Skip to main content

Advertisement

SpringerLink
Log in

Subclinical Lymphedema After Treatment for Breast Cancer: Risk of Progression and Considerations for Early Intervention

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Breast cancer-related lymphedema (BCRL) is a devastating complication of breast cancer (BC) treatment. The authors hypothesized that identifying subclinical lymphedema (SCL) presents an opportunity to prevent BCRL development. They aimed to assess rates of SCL progression (relative volume change [RVC], 5–10%) to BCRL (RVC, ≥10%) in women undergoing axillary surgery for BC via axillary lymph node dissection (ALND) or sentinel lymph node biopsy (SLNB).

Methods

Patients treated for BC were prospectively screened at preoperative baseline and throughout the follow-up period using the perometer. The cohort was stratified according to nodal surgery (ALND or SLNB) to analyze rates of progression to BCRL.

Results

The study cohort included 1790 patients. Of the 1359 patients who underwent SLNB, 331 (24.4%) experienced SCL, with 38 (11.5%) of these patients progressing to BCRL. Of the 431 patients who underwent ALND, 171 (39.7%) experienced SCL, with 67 (39.2%) of these patients progressing to BCRL. Relative to the patients without SCL, those more likely to experience BCRL were the ALND patients with early SCL (< 3 months postoperatively; hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.58–4.27; p = 0.0002) or late SCL (≥3 months postoperatively; HR, 3.14; 95% CI, 1.95–5.05; p < 0.0001) and the SLNB patients with early SCL (HR, 6.75; 95% CI, 3.8–11.98; p < 0.0001 or late SCL (HR, 3.02; 95% CI, 1.65–5.50; p = 0.0003).

Conclusion

The study suggests that patients with SCL after axillary nodal surgery for BC are more likely to progress to BCRL than those who do not experience SCL. This presents a tremendous opportunity for early intervention to prevent BCRL and improve the quality of life for women treated for BC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. DiSipio T, Rye S, Newman B, Hayes S. Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis. Lancet Oncol. 2013;14:500–15.

    Article  Google Scholar 

  2. Hespe GE, Nores GG, Huang JJ, Mehrara BJ. Pathophysiology of lymphedema: is there a chance for medication treatment? J Surg Oncol. 2017;115:96–8. https://doi.org/10.1002/jso.24414.

    Article  PubMed  Google Scholar 

  3. Gillespie TC, Sayegh HE, Brunelle CL, Daniell KM, Taghian AG. Breast cancer-related lymphedema: risk factors, precautionary measures, and treatments. Gland Surg. 2018;7:379–403. https://doi.org/10.21037/gs.2017.11.04.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Fu MR, Rosedale M. Breast cancer survivors’ experiences of lymphedema-related symptoms. J Pain Symptom Manage. 2009;38:849–59. https://doi.org/10.1016/j.jpainsymman.2009.04.030.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Tsai RJ, Dennis LK, Lynch CF, Snetselaar LG, Zamba GKD, Scott-Conner C. The risk of developing arm lymphedema among breast cancer survivors: a meta-analysis of treatment factors. Ann Surg Oncol. 2009;16:1959–72. https://doi.org/10.1245/s10434-009-0452-2.

    Article  PubMed  Google Scholar 

  6. Rebegea LF, Firescu D, Dumitru M, Anghel R. The incidence and risk factors for occurrence of arm lymphedema after treatment of breast cancer. Chirurgia. 2015;110:33–7.

    CAS  PubMed  Google Scholar 

  7. Shih Y-CT, Xu Y, Cormier JN, et al. Incidence, treatment costs, and complications of lymphedema after breast cancer among women of working age: a 2-year follow-up study. J Clin Oncol. 2009;27:2007–14. https://doi.org/10.1200/JCO.2008.18.3517.

    Article  PubMed  Google Scholar 

  8. Stout NL, Binkley JM, Schmitz KH, et al. A prospective surveillance model for rehabilitation for women with breast cancer. Cancer. 2012;118(Suppl 8):2191–200. https://doi.org/10.1002/cncr.27476.

    Article  PubMed  Google Scholar 

  9. Kaufman DI, Shah C, Vicini FA, Rizzi M. Utilization of bioimpedance spectroscopy in the prevention of chronic breast cancer-related lymphedema. Breast Cancer Res Treat. 2017;166:809–15. https://doi.org/10.1007/s10549-017-4451-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ridner SH, Dietrich MS, Cowher MS, et al. A randomized trial evaluating bioimpedance spectroscopy versus tape measurement for the prevention of lymphedema following treatment for breast cancer: interim analysis. Ann Surg Oncol. 2019;26:3250–59. https://doi.org/10.1245/s10434-019-07344-5.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Akita S, Nakamura R, Yamamoto N, et al. Early detection of lymphatic disorder and treatment for lymphedema following breast cancer. Plast Reconstr Surg. 2016;138:192e–202e. https://doi.org/10.1097/PRS.0000000000002337.

    Article  CAS  PubMed  Google Scholar 

  12. Ochalek K, Gradalski T, Partsch H. Preventing early postoperative arm swelling and lymphedema manifestation by compression sleeves after axillary lymph node interventions in breast cancer patients: a randomized controlled trial. J Pain Symptom Manage. 2017;54:346–54. https://doi.org/10.1016/j.jpainsymman.2017.04.014.

    Article  PubMed  Google Scholar 

  13. Soran A, Ozmen T, McGuire KP, et al. The importance of detection of subclinical lymphedema for the prevention of breast cancer-related clinical lymphedema after axillary lymph node dissection: a prospective observational study. Lymphat Res Biol. 2014;12:289–94. https://doi.org/10.1089/lrb.2014.0035.

    Article  PubMed  Google Scholar 

  14. National Lymphedema Network Medical Advisory Committee. Position Statement of the National Lymphedema Network: Screening and Measurement for Early Detection of Breast Cancer-Related Lymphedema. 2011.

  15. McLaughlin SA, Staley AC, Vicini F, et al. 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. 2017;24:2818–26. https://doi.org/10.1245/s10434-017-5982-4.

    Article  PubMed  Google Scholar 

  16. Paskett ED, Khakpour N, Moore H, O’Connor T. National Comprehensive Cancer Network Guidelines Version 2.2020: Survivorship: Lymphedema. 2020.

  17. International Society of Lymphology. The diagnosis and treatment of peripheral lymphedema: 2016 consensus document of the International Society of Lymphology. Lymphology. 2016;49:170–84. https://doi.org/10.1063/1.4704591.

    Article  CAS  Google Scholar 

  18. Brunelle C, Skolny M, Ferguson C, Swaroop M, O’Toole J, Taghian AG. Establishing and sustaining a prospective screening program for breast cancer-related lymphedema at the Massachusetts General Hospital: Lessons Learned. J Pers Med. 2015;5:153–64.

  19. Stanton AW, Northfield JW, Holroyd B, Mortimer PS, Levick JR. Validation of an optoelectronic limb volumeter (Perometer). Lymphology. 1997;30:77–97.

    CAS  PubMed  Google Scholar 

  20. Lee M-J, Boland RA, Czerniec S, Kilbreath SL. Reliability and concurrent validity of the perometer for measuring hand volume in women with and without lymphedema. Lymphat Res Biol. 2011;9:13–8. https://doi.org/10.1089/lrb.2010.0021.

    Article  PubMed  Google Scholar 

  21. Fu MR, Axelrod D, Cleland CM, et al. Symptom report in detecting breast cancer-related lymphedema. Breast Cancer Targets Ther. 2015;7:345–52. https://doi.org/10.2147/BCTT.S87854.

    Article  Google Scholar 

  22. Armer JM. The problem of post-breast cancer lymphedema: impact and measurement issues. Cancer Invest. 2005;23:76–83.

    Article  Google Scholar 

  23. Specht MC, Miller CL, Russell TA, et al. Defining a threshold for intervention in breast cancer-related lymphedema: what level of arm volume increase predicts progression? Breast Cancer Res Treat. 2013:1–10.

  24. Stout Gergich NL, Pfalzer LA, McGarvey C, Springer B, Gerber LH, Soballe P. Preoperative assessment enables the early diagnosis and successful treatment of lymphedema. Cancer. 2008;112:2809–19. https://doi.org/10.1002/cncr.23494.

    Article  PubMed  Google Scholar 

  25. Kilgore LJ, Korentager SS, Hangge AN, et al. Reducing breast cancer-related lymphedema (BCRL) through prospective surveillance monitoring using bioimpedance spectroscopy (BIS) and patient-directed self-interventions. Ann Surg Oncol. 2018;25:2948–52. https://doi.org/10.1245/s10434-018-6601-8.

    Article  PubMed  Google Scholar 

  26. Brown JC, Cheville AL, Tchou JC, Harris SR, Schmitz KH. Prescription and adherence to lymphedema self-care modalities among women with breast cancer-related lymphedema. Support Care Cancer. 2014;22:135–43. https://doi.org/10.1007/s00520-013-1962-9.

    Article  PubMed  Google Scholar 

  27. Shah C, Arthur DW, Wazer D, Khan A, Ridner S, Vicini F. The impact of early detection and intervention of breast cancer-related lymphedema: a systematic review. Cancer Med. 2016;5:1154–62. https://doi.org/10.1002/cam4.691.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Sayegh HE, Asdourian MS, Swaroop MN, et al. Diagnostic methods, risk factors, prevention, and management of breast cancer-related lymphedema: past, present, and future directions. Curr Breast Cancer Rep. 2017;9:111–21.

    Article  CAS  Google Scholar 

  29. Tierney S, Aslam M, Rennie K, Grace P. Infrared optoelectronic volumetry, the ideal way to measure limb volume. Eur J Vasc Endovasc Surg. 1996;12:412–7. https://doi.org/10.1016/S1078-5884(96)80005-0.

    Article  CAS  PubMed  Google Scholar 

  30. Sun F, Skolny MN, Swaroop MN, et al. The need for preoperative baseline arm measurement to accurately quantify breast cancer-related lymphedema. Breast Cancer Res Treat. 2016;157:229–40. https://doi.org/10.1007/s10549-016-3821-0.

    Article  CAS  PubMed  Google Scholar 

  31. Ancukiewicz M, Russell TA, Otoole J, et al. Standardized method for quantification of developing lymphedema in patients treated for breast cancer. Int J Radiat Oncol Biol Phys. 2011;79:1436–43. https://doi.org/10.1016/j.ijrobp.2010.01.001.

    Article  PubMed  Google Scholar 

  32. O’Toole J, Jammallo LS, Miller CL, Skolny MN, Specht MC, Taghian AG. Screening for breast cancer-related lymphedema: the need for standardization. Oncologist. 2013;18:350–2. https://doi.org/10.1634/theoncologist.2012-0387.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Sun F, Hall A, Tighe MP, et al. Perometry versus simulated circumferential tape measurement for the detection of breast cancer-related lymphedema. Breast Cancer Res Treat. 2018;172:83–91. https://doi.org/10.1007/s10549-018-4902-z.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Ancukiewicz M, Miller CL, Skolny MN, et al. Comparison of relative versus absolute arm size change as criteria for quantifying breast cancer-related lymphedema: the flaws in current studies and need for universal methodology. Breast Cancer Res Treat. 2012;135:145–52. https://doi.org/10.1007/s10549-012-2111-8.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Armer JM, Stewart BR. A comparison of four diagnostic criteria for lymphedema in a post-breast cancer population. Lymphat Res Biol. 2005;3:208–17. https://doi.org/10.1089/lrb.2005.3.208.

    Article  PubMed  Google Scholar 

  36. Borman P, Yaman A, Yasrebi S, Özdemir O. The importance of awareness and education in patients with breast cancer-related lymphedema. J Cancer Educ. 2017;32:629–33. https://doi.org/10.1007/s13187-016-1026-1.

    Article  PubMed  Google Scholar 

  37. Sherman KAKL. The role of information sources and objective risk status on lymphedema risk-minimization behaviors in women recently diagnosed with breast cancer. Oncol Nurs Forum. 2011;38:E27-36. https://doi.org/10.1188/11.ONF.E27-E36.

    Article  PubMed  Google Scholar 

  38. Fu MR, Chen CM, Haber J, Guth AA, Axelrod D. The effect of providing information about lymphedema on the cognitive and symptom outcomes of breast cancer survivors. Ann Surg Oncol. 2010;17:1847–53. https://doi.org/10.1245/s10434-010-0941-3.

    Article  PubMed  Google Scholar 

  39. Warren LEG, Miller CL, Horick N, et al. The impact of radiation therapy on the risk of lymphedema after treatment for breast cancer: a prospective cohort study. Int J Radiat Oncol Biol Phys. 2014;88:565–71. https://doi.org/10.1016/j.ijrobp.2013.11.232.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Johansson K, Branje E. Arm lymphoedema in a cohort of breast cancer survivors 10 years after diagnosis. Acta Oncol Madr. 2010;49:166–73. https://doi.org/10.3109/02841860903483676.

    Article  Google Scholar 

  41. Johansson K, Ochalek K, Hayes S. Prevention of arm lymphedema through the use of compression sleeves following breast cancer: results from a targeted literature review. Phys Ther Rev. 2020. https://doi.org/10.1080/10833196.2020.1822140.

    Article  Google Scholar 

  42. Foldi E. The treatment of lymphedema. Cancer. 1988; (12 Suppl A):2833–4.

  43. NCCN. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Survivorship.

  44. ISL. The diagnosis and treatment of peripheral lymphedema, . consensus document of the International Society of Lymphology. Lymphology. 2016;2016(49):170–84. https://doi.org/10.1063/1.4704591.

    Article  CAS  Google Scholar 

  45. McDuff SGR, Mina AI, Brunelle CL, et al. Timing of lymphedema after treatment for breast cancer: when are patients most at risk? Int J Radiat Oncol Biol Phys. 2019;103:62–70. https://doi.org/10.1016/j.ijrobp.2018.08.036.

    Article  PubMed  Google Scholar 

  46. Brunelle CL, Roberts SA, Horick NK, et al. Integrating symptoms into the diagnostic criteria for breast cancer-related lymphedema: applying results from a prospective surveillance program. Phys Ther. 2020;100:2186–97.

    Article  Google Scholar 

  47. Yahathugoda C, Weiler MJ, Rao R, et al. Use of a novel portable three-dimensional imaging system to measure limb volume and circumference in patients with filarial lymphedema. Am J Trop Med Hyg. 2017;97:1836–42. https://doi.org/10.4269/ajtmh.17-0504.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgment

The project was supported by award no. R01CA139118 (A. G. Taghian) and award no. P50CA08393 (A. G. Taghian) from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. This program was supported by the Adele McKinnon Research Fund for Breast Cancer-Related Lymphedema, the Heinz Family Foundation, and the Olayan-Xefos Family Fund for Breast Cancer Research.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Loryn K. Bucci BS, Madison C. Bernstein BA, Tessa C. Gillespie BS, Sacha A. Roberts BS, George E. Naoum MD, MMSCI & Alphonse G. Taghian MD, PhD, FASTRO

  2. Department of Physical and Occupational Therapy, Massachusetts General Hospital, Boston, MA, USA

    Cheryl L. Brunelle MScPT

  3. Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA

    Amy M. Shui MA

Authors
  1. Loryn K. Bucci BS
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cheryl L. Brunelle MScPT
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Madison C. Bernstein BA
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Amy M. Shui MA
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tessa C. Gillespie BS
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sacha A. Roberts BS
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. George E. Naoum MD, MMSCI
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alphonse G. Taghian MD, PhD, FASTRO
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alphonse G. Taghian MD, PhD, FASTRO.

Ethics declarations

Disclosure

Alphonse G. Taghian has been loaned equipment from ImpediMed for use in an investigator-initiated clinical trial. Alphonse G. Taghian is on the Scientific Advisory Board of Puretech Health and is a previous consultant for VisionRT. Both involvements are unrelated to this study. Cheryl L. Brunelle is on the Scientific Advisory Board of Puretech Health. The remaining authors have no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bucci, L.K., Brunelle, C.L., Bernstein, M.C. et al. Subclinical Lymphedema After Treatment for Breast Cancer: Risk of Progression and Considerations for Early Intervention. Ann Surg Oncol 28, 8624–8633 (2021). https://doi.org/10.1245/s10434-021-10173-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-021-10173-0

Search

Navigation