Top

Published in:

Open Access 01-06-2015 | Clinical trial

Impact of adjuvant taxane-based chemotherapy on development of breast cancer-related lymphedema: results from a large prospective cohort

Authors: Meyha N. Swaroop, Chantal M. Ferguson, Nora K. Horick, Melissa N. Skolny, Cynthia L. Miller, Lauren S. Jammallo, Cheryl L. Brunelle, Jean A. O’Toole, Steven J. Isakoff, Michelle C. Specht, Alphonse G. Taghian

Published in: Breast Cancer Research and Treatment | Issue 2/2015

Abstract

Taxane-based chemotherapy for the treatment of breast cancer is associated with fluid retention in the extremities; however, its association with development of breast cancer-related lymphedema is unclear. We sought to determine if adjuvant taxane-based chemotherapy increased risk of lymphedema or mild swelling of the upper extremity. 1121 patients with unilateral breast cancer were prospectively screened for lymphedema with perometer measurements. Lymphedema was defined as a relative volume change (RVC) of ≥10 % from preoperative baseline. Mild swelling was defined as RVC 5- <10 %. Clinicopathologic characteristics were obtained via medical record review. Kaplan–Meier and Cox proportional hazard analyses were performed to determine lymphedema rates and risk factors. 29 % (324/1121) of patients were treated with adjuvant taxane-based chemotherapy. The 2-year cumulative incidence of lymphedema in the overall cohort was 5.27 %. By multivariate analysis, axillary lymph node dissection (ALND) (p < 0.0001), higher body mass index (p = 0.0007), and older age at surgery (p = 0.04) were significantly associated with increased risk of lymphedema; however, taxane chemotherapy was not significant when compared to no chemotherapy and non-taxane chemotherapy (HR 1.14, p = 0.62; HR 1.56, p = 0.40, respectively). Chemotherapy with docetaxel was significantly associated with mild swelling on multivariate analysis in comparison to both no chemotherapy and non-taxane chemotherapy groups (HR 1.63, p = 0.0098; HR 2.15, p = 0.02, respectively). Patients who receive taxane-based chemotherapy are not at an increased risk of lymphedema compared to patients receiving no chemotherapy or non-taxane adjuvant chemotherapy. Those treated with docetaxel may experience mild swelling, but this does not translate into subsequent lymphedema.

Paskett ED, Naughton MJ, McCoy TP et al (2007) The epidemiology of arm and hand swelling in premenopausal breast cancer survivors. Cancer Epidemiol Biomarkers Prev 16:775–782CrossRefPubMed

Sakorafas GH, Peros G, Cataliotti L et al (2006) Lymphedema following axillary lymph node dissection for breast cancer. Surg Oncol 15:153–165CrossRefPubMed

Hayes SC, Janda M, Cornish B et al (2008) Lymphedema after breast cancer: incidence, risk factors, and effect on upper body function. J Clin Oncol 26:3536–3542CrossRefPubMed

Jager G, Doller W, Roth R (2006) Quality-of-life and body image impairments in patients with lymphedema. Lymphology 39:193–200PubMed

Ridner SH (2009) The psycho-social impact of lymphedema. Lymphat Res Biol 7:109–112CrossRefPubMedCentralPubMed

Jammallo LS, Miller CL, Horick NK et al (2014) Factors associated with fear of lymphedema after treatment for breast cancer. Oncol Nurs Forum 41:473–483CrossRefPubMed

DiSipio T, Rye S, Newman B et al (2013) Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis. Lancet Oncol 14:500–515CrossRefPubMed

Norman SA, Localio AR, Kallan MJ et al (2010) Risk factors for lymphedema after breast cancer treatment. Cancer Epidemiol Biomarkers Prev 19:2734–2746CrossRefPubMedCentralPubMed

Yang EJ, Park WB, Seo KS et al (2010) Longitudinal change of treatment-related upper limb dysfunction and its impact on late dysfunction in breast cancer survivors: a prospective cohort study. J Surg Oncol 101:84–91CrossRefPubMed

10.

Lucci A, McCall LM, Beitsch PD et al (2007) 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 25:3657–3663CrossRefPubMed

11.

Park JH, Lee WH, Chung HS (2008) Incidence and risk factors of breast cancer lymphoedema. J Clin Nurs 17:1450–1459CrossRefPubMed

12.

Tsai RJ, Dennis LK, Lynch CF et al (2009) The risk of developing arm lymphedema among breast cancer survivors: a meta-analysis of treatment factors. Ann Surg Oncol 16:1959–1972CrossRefPubMed

13.

Ahmed RL, Schmitz KH, Prizment AE et al (2011) Risk factors for lymphedema in breast cancer survivors, the Iowa Women’s Health Study. Breast Cancer Res Treat 130:981–991CrossRefPubMedCentralPubMed

14.

Crosby MA, Card A, Liu J et al (2012) Immediate breast reconstruction and lymphedema incidence. Plast Reconstr Surg 129:789e–795eCrossRefPubMed

15.

Swenson KK, Nissen MJ, Leach JW et al (2009) Case-control study to evaluate predictors of lymphedema after breast cancer surgery. Oncol Nurs Forum 36:185–193CrossRefPubMed

16.

Soran A, D’Angelo G, Begovic M et al (2006) Breast cancer-related lymphedema—what are the significant predictors and how they affect the severity of lymphedema? Breast J 12:536–543CrossRefPubMed

17.

Nesvold IL, Dahl AA, Lokkevik E et al (2008) Arm and shoulder morbidity in breast cancer patients after breast-conserving therapy versus mastectomy. Acta Oncol 47:835–842CrossRefPubMed

18.

Ozaslan C, Kuru B (2004) Lymphedema after treatment of breast cancer. Am J Surg 187:69–72CrossRefPubMed

19.

Warren LE, Miller CL, Horick N et al (2014) 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 88:565–571CrossRefPubMedCentralPubMed

20.

Jammallo LS, Miller CL, Singer M et al (2013) Impact of body mass index and weight fluctuation on lymphedema risk in patients treated for breast cancer. Breast Cancer Res Treat 142:59–67CrossRefPubMed

21.

Togawa K, Ma H, Sullivan-Halley J et al (2014) Risk factors for self-reported arm lymphedema among female breast cancer survivors: a prospective cohort study. Breast Cancer Res 16:414-014-0414-xCrossRef

22.

Zhu YQ, Xie YH, Liu FH et al (2014) Systemic analysis on risk factors for breast cancer related lymphedema. Asian Pac J Cancer Prev 15:6535–6541CrossRefPubMed

23.

Lee SH, Min YS, Park HY et al (2012) Health-related quality of life in breast cancer patients with lymphedema who survived more than one year after surgery. J Breast Cancer 15:449–453CrossRefPubMedCentralPubMed

24.

Haddad P, Farzin M, Amouzegar-Hashemi F et al (2010) A multicentre cross-sectional study of arm lymphedema four or more years after breast cancer treatment in Iranian patients. Breast Cancer 17:281–285CrossRefPubMed

25.

Shah C, Wilkinson JB, Baschnagel A et al (2012) Factors associated with the development of breast cancer-related lymphedema after whole-breast irradiation. Int J Radiat Oncol Biol Phys 83:1095–1100CrossRefPubMed

26.

Shih YC, Xu Y, Cormier JN et al (2009) Incidence, treatment costs, and complications of lymphedema after breast cancer among women of working age: a 2-year follow-up study. J Clin Oncol 27:2007–2014CrossRefPubMed

27.

Kim M, Kim SW, Lee SU et al (2013) A model to estimate the risk of breast cancer-related lymphedema: combinations of treatment-related factors of the number of dissected axillary nodes, adjuvant chemotherapy, and radiation therapy. Int J Radiat Oncol Biol Phys 86:498–503CrossRefPubMed

28.

Gartner R, Jensen MB, Kronborg L et al (2010) Self-reported arm-lymphedema and functional impairment after breast cancer treatment—a nationwide study of prevalence and associated factors. Breast 19:506–515CrossRefPubMed

29.

Monleon S, Murta-Nascimento C, Bascuas I et al (2014) Lymphedema predictor factors after breast cancer surgery: a survival analysis. Lymphat Res Biol. doi:10.1089/lrb.2013.0042

30.

Meeske KA, Sullivan-Halley J, Smith AW et al (2009) Risk factors for arm lymphedema following breast cancer diagnosis in Black women and White women. Breast Cancer Res Treat 113:383–391CrossRefPubMed

31.

Henderson IC, Berry DA, Demetri GD et al (2003) Improved outcomes from adding sequential Paclitaxel but not from escalating Doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol 21:976–983CrossRefPubMed

32.

Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Peto R, Davies C et al (2012) Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 379:432–444CrossRef

33.

Martin M, Pienkowski T, Mackey J et al (2005) Adjuvant docetaxel for node-positive breast cancer. N Engl J Med 352:2302–2313CrossRefPubMed

34.

Martin M, Segui MA, Anton A et al (2010) Adjuvant docetaxel for high-risk, node-negative breast cancer. N Engl J Med 363:2200–2210CrossRefPubMed

35.

Mamounas EP, Bryant J, Lembersky B et al (2005) Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol 23:3686–3696CrossRefPubMed

36.

Goble S, Bear HD (2003) Emerging role of taxanes in adjuvant and neoadjuvant therapy for breast cancer: the potential and the questions. Surg Clin N Am 83:943–971CrossRefPubMed

37.

Ohsumi S, Shimozuma K, Ohashi Y et al (2012) Subjective and objective assessment of edema during adjuvant chemotherapy for breast cancer using taxane-containing regimens in a randomized controlled trial: the national surgical adjuvant study of breast cancer 02. Oncology 82:131–138CrossRefPubMed

38.

Qin YY, Li H, Guo XJ et al (2011) Adjuvant chemotherapy, with or without taxanes, in early or operable breast cancer: a meta-analysis of 19 randomized trials with 30698 patients. PLoS ONE 6:e26946CrossRefPubMedCentralPubMed

39.

Bronstad A, Berg A, Reed RK (2004) Effects of the taxanes paclitaxel and docetaxel on edema formation and interstitial fluid pressure. Am J Physiol Heart Circ Physiol 287:H963–H968CrossRefPubMed

40.

Piccart MJ, Klijn J, Paridaens R et al (1997) Corticosteroids significantly delay the onset of docetaxel-induced fluid retention: final results of a randomized study of the European Organization for Research and Treatment of Cancer Investigational Drug Branch for Breast Cancer. J Clin Oncol 15:3149–3155PubMed

41.

Jung SY, Shin KH, Kim M et al (2014) Treatment factors affecting breast cancer-related lymphedema after systemic chemotherapy and radiotherapy in stage II/III breast cancer patients. Breast Cancer Res Treat 148:91–98CrossRefPubMed

42.

Kilbreath SL, Lee MJ, Refshauge KM et al (2013) Transient swelling versus lymphoedema in the first year following surgery for breast cancer. Support Care Cancer 21:2207–2215CrossRefPubMed

43.

Lee MJ, Beith J, Ward L et al (2014) Lymphedema following taxane-based chemotherapy in women with early breast cancer. Lymphat Res Biol 12:282–288CrossRefPubMed

44.

Stanton AW, Northfield JW, Holroyd B et al (1997) Validation of an optoelectronic limb volumeter (Perometer). Lymphology 30:77–97PubMed

45.

Tierney S, Aslam M, Rennie K et al (1996) Infrared optoelectronic volumetry, the ideal way to measure limb volume. Eur J Vasc Endovasc Surg 12:412–417CrossRefPubMed

46.

O’Toole J, Jammallo LS, Skolny MN et al (2013) Lymphedema following treatment for breast cancer: a new approach to an old problem. Crit Rev Oncol Hematol 88:437–446CrossRefPubMedCentralPubMed

47.

Ancukiewicz M, Russell TA, Otoole J et al (2011) Standardized method for quantification of developing lymphedema in patients treated for breast cancer. Int J Radiat Oncol Biol Phys 79:1436–1443CrossRefPubMedCentralPubMed

48.

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

49.

Specht MC, Miller CL, Russell TA et al (2013) Defining a threshold for intervention in breast cancer-related lymphedema: what level of arm volume increase predicts progression? Breast Cancer Res Treat 140:485–494CrossRefPubMedCentralPubMed

50.

Mackey JR, Martin M, Pienkowski T et al (2013) Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial. Lancet Oncol 14:72–80CrossRefPubMed

51.

Ferguson T, Wilcken N, Vagg R et al (2007) Taxanes for adjuvant treatment of early breast cancer. Cochrane Database Syst Rev 4:CD004421PubMed

52.

De Laurentiis M, Cancello G, D’Agostino D et al (2008) Taxane-based combinations as adjuvant chemotherapy of early breast cancer: a meta-analysis of randomized trials. J Clin Oncol 26:44–53CrossRefPubMed

53.

Sparano JA, Wang M, Martino S et al (2008) Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med 358:1663–1671CrossRefPubMedCentralPubMed

54.

Giordano SH, Lin YL, Kuo YF et al (2012) Decline in the use of anthracyclines for breast cancer. J Clin Oncol 30:2232–2239CrossRefPubMedCentralPubMed

55.

Semb KA, Aamdal S, Oian P (1998) Capillary protein leak syndrome appears to explain fluid retention in cancer patients who receive docetaxel treatment. J Clin Oncol 16:3426–3432PubMed

56.

Behar A, Pujade-Lauraine E, Maurel A et al (1997) The pathophysiological mechanism of fluid retention in advanced cancer patients treated with docetaxel, but not receiving corticosteroid comedication. Br J Clin Pharmacol 43:653–658CrossRefPubMedCentralPubMed

57.

Hugenholtz-Wamsteker W, Robbeson C, Nijs J et al (2014) The effect of docetaxel on developing oedema in patients with breast cancer: a systematic review. Eur J Cancer Care (Engl). doi:10.1111/ecc.12261

58.

Park SI, Jeon WH, Jeung HJ et al (2014) Clinical features of docetaxel chemotherapy-related lymphedema. Lymphat Res Biol 12:197–202CrossRefPubMed

59.

Vignes S, Lebrun-Vignes B (2007) Sclerodermiform aspect of arm lymphoedema after treatment with docetaxel for breast cancer. J Eur Acad Dermatol Venereol 21:1131–1133CrossRefPubMed

60.

Taylor R, Jayasinghe UW, Koelmeyer L et al (2006) Reliability and validity of arm volume measurements for assessment of lymphedema. Phys Ther 86:205–214PubMed

61.

Deltombe T, Jamart J, Recloux S et al (2007) Reliability and limits of agreement of circumferential, water displacement, and optoelectronic volumetry in the measurement of upper limb lymphedema. Lymphology 40:26–34PubMed

62.

Ancukiewicz M, Miller CL, Skolny MN et al (2012) 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 135:145–152CrossRefPubMedCentralPubMed

63.

Stout Gergich NL, Pfalzer LA, McGarvey C et al (2008) Preoperative assessment enables the early diagnosis and successful treatment of lymphedema. Cancer 112:2809–2819CrossRefPubMed

64.

65.

Specht MC, Miller CL, Skolny MN et al (2013) Residual lymph node disease after neoadjuvant chemotherapy predicts an increased risk of lymphedema in node-positive breast cancer patients. Ann Surg Oncol 20:2835–2841CrossRefPubMed

66.

Soran A, Ozmen T, McGuire KP et al (2014) 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 12:289–294CrossRefPubMed

67.

Ostby PL, Armer JM, Dale PS et al (2014) Surveillance recommendations in reducing risk of and optimally managing breast cancer-related lymphedema. J Pers Med 4:424–447CrossRefPubMedCentralPubMed

68.

Cormier JN, Xing Y, Zaniletti I et al (2009) Minimal limb volume change has a significant impact on breast cancer survivors. Lymphology 42:161–175PubMedCentralPubMed

Title: Impact of adjuvant taxane-based chemotherapy on development of breast cancer-related lymphedema: results from a large prospective cohort
Authors: Meyha N. Swaroop
Chantal M. Ferguson
Nora K. Horick
Melissa N. Skolny
Cynthia L. Miller
Lauren S. Jammallo
Cheryl L. Brunelle
Jean A. O’Toole
Steven J. Isakoff
Michelle C. Specht
Alphonse G. Taghian
Publication date: 01-06-2015
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 2/2015
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-015-3408-1

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2015

Relative dose intensity and therapy efficacy in different breast cancer molecular subtypes: a retrospective study of early stage breast cancer patients treated with neoadjuvant chemotherapy

Retraction Note to: Suppression of the xCT–CD44v antiporter system sensitizes triple-negative breast cancer cells to doxorubicin

Progesterone receptor A predominance is a discriminator of benefit from endocrine therapy in the ATAC trial

Adjuvant dose-dense chemotherapy in breast cancer: a systematic review and meta-analysis of randomized trials

RETRACTED ARTICLE: Enhancement of doxorubicin efficacy through suppression of serine synthesis in triple-negative breast cancer

Body mass index associated with genome-wide methylation in breast tissue

Keynote webinar | Spotlight on antibody–drug conjugates in cancer