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01-09-2013 | Breast Oncology

Residual Lymph Node Disease After Neoadjuvant Chemotherapy Predicts an Increased Risk of Lymphedema in Node-Positive Breast Cancer Patients

Authors: Michelle C. Specht, MD, Cynthia L. Miller, BS, Melissa N. Skolny, MSHA, Lauren S. Jammallo, BS, Jean O’Toole, PT, MPH, Nora Horick, MS, Steven J. Isakoff, MD, PhD, Barbara L. Smith, MD, PhD, Alphonse G. Taghian, MD, PhD

Published in: Annals of Surgical Oncology | Issue 9/2013

Abstract

Background

Axillary lymph node dissection (ALND) is recommended for patients with clinically node-positive breast cancer and carries a risk of lymphedema >30 %. Patients with node-positive breast cancer may consider neoadjuvant chemotherapy, which can reduce node positivity. We sought to determine if neoadjuvant chemotherapy reduced the risk of lymphedema in patients undergoing ALND for node-positive breast cancer.

Methods

The 229 patients who underwent unilateral ALND and chemotherapy were divided into two groups: 30 % (68/229) had neoadjuvant and 70 % (161/229) had adjuvant chemotherapy. Prospective arm volumes were measured via perometry preoperatively and at 3- to 7-month intervals after surgery. Lymphedema was defined as relative volume change (RVC) ≥10 %, >3 months from surgery. Kaplan–Meier curves and multivariate regression models were used to identify risk factors for lymphedema.

Results

Fifteen percent (10/68) of neoadjuvant patients compared with 23 % (37/161) of adjuvant patients developed RVC ≥10 % (hazard ratio = 0.76, p = 0.39). For all patients, body mass index was significantly associated with lymphedema (p = 0.0003). For neoadjuvant patients, residual lymph node disease after chemotherapy was associated with a ninefold greater risk of lymphedema compared to those without residual disease (p = 0.038).

Conclusions

Patients who underwent neoadjuvant chemotherapy did not have a statistically significant reduction in risk of lymphedema. Among patients who receive neoadjuvant chemotherapy, residual lymph node disease predicted a greater risk of lymphedema. These patients should be closely monitored for lymphedema and possible early intervention for the condition.

Nederend J, Duijm LE, Voogd AC, Groenewoud JH, Jansen FH, Louwman MW. Trends in incidence and detection of advanced breast cancer at biennial screening mammography in The Netherlands: a population-based study. Breast Cancer Res. 2012;14(1):R10.

National Cancer Institute. Surveillance epidemiology and end results, SEER Stat Fact Sheets: Breast. 2011. http://seer.cancer.gov/statfacts/html/breast.html. Accessed 2 April 2012.

Ashikaga T, Krag DN, Land SR, et al. Morbidity results from the NSABP B-32 trial comparing sentinel lymph node dissection versus axillary dissection. J Surg Oncol. 2010;102(2):111–8.PubMedCrossRef

Wernicke AG, Shamis M, Sidhu KK, et al. Complication rates in patients with negative axillary nodes 10 years after local breast radiotherapy after either sentinel lymph node dissection or axillary clearance. Am J Clin Oncol. 2013;36(1):12–9.

Lucci A, McCall LM, Beitsch PD, et al. Surgical complications associated with sentinel lymph node dissection (SLND) plus axillary lymph node dissection compared with SLND alone in the American College of Surgeons Oncology Group Trial Z0011. J Clin Oncol. 2007;25(24):3657–63.PubMedCrossRef

McLaughlin SA, Wright MJ, Morris KT, et al. Prevalence of lymphedema in women with breast cancer 5 years after sentinel lymph node biopsy or axillary dissection: objective measurements. J Clin Oncol. 2008;26(32):5213–9.

Fisher B, Brown A, Mamounas E, et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol. 1997;15(7):2483–93.PubMed

Ahmed RL, Schmitz KH, Prizment AE, Folsom AR. Risk factors for lymphedema in breast cancer survivors, the Iowa Women’s Health Study. Breast Cancer Res Treat. 2011;130(3):981–91.

van der Veen P, De Voogdt N, Lievens P, Duquet W, Lamote J, Sacre R. Lymphedema development following breast cancer surgery with full axillary resection. Lymphology. 2004;37(4):206–8.PubMed

10.

Kissin MW, Querci della Rovere G, Easton D. Risk of lymphoedema following the treatment of breast cancer. Br J Surg. 1986;73(7):580–4.PubMedCrossRef

11.

Suneson BL, Lindholm C, Hamrin E. Clinical incidence of lymphoedema in breast cancer patients in Jonkoping County, Sweden. Eur J Cancer Care (Engl). 1996;5(1):7–12.CrossRef

12.

Querci della Rovere G, Ahmad I, Singh P, Ashley S, Daniels IR, Mortimer P. An audit of the incidence of arm lymphoedema after prophylactic level I/II axillary dissection without division of the pectoralis minor muscle. Ann R Coll Surg Engl. 2003;85(3):158–61.

13.

Pillai P, Sharma S, Ahmed SZ, DK V. Study of incidence of lymphedema in Indian patients undergoing axillary dissection for breast cancer. Indian J Surg Oncol. 2010;1(3):263–9.PubMedCrossRef

14.

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(5):1436–43.PubMedCrossRef

15.

Armer JM, Stewart BR. A comparison of four diagnostic criteria for lymphedema in a post-breast cancer population. Lymphat Res Biol. 2005;3(4):208–17.PubMedCrossRef

16.

Tsai RJ, Dennis LK, Lynch CF, Snetselaar LG, Zamba GK, Scott-Conner C. The risk of developing arm lymphedema among breast cancer survivors: a meta-analysis of treatment factors. Ann Surg Oncol. 2009;16(7):1959–72.

17.

Armer JM, Stewart BR, Shook RP. 30-Month post-breast cancer treatment lymphoedema. J Lymphoedema. 2009;4(1):14–8.PubMed

18.

Dawes DJ, Meterissian S, Goldberg M, Mayo NE. Impact of lymphoedema on arm function and health-related quality of life in women following breast cancer surgery. J Rehabil Med. 2008;40(8):651–8.PubMedCrossRef

19.

Chachaj A, Małyszczak K, Pyszel K, et al. Physical and psychological impairments of women with upper limb lymphedema following breast cancer treatment. Psychooncology. 2009;19(3):299–305.

20.

Rockson SG. Lymphedema. Am J Med. 2001;110(4):288–95.PubMedCrossRef

21.

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

22.

Erickson VS, Pearson ML, Ganz PA, Adams J, Kahn KL. Arm edema in breast cancer patients. J Natl Cancer Inst. 2001;93(2):96–111.PubMedCrossRef

23.

Kocak Z, Overgaard J. Risk factors of arm lymphedema in breast cancer patients. Acta Oncol. 2000;39(3):389–92.PubMedCrossRef

24.

Morrell RM, Halyard MY, Schild SE, Ali MS, Gunderson LL, Pockaj BA. Breast cancer-related lymphedema. Mayo Clin Proc. 2005;80(11):1480–4.PubMedCrossRef

25.

Sparaco A, Fentiman IS. 9. Arm lymphoedema following breast cancer treatment. Int J Clin Pract. 2002;56(2):107–10.PubMed

26.

Petrek JA, Pressman PI, Smith RA. Lymphedema: current issues in research and management. CA Cancer J Clin. 2000;50(5):292–307.PubMedCrossRef

27.

Rockson SG. Precipitating factors in lymphedema: myths and realities. Cancer. 1998;83(12 Suppl American):2814–6.

28.

Clark B. SJ, Harlow W. Incidence and risk of arm oedema following treatment for breast cancer: a three-year follow-up study. Q J Med. 2005;98:343–8.CrossRef

29.

Kopanski Z, Wojewoda T, Wojewoda A, et al. Influence of some anthropometric parameters on the risk of development of distal complications after mastectomy carried out because of breast carcinoma. Am J Hum Biol. 2003;15(3):433–9.PubMedCrossRef

30.

Helyer LK, Varnic M, Le LW, Leong W, McCready D. Obesity is a risk factor for developing postoperative lymphedema in breast cancer patients. Breast J. 2010;16(1):48–54.PubMedCrossRef

31.

Mak SS, Yeo W, Lee YM, et al. Predictors of lymphedema in patients with breast cancer undergoing axillary lymph node dissection in Hong Kong. Nurs Res. 2008;57(6):416–25.PubMedCrossRef

32.

Ridner SH, Dietrich MS, Kidd N. Breast cancer treatment-related lymphedema self-care: education, practices, symptoms, and quality of life. Support Care Cancer. 2011;19(5):631–7.

33.

Mak SS, Yeo W, Lee YM, et al. Risk factors for the initiation and aggravation of lymphoedema after axillary lymph node dissection for breast cancer. Hong Kong Med J. 2009;15(3 Suppl 4):8–12.PubMed

34.

Ozcinar B, Guler SA, Kocaman N, Ozkan M, Gulluoglu BM, Ozmen V. Breast cancer related lymphedema in patients with different loco-regional treatments. Breast. 2012;21(3):361–5.

35.

Larson D, Weinstein M, Goldberg I, et al. Edema of the arm as a function of the extent of axillary surgery in patients with stage I–II carcinoma of the breast treated with primary radiotherapy. Int J Radiat Oncol Biol Phys. 1986;12(9):1575–82.PubMedCrossRef

36.

Herd-Smith A, Russo A, Muraca MG, Del Turco MR, Cardona G. Prognostic factors for lymphedema after primary treatment of breast carcinoma. Cancer. 2001;92(7):1783–7.PubMedCrossRef

37.

Goffman TE, Laronga C, Wilson L, Elkins D. Lymphedema of the arm and breast in irradiated breast cancer patients: risks in an era of dramatically changing axillary surgery. Breast J. 2004;10(5):405–11.PubMedCrossRef

38.

Norman SA, Localio AR, Kallan MJ, et al. Risk factors for lymphedema after breast cancer treatment. Cancer Epidemiol Biomarkers Prev. 2010;19(11):2734–46.PubMedCrossRef

39.

Purushotham AD, Bennett Britton TM, Klevesath MB, Chou P, Agbaje OF, Duffy SW. Lymph node status and breast cancer-related lymphedema. Ann Surg. 2007;246(1):42–5.PubMedCrossRef

40.

Roses DF, Brooks AD, Harris MN, Shapiro RL, Mitnick J. Complications of level I and II axillary dissection in the treatment of carcinoma of the breast. Ann Surg. 1999;230(2):194–201.PubMedCrossRef

41.

Edwards TL. Prevalence and aetiology of lymphoedema after breast cancer treatment in southern Tasmania. Aust N Z J Surg. 2000;70(6):412–8.PubMedCrossRef

42.

Bar Ad V, Cheville A, Solin LJ, Dutta P, Both S, Harris EE. Time course of mild arm lymphedema after breast conservation treatment for early-stage breast cancer. Int J Radiat Oncol Biol Phys. 2010;76(1):85–90.

43.

Albertini JJ, Lyman GH, Cox C, et al. Lymphatic mapping and sentinel node biopsy in the patient with breast cancer. JAMA. 1996;276(22):1818–22.PubMedCrossRef

44.

Veronesi U, Paganelli G, Galimberti V, et al. Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes. Lancet. 1997;349(9069):1864–7.PubMedCrossRef

45.

Giuliano AE, Jones RC, Brennan M, Statman R. Sentinel lymphadenectomy in breast cancer. J Clin Oncol. 1997;15(6):2345–50.PubMed

46.

Borgstein PJ, Pijpers R, Comans EF, van Diest PJ, Boom RP, Meijer S. Sentinel lymph node biopsy in breast cancer: guidelines and pitfalls of lymphoscintigraphy and gamma probe detection. J Am Coll Surg. 1998;186(3):275–83.PubMedCrossRef

47.

Mamounas EP, Brown A, Anderson S, et al. Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer: results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2005;23(12):2694–702.PubMedCrossRef

Title: Residual Lymph Node Disease After Neoadjuvant Chemotherapy Predicts an Increased Risk of Lymphedema in Node-Positive Breast Cancer Patients
Authors: Michelle C. Specht, MD
Cynthia L. Miller, BS
Melissa N. Skolny, MSHA
Lauren S. Jammallo, BS
Jean O’Toole, PT, MPH
Nora Horick, MS
Steven J. Isakoff, MD, PhD
Barbara L. Smith, MD, PhD
Alphonse G. Taghian, MD, PhD
Publication date: 01-09-2013
Publisher: Springer US
Published in: Annals of Surgical Oncology / Issue 9/2013
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-012-2828-y

At a glance: The STEP trials

Springer Medicine

Residual Lymph Node Disease After Neoadjuvant Chemotherapy Predicts an Increased Risk of Lymphedema in Node-Positive Breast Cancer Patients

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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