The impact of lymphedema on health-related quality of life up to 10 years after breast cancer treatment

Mads G Jørgensen, Navid M Toyserkani, Frederik G Hansen, Anette Bygum, Jens A Sørensen, Mads G Jørgensen, Navid M Toyserkani, Frederik G Hansen, Anette Bygum, Jens A Sørensen

Abstract

The impact of breast cancer-related lymphedema (BCRL) on long-term quality of life is unknown. The aim of this study was to investigate the impact of BCRL on health-related quality of life (HRQoL) up to 10 years after breast cancer treatment. This regional population-based study enrolled patients treated for breast cancer with axillary lymph node dissection between January 1st 2007 and December 31th 2017. Follow up and assessments of the included patients were conducted between January 2019 and May 2020. The study outcome was HRQoL, evaluated with the Lymphedema Functioning, Disability and Health Questionnaire, the Disabilities of the Arm, Shoulder and Hand Questionnaire and the Short Form (36) Health Survey Questionnaire. Multivariate linear logistic regression models adjusted for confounders provided mean score differences (MDs) with 95% confidence intervals in each HRQoL scale and item. This study enrolled 244 patients with BCRL and 823 patients without BCRL. Patients with BCRL had significantly poorer HRQoL than patients without BCRL in 16 out of 18 HRQoL subscales, for example, in physical function (MDs 27, 95%CI: 24; 30), mental health (MDs 24, 95%CI: 21; 27) and social role functioning (MDs 20, 95%CI: 17; 23). Age, BMI, BCRL severity, hand and dominant arm affection had only minor impact on HRQoL (MDs < 5), suggesting a high degree of inter-individual variation in coping with lymphedema. This study showed that BCRL is associated with long-term impairments in HRQoL, especially affecting the physical and psychosocial domains. Surprisingly, BCRL diagnosis rather than clinical severity drove the largest impairments in HRQoL.

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1. Flowchart of the included patients.
Fig. 1. Flowchart of the included patients.
This figure shows the flowchart of patients treated for breast cancer in the region of southern Denmark. 1 = Exclusion and allocation based on procedure-, treatment- and diagnostic codes. 2 = outside or unknown Danish Breast Cancer Group treatment protocol. 3 = Exclusion of patients based on chart reviews and questionnaire responses. BC breast cancer.
Fig. 2. Patient reported symptoms of lymphedema.
Fig. 2. Patient reported symptoms of lymphedema.
These violin plots show lymphedema symptoms reported by breast cancer patients treated with axillary lymph node dissection with and without lymphedema. Symptoms reported on a 0–100 numeric rating scale where 0 denotes no symptoms and 100 denote worst symptoms and compared using student’s t-test. Violin plot thickness denotes the probability density of each reported symptom. The height of the violin plots denotes the range of responses. Thin dashed line denotes the median and thick dashed lines denote the interquartile range. A Arm heaviness symptom. B Arm stiffness symptom. C Arm swelling symptom. D Arm weakness. E Arm tingling. F Arm pain. G Arm tightness. **p-value < 0.001.

References

    1. Ferlay, J. et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase. No. 11 [Internet]. (International Agency for Research on Cancer, Lyon, France, 2013).
    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;14:500–515. doi: 10.1016/S1470-2045(13)70076-7.
    1. Armer JM, 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. 2019;27:495–503. doi: 10.1007/s00520-018-4334-7.
    1. Ridner SH, et al. L-Dex, arm volume, and symptom trajectories 24 months after breast cancer surgery. Cancer Med. 2020;9:5164–5173. doi: 10.1002/cam4.3188.
    1. Armer JM, et al. Factors associated with lymphedema in women with node-positive breast cancer treated with neoadjuvant chemotherapy and axillary dissection. JAMA Surg. 2019;154:800–809. doi: 10.1001/jamasurg.2019.1742.
    1. Teo I, Novy DM, Chang DW, Cox MG, Fingeret MC. Examining pain, body image, and depressive symptoms in patients with lymphedema secondary to breast cancer. Psychooncology. 2015;24:1377–1383. doi: 10.1002/pon.3745.
    1. Rogan S, et al. Therapy modalities to reduce lymphoedema in female breast cancer patients: a systematic review and meta-analysis. Breast Cancer Res. Treat. 2016;159:1–14. doi: 10.1007/s10549-016-3919-4.
    1. Jørgensen MG, Toyserkani NM, Sørensen JA. The effect of prophylactic lymphovenous anastomosis and shunts for preventing cancer-related lymphedema: a systematic review and meta-analysis. Microsurgery. 2017;38:576–585. doi: 10.1002/micr.30180.
    1. Scaglioni MF, Fontein DBY, Arvanitakis M, Giovanoli P. Systematic review of lymphovenous anastomosis (LVA) for the treatment of lymphedema. Microsurgery. 2017;37:947–953. doi: 10.1002/micr.30246.
    1. Dionigi F, et al. The institution of a Multi-disciplinary Italian Breast Unit: Reflections of the first psychosocial research study results on distress and quality of life. Breast J. 2019;25:678–681. doi: 10.1111/tbj.13244.
    1. Boehmke MM, Dickerson SS. The diagnosis of breast cancer: transition from health to illness. Oncol. Nurs. Forum. 2006;33:1121–1127. doi: 10.1188/06.ONF.1121-1127.
    1. Jørgensen, M. G., Toyserkani, N. M., Hansen, F. C. G., Thomsen, J. B. & Sørensen, J. A. Prospective validation of indocyanine green lymphangiography staging of breast cancer-related lymphedema. Cancers (Basel). 13, 1540 (2021).
    1. Lee TS, Morris CM, Czerniec SA, Mangion AJ. Does lymphedema severity affect quality of life? simple question. challenging answers. Lymphat. Res. Biol. 2018;16:85–91. doi: 10.1089/lrb.2016.0049.
    1. Kim G, et al. MRI staging of upper extremity secondary lymphedema: correlation with clinical measurements. Eur. Radiol. 2020;30:4686–4694. doi: 10.1007/s00330-020-06790-0.
    1. Wiser I, et al. Preoperative assessment of upper extremity secondary lymphedema. Cancers (Basel). 2020;12:135. doi: 10.3390/cancers12010135.
    1. Devoogdt N, Van Kampen M, Geraerts I, Coremans T, Christiaens M-R. Lymphoedema Functioning, Disability and Health Questionnaire (Lymph-ICF): reliability and validity. Phys. Ther. 2011;91:944–957. doi: 10.2522/ptj.20100087.
    1. De Vrieze T, et al. Responsiveness of the lymphedema functioning, disability, and health questionnaire for upper limb lymphedema in patients with breast cancer-related lymphedema. Lymphat. Res. Biol. 2020;18:365–373. doi: 10.1089/lrb.2019.0073.
    1. De Vrieze, T. et al. Cross-cultural validation of the French version of the Lymphedema Functioning, Disability and Health Questionnaire for Upper Limb Lymphedema (Lymph-ICF-UL). Disabil. Rehabil. 10.1080/09638288.2020.1716271 (2020).
    1. Toyserkani NM, Jørgensen MG, Haugaard K, Sørensen JA. Seroma indicates increased risk of lymphedema following breast cancer treatment: a retrospective cohort study. Breast. 2017;32:102–104. doi: 10.1016/j.breast.2017.01.009.
    1. Christiansen P, Ejlertsen B, Jensen MB, Mouridsen H. Danish breast cancer cooperative group. Clin. Epidemiol. 2016;8:445–449. doi: 10.2147/CLEP.S99457.
    1. Lynge E, Sandegaard JL, Rebolj M. The Danish National Patient Register. Scand. J. Public Health. 2011;39:30–33. doi: 10.1177/1403494811401482.
    1. Thygesen LC, Daasnes C, Thaulow I, Brønnum-Hansen H. Introduction to Danish (nationwide) registers on health and social issues: Structure, access, legislation, and archiving. Scand. J. Public Health. 2011;39:12–16. doi: 10.1177/1403494811399956.
    1. Gärtner R, et al. Self-reported arm-lymphedema and functional impairment after breast cancer treatment-A nationwide study of prevalence and associated factors. Breast. 2010;19:506–515. doi: 10.1016/j.breast.2010.05.015.
    1. Vassard D, et al. Psychological consequences of lymphoedema associated with breast cancer: a prospective cohort study. Eur. J. Cancer. 2010;46:3211–3218. doi: 10.1016/j.ejca.2010.07.041.
    1. De Vrieze, T. et al. Physical activity level and age contribute to functioning problems in patients with breast cancer-related lymphedema: a multicentre cross-sectional study. Support Care Cancer28, 5717–5731 10.1007/s00520-020-05375-3 (2020).
    1. Rosian K, Stanak M. Efficacy and safety assessment of lymphovenous anastomosis in patients with primary and secondary lymphoedema: a systematic review of prospective evidence. Microsurgery. 2019;39:763–772. doi: 10.1002/micr.30514.
    1. von Elm E, et al. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. BMJ. 2007;335:806–808. doi: 10.1136/.
    1. Efficace F, et al. Beyond the development of health-related quality-of-life (HRQOL) measures: a checklist for evaluating HRQOL outcomes in cancer clinical trials- Does HRQOL evaluation in prostate cancer research inform clinical decision making? J. Clin. Oncol. 2003;21:3502–3511. doi: 10.1200/JCO.2003.12.121.
    1. Brorson H, Höijer P. Standardised measurements used to order compression garments can be used to calculate arm volumes to evaluate lymphoedema treatment. J. Plast. Surg. Hand Surg. 2012;46:410–415. doi: 10.3109/2000656X.2012.714785.
    1. Jørgensen, M. G. et al. Adipose-derived regenerative cells and lipotransfer in alleviating breast cancer-related lymphedema: An open-label phase I trial with 4 years of follow-up. Stem Cells Transl. Med. 10.1002/sctm.20-0394 (2021).
    1. Executive Committee. The Diagnosis and Treatment of Peripheral Lymphedema: 2016 Consensus Document of the International Society of Lymphology. Lymphology. 2016;49:170–184.
    1. Harris PA, et al. Research electronic data capture (REDCap)–a metadata-driven methodology and workflow process for providing translational research informatics support. J. Biomed. Inform. 2009;42:377–381. doi: 10.1016/j.jbi.2008.08.010.
    1. Cornelissen AJM, et al. Quality of life questionnaires in breast cancer-related lymphedema patients: review of the literature. Lymphatic Res. Biol. 2018;16:134–139. doi: 10.1089/lrb.2017.0046.
    1. Grarup KR, Devoogdt N, Strand LI. The Danish version of Lymphoedema Functioning, Disability and Health Questionnaire (Lymph-ICF) for breast cancer survivors: translation and cultural adaptation followed by validity and reliability testing. Physiother. Theory Pract. 2019;35:327–340. doi: 10.1080/09593985.2018.1443186.
    1. Harrington S, Michener LA, Kendig T, Miale S, George SZ. Patient-reported upper extremity outcome measures used in breast cancer survivors: a systematic review. Arch. Phys. Med. Rehabil. 2014;95:153–162. doi: 10.1016/j.apmr.2013.07.022.
    1. Herup A, Merser S, Boeckstyns M. [Validation of questionnaire for conditions of the upper extremity] Ugeskr. Laege. 2010;172:3333–3336.
    1. Schønnemann JO, Larsen K, Hansen TB, Søballe K. Reliability and validity of the Danish version of the disabilities of arm, shoulder, and hand questionnaire in patients with fractured wrists. J. Plast. Surg. Hand Surg. 2011;45:35–39. doi: 10.3109/2000656X.2011.554708.
    1. Treanor C, Donnelly M. A methodological review of the Short Form Health Survey 36 (SF-36) and its derivatives among breast cancer survivors. Qual. Life Res. 2015;24:339–362. doi: 10.1007/s11136-014-0785-6.
    1. Bjorner JB, Thunedborg K, Kristensen TS, Modvig J, Bech P. The Danish SF-36 Health Survey: translation and preliminary validity studies. J. Clin. Epidemiol. 1998;51:991–999. doi: 10.1016/S0895-4356(98)00091-2.
    1. Bjorner JB, Kreiner S, Ware JE, Damsgaard MT, Bech P. Differential item functioning in the Danish translation of the SF-36. J. Clin. Epidemiol. 1998;51:1189–1202. doi: 10.1016/S0895-4356(98)00111-5.
    1. Bjorner JB, Damsgaard MT, Watt T, Groenvold M. Tests of data quality, scaling assumptions, and reliability of the Danish SF-36. J. Clin. Epidemiol. 1998;51:1001–1011. doi: 10.1016/S0895-4356(98)00092-4.
    1. Ochalek K, Partsch H, Gradalski T, Szygula Z. Do compression sleeves reduce the incidence of arm lymphedema and improve quality of life? Two-year results from a prospective randomized trial in breast cancer survivors. Lymphat. Res. Biol. 2019;17:70–77. doi: 10.1089/lrb.2018.0006.
    1. Osoba D, Rodrigues G, Myles J, Zee B, Pater J. Interpreting the significance of changes in health-related quality-of- life scores. J. Clin. Oncol. 1998;16:139–144. doi: 10.1200/JCO.1998.16.1.139.
    1. Qiu SS, et al. Outcomes following lymphaticovenous anastomosis (LVA) for 100 cases of lymphedema: results over 24-months follow-up. Breast Cancer Res. Treat. 2020;184:173–183. doi: 10.1007/s10549-020-05839-4.
    1. Jørgensen, M. G., Toyserkani, N. M., Hansen, F. G., Bygum, A. & Sørensen, J. A. Metadata record for the article: the impact of lymphedema on health-related quality of life up to 10 years after breast cancer treatment. figshare 10.6084/m9.figshare.14546208 (2021).

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe