P. K. Review Article Mediators, Receptors, and Signalling Pathways in the Anti-Inflammatory and Antihyperalgesic Effects of Acupuncture. Evidence-Based
    Complementary and Alternative Medicine 1–10 (2015). doi:10.1155/2015/975632
  26. Brorson, H., Svensson, B. & Ohlin, K. in Lymphedema: Presentation, Diagnosis, and Treatment (eds.
    Greene, A. K., Slavin, S. A. & Brorson, H.) 115–123 (2015).
  27. Czerniec, S. A. et al. Assessment of Breast Cancer-Related Arm Lymphedema—Comparison of
    Physical Measurement Methods and Self-Report. Cancer Investigation 28, 54–62 (2009).
  28. Tierney, S., Aslam, M., Rennie, K. & Grace, P. Infrared optoelectronic volumetry, the ideal way to
    measure limb volume. Eur J Vasc Endovasc Surg 12, 412–417 (1996).
  29. Stanton, A. W., Northfield, J. W., Holroyd, B., Mortimer, P. S. & Levick, J. R. Validation of an
    optoelectronic limb volumeter (Perometer). Lymphology 30, 77–97 (1997).
  30. Stanton, A. W., Badger, C. & Sitzia, J. Non-invasive assessment of the lymphedematous limb.
    Lymphology 33, 122–135 (2000).
  31. Chen, H. C., O’Brien, B. M., Pribaz, J. J. & Roberts, A. H. The use of tonometry in the assessment of
    upper extremity lymphoedema. Br J Plast Surg 41, 399–402 (1988).
  32. Clodius, L., Deak, L. & Piller, N. B. A new instrument for the evaluation fo tissue tonicity in
    lymphoedema. Lymphology 9, 1–5 (1976).
  33. Filshie, J. Safety aspects of acupuncture in palliative care. Acupunct Med 19, 117–122 (2001).