Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Systematic Review Article

Breast Cancer-related Lymphedema: Recent Updates on Clinical Efficacy of Therapies and Bioengineering Approaches for a Personalized Therapy

Author(s): Xinliang Zhang, Narasimha M. Beeraka, Mikhail Y. Sinelnikov, Oleg S. Glazachev, Konstantin S. Ternovoy, Pengwei Lu, Aida Isaeva, Yu Cao, Jin Zhang, Arshia Bakhtiari Nezhad, Maria Plotnikova and Kuo Chen*

Volume 30, Issue 1, 2024

Published on: 21 December, 2023

Page: [63 - 70] Pages: 8

DOI: 10.2174/0113816128269545231218075040

Price: $65

Open Access Journals Promotions 2
Abstract

Background: Post-mastectomy lymphedema is a chronic progressive disease characterized by a significant reduction in quality of life and a range of complications.

Aim: To this date, no single treatment method provides pathological correction of the mechanisms associated with tissue reorganization observed in later-stage breast cancer-related lymphedema (BCRL).

Methods: To define a personalized approach to the management of patients with iatrogenic lymphedema, we performed a systematic review of literature without a comprehensive meta-analysis to outline existing molecular- genetic patterns, overview current treatment methods and their efficacy, and highlight the specific tissue-associated changes in BCRL conditions and other bio-engineering approaches to develop personalized therapy.

Results: Our results show that several tissue-specific and pathological molecular markers may be found, yet current research does not aim to define them.

Conclusion: As such, currently, a strong foundation for further research into molecular-genetic changes in lymphedema tissue exists, and further research should focus on finding specific targets for personalized treatment through bio-engineering approaches.

Keywords: Lymphedema, lymphatic system pathology, breast cancer, anti-BCRL therapies, bioengineering approaches, chronic progressive disease.

[1]
Chen K, Beeraka NM, Zhang X, et al. Recent advances in therapeutic modalities against breast cancer-related lymphedema: Future epigenetic landscape. Lymphat Res Biol 2023; lrb.2022.0016.
[http://dx.doi.org/10.1089/lrb.2022.0016] [PMID: 37267206]
[2]
Chen K, Zhang J, Beeraka NM, et al. Advances in the prevention and treatment of obesity-driven effects in breast cancers. Front Oncol 2022; 12: 820968.
[http://dx.doi.org/10.3389/fonc.2022.820968] [PMID: 35814391]
[3]
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(6): 500-15.
[http://dx.doi.org/10.1016/S1470-2045(13)70076-7] [PMID: 23540561]
[4]
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(7): 1959-72.
[http://dx.doi.org/10.1245/s10434-009-0452-2] [PMID: 19365624]
[5]
Shah C, Vicini FA. Breast cancer-related arm lymphedema: Incidence rates, diagnostic techniques, optimal management and risk reduction strategies. Int J Radiat Oncol Biol Phys 2011; 81(4): 907-14.
[http://dx.doi.org/10.1016/j.ijrobp.2011.05.043]
[6]
Gillespie TC, Sayegh HE, Brunelle CL, Daniell KM, Taghian AG. Breast cancer-related lymphedema: Risk factors, precautionary measures, and treatments. Gland Surg 2018; 7(4): 379-403.
[http://dx.doi.org/10.21037/gs.2017.11.04] [PMID: 30175055]
[7]
Brix B, Sery O, Onorato A, Ure C, Roessler A, Goswami N. Biology of lymphedema. Biology 2021; 10(4): 261.
[http://dx.doi.org/10.3390/biology10040261] [PMID: 33806183]
[8]
McEvoy MP, Gomberawalla A, Smith M, et al. The prevention and treatment of breast cancer-related lymphedema: A review. Front Oncol 2022; 12: 1062472.
[http://dx.doi.org/10.3389/fonc.2022.1062472] [PMID: 36561522]
[9]
Schulze H, Nacke M, Gutenbrunner C, Hadamitzky C. Worldwide assessment of healthcare personnel dealing with lymphoedema. Health Econ Rev 2018; 8(1): 10.
[http://dx.doi.org/10.1186/s13561-018-0194-6] [PMID: 29663122]
[10]
Nurlaila I, Roh K, Yeom CH, Kang H, Lee S. Acquired lymphedema: Molecular contributors and future directions for developing intervention strategies. Front Pharmacol 2022; 13: 873650.
[http://dx.doi.org/10.3389/fphar.2022.873650] [PMID: 36386144]
[11]
Gebruers N, Verbelen H, De Vrieze T, Coeck D, Tjalma W. Incidence and time path of lymphedema in sentinel node negative breast cancer patients: A systematic review. Arch Phys Med Rehabil 2015; 96(6): 1131-9.
[http://dx.doi.org/10.1016/j.apmr.2015.01.014] [PMID: 25637862]
[12]
Peng X, Chen R, Rao Z, et al. High recurrence of lymphedema and influencing factors in discharged breast cancer patients during the COVID-19 pandemic: A multicenter, cross-sectional survey. Cancer Med 2022; 11(19): 3572-80.
[http://dx.doi.org/10.1002/cam4.4737] [PMID: 35543195]
[13]
Trinh XT, Chien PN, Long NV, et al. Development of predictive models for lymphedema by using blood tests and therapy data. Sci Rep 2023; 13(1): 19720.
[http://dx.doi.org/10.1038/s41598-023-46567-1] [PMID: 37957217]
[14]
Jang S, Lee CU, Hesley GK, Knudsen JM, Brinkman NJ, Tran NV. Lymphatic mapping using US microbubbles before lymphaticovenous anastomosis surgery for lymphedema. Radiology 2022; 304(1): 218-24.
[http://dx.doi.org/10.1148/radiol.212351] [PMID: 35380494]
[15]
Cheng M-H, Chang DW, Patel KM. Principles and practice of lymphedema surgery. Elsevier Health Sciences 2021.
[16]
Pons G, Masia J, Loschi P, Nardulli ML, Duch J. A case of donor-site lymphoedema after lymph node–superficial circumflex iliac artery perforator flap transfer. J Plast Reconstr Aesthet Surg 2014; 67(1): 119-23.
[http://dx.doi.org/10.1016/j.bjps.2013.06.005] [PMID: 23827445]
[17]
Engel H, Lin CY, Huang JJ, Cheng MH. Outcomes of lymphedema microsurgery for breast cancer-related lymphedema with or without microvascular breast reconstruction. Ann Surg 2018; 268(6): 1076-83.
[http://dx.doi.org/10.1097/SLA.0000000000002322] [PMID: 28594742]
[18]
Ito R, Wu CT, Lin MCY, Cheng MH. Successful treatment of early-stage lower extremity lymphedema with side-to-end lymphovenous anastomosis with indocyanine green lymphography assisted. Microsurgery 2016; 36(4): 310-5.
[http://dx.doi.org/10.1002/micr.30010] [PMID: 26666982]
[19]
Patel KM, Lin CY, Cheng MH. A prospective evaluation of lymphedema-specific quality-of-life outcomes following vascularized lymph node transfer. Ann Surg Oncol 2015; 22(7): 2424-30.
[http://dx.doi.org/10.1245/s10434-014-4276-3] [PMID: 25515196]
[20]
Cheng MH, Robles JA, Gozel Ulusal B, Wei FC. Reliability of zone IV in the deep inferior epigastric perforator flap: A single center’s experience with 74 cases. Breast 2006; 15(2): 158-66.
[http://dx.doi.org/10.1016/j.breast.2005.06.006] [PMID: 16061383]
[21]
Henry SL, Huang JJ, Cheng MH. Bilateral breast revision augmentation with deep inferior epigastric perforators/superficial inferior epigastric artery flaps: Case reports and literature review. Ann Plast Surg 2010; 64(4): 416-20.
[http://dx.doi.org/10.1097/SAP.0b013e3181b0224c] [PMID: 20224345]
[22]
Ali R, Bernier C, Lin YT, et al. Surgical strategies to salvage the venous compromised deep inferior epigastric perforator flap. Ann Plast Surg 2010; 65(4): 398-406.
[http://dx.doi.org/10.1097/SAP.0b013e3181d9ab27] [PMID: 20798623]
[23]
Chang CC, Huang JJ, Wu CW, et al. A strategic approach for DIEP flap breast reconstruction in patients with a vertical midline abdominal scar. Ann Plast Surg 2014; 73(Suppl. 1): S6-S11.
[http://dx.doi.org/10.1097/SAP.0000000000000244] [PMID: 25003447]
[24]
Saad A, Sadeghi A, Allen R. The anatomic basis of the profunda femoris artery perforator flap: A new option for autologous breast reconstruction-A cadaveric and computer tomography angiogram study. J Reconstr Microsurg 2012; 28(6): 381-6.
[http://dx.doi.org/10.1055/s-0032-1313773] [PMID: 22588791]
[25]
Ito R, Huang JJ, Wu JCW, Lin MCY, Cheng MH. The versatility of profunda femoral artery perforator flap for oncological reconstruction after cancer resection-Clinical cases and review of literature. J Surg Oncol 2016; 114(2): 193-201.
[http://dx.doi.org/10.1002/jso.24294] [PMID: 27377593]
[26]
Narushima M, Yamamoto T, Ogata F, Yoshimatsu H, Mihara M, Koshima I. Indocyanine green lymphography findings in limb lymphedema. J Reconstruct Microsurg 2016; 32(01): 72-9.
[27]
Mihara M, Hara H, Araki J, et al. Indocyanine green (ICG) lymphography is superior to lymphoscintigraphy for diagnostic imaging of early lymphedema of the upper limbs. PLoS One 2012; 7(6): e38182.
[http://dx.doi.org/10.1371/journal.pone.0038182] [PMID: 22675520]
[28]
Yamamoto T, Yamamoto N, Doi K, et al. Indocyanine green-enhanced lymphography for upper extremity lymphedema: A novel severity staging system using dermal backflow patterns. Plast Reconstr Surg 2011; 128(4): 941-7.
[http://dx.doi.org/10.1097/PRS.0b013e3182268cd9] [PMID: 21681123]
[29]
Cheng MH, Huang JJ, Wu CW, et al. The mechanism of vascularized lymph node transfer for lymphedema: Natural lymphaticovenous drainage. Plast Reconstr Surg 2014; 133(2): 192e-8e.
[http://dx.doi.org/10.1097/01.prs.0000437257.78327.5b] [PMID: 24469190]
[30]
Lin CH, Ali R, Chen SC, et al. Vascularized groin lymph node transfer using the wrist as a recipient site for management of postmastectomy upper extremity lymphedema. Plast Reconstr Surg 2009; 123(4): 1265-75.
[http://dx.doi.org/10.1097/PRS.0b013e31819e6529] [PMID: 19337095]
[31]
Pons G, Rodríguez-Bauzà E, Masià J. Barcelona lymphedema algorithm for surgical treatment in breast cancer–related lymphedema. J Reconstr Microsurg 2016; 32(5): 329-35.
[http://dx.doi.org/10.1055/s-0036-1578814] [PMID: 26975564]
[32]
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(6): 410-5.
[http://dx.doi.org/10.3109/2000656X.2012.714785] [PMID: 23157502]
[33]
International Society of Lymphology. The diagnosis and treatment of peripheral lymphedema. 2009 Concensus Document of the International Society of Lymphology. Lymphology 2009; 42(2): 51-60.
[PMID: 19725269]
[34]
Masia J, Kosutic D, Clavero JA, Larranaga J, Vives L, Pons G. Preoperative computed tomographic angiogram for deep inferior epigastric artery perforator flap breast reconstruction. J Reconstruct Microsurg 2010; 26(01): 21-8.
[http://dx.doi.org/10.1055/s-0029-1223854]
[35]
Klompenhouwer EG, Gobardhan PD, Beek MA, Voogd AC, Luiten EJT. The clinical relevance of axillary reverse mapping (ARM): Study protocol for a randomized controlled trial. Trials 2013; 14(1): 111.
[http://dx.doi.org/10.1186/1745-6215-14-111] [PMID: 23782712]
[36]
Dayan JH, Dayan E, Smith ML. Reverse lymphatic mapping: A new technique for maximizing safety in vascularized lymph node transfer. Plast Reconstr Surg 2015; 135(1): 277-85.
[http://dx.doi.org/10.1097/PRS.0000000000000822] [PMID: 25285683]
[37]
Yue T, Zhuang D, Zhou P, et al. A prospective study to assess the feasibility of axillary reverse mapping and evaluate its effect on preventing lymphedema in breast cancer patients. Clin Breast Cancer 2015; 15(4): 301-6.
[http://dx.doi.org/10.1016/j.clbc.2015.01.010] [PMID: 25776198]
[38]
Starritt EC, Joseph D, McKinnon JG, Lo SK, de Wilt JHW, Thompson JF. Lymphedema after complete axillary node dissection for melanoma: Assessment using a new, objective definition. Ann Surg 2004; 240(5): 866-74.
[http://dx.doi.org/10.1097/01.sla.0000143271.32568.2b] [PMID: 15492570]
[39]
Thompson M, Korourian S, Henry-Tillman R, et al. Axillary reverse mapping (ARM): A new concept to identify and enhance lymphatic preservation. Ann Surg Oncol 2007; 14(6): 1890-5.
[http://dx.doi.org/10.1245/s10434-007-9412-x] [PMID: 17479341]
[40]
Nos C, Lesieur B, Clough KB, Lecuru F. Blue dye injection in the arm in order to conserve the lymphatic drainage of the arm in breast cancer patients requiring an axillary dissection. Ann Surg Oncol 2007; 14(9): 2490-6.
[http://dx.doi.org/10.1245/s10434-007-9450-4] [PMID: 17549570]
[41]
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.
[http://dx.doi.org/10.1200/JCO.2006.07.4062] [PMID: 17485711]
[42]
Langer I, Guller U, Berclaz G, et al. Morbidity of sentinel lymph node biopsy (SLN) alone versus SLN and completion axillary lymph node dissection after breast cancer surgery: A prospective Swiss multicenter study on 659 patients. Ann Surg 2007; 245(3): 452-61.
[http://dx.doi.org/10.1097/01.sla.0000245472.47748.ec] [PMID: 17435553]
[43]
Bani HA, Fasching PA, Lux MM, et al. Lymphedema in breast cancer survivors: Assessment and information provision in a specialized breast unit. Patient Educ Couns 2007; 66(3): 311-8.
[http://dx.doi.org/10.1016/j.pec.2007.01.004] [PMID: 17331692]
[44]
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.
[http://dx.doi.org/10.1200/JCO.2008.16.3725] [PMID: 18838709]
[45]
Rubio IT, Cebrecos I, Peg V, et al. Extensive nodal involvement increases the positivity of blue nodes in the axillary reverse mapping procedure in patients with breast cancer. J Surg Oncol 2012; 106(1): 89-93.
[http://dx.doi.org/10.1002/jso.23048] [PMID: 22258666]
[46]
Bedrosian I, Babiera GV, Mittendorf EA, et al. A phase I study to assess the feasibility and oncologic safety of axillary reverse mapping in breast cancer patients. Cancer 2010; 116(11): 2543-8.
[http://dx.doi.org/10.1002/cncr.25096] [PMID: 20336790]
[47]
Ponzone R, Cont NT, Maggiorotto F, et al. Extensive nodal disease may impair axillary reverse mapping in patients with breast cancer. J Clin Oncol 2009; 27(33): 5547-51.
[http://dx.doi.org/10.1200/JCO.2009.22.1846] [PMID: 19826123]
[48]
Gobardhan PD, Wijsman JH, van Dalen T, et al. ARM: Axillary reverse mapping - The need for selection of patients. Eur J Surg Oncol 2012; 38(8): 657-61.
[http://dx.doi.org/10.1016/j.ejso.2012.04.012] [PMID: 22607749]
[49]
Khandelwal R, Poovamma CU, Shilpy C, Prema M, Anthony P. Axillary reverse mapping: Is it feasible in locally advanced breast cancer patients? Breast Dis 2014; 34(4): 151-5.
[http://dx.doi.org/10.3233/BD-140371] [PMID: 24934169]
[50]
Schunemann E Jr, Dória MT, Silvestre JBCH, Gasperin P Jr, Cavalcanti TCS, Budel VM. Prospective study evaluating oncological safety of axillary reverse mapping. Ann Surg Oncol 2014; 21(7): 2197-202.
[http://dx.doi.org/10.1245/s10434-014-3626-5] [PMID: 24599413]
[51]
Boneti C, Korourian S, Bland K, et al. Axillary reverse mapping: Mapping and preserving arm lymphatics may be important in preventing lymphedema during sentinel lymph node biopsy. J Am Coll Surg 2008; 206(5): 1038-42.
[http://dx.doi.org/10.1016/j.jamcollsurg.2007.12.022] [PMID: 18471751]
[52]
Ponzone R, Mininanni P, Cassina E, Sismondi P. Axillary reverse mapping in breast cancer: Can we spare what we find? Ann Surg Oncol 2008; 15(1): 390-1.
[http://dx.doi.org/10.1245/s10434-007-9663-6] [PMID: 17990039]
[53]
Nos C, Kaufmann G, Clough KB, et al. Combined axillary reverse mapping (ARM) technique for breast cancer patients requiring axillary dissection. Ann Surg Oncol 2008; 15(9): 2550-5.
[http://dx.doi.org/10.1245/s10434-008-0030-z] [PMID: 18618185]
[54]
Casabona F, Bogliolo S, Valenzano Menada M, Sala P, Villa G, Ferrero S. Feasibility of axillary reverse mapping during sentinel lymph node biopsy in breast cancer patients. Ann Surg Oncol 2009; 16(9): 2459-63.
[http://dx.doi.org/10.1245/s10434-009-0554-x] [PMID: 19506954]
[55]
Boneti C, Korourian S, Diaz Z, et al. Scientific Impact Award: Axillary reverse mapping (ARM) to identify and protect lymphatics draining the arm during axillary lymphadenectomy. Am J Surg 2009; 198(4): 482-7.
[http://dx.doi.org/10.1016/j.amjsurg.2009.06.008] [PMID: 19800452]
[56]
Tausch C, Baege A, Dietrich D, et al. Can axillary reverse mapping avoid lymphedema in node positive breast cancer patients? Eur J Surg Oncol 2013; 39(8): 880-6.
[http://dx.doi.org/10.1016/j.ejso.2013.05.009] [PMID: 23735162]
[57]
Deng H, Chen L, Jia W, et al. Safety study of axillary reverse mapping in the surgical treatment for breast cancer patients. J Cancer Res Clin Oncol 2011; 137(12): 1869-74.
[http://dx.doi.org/10.1007/s00432-011-1064-3] [PMID: 21935615]
[58]
Noguchi M. Axillary reverse mapping for breast cancer. Breast Cancer Res Treat 2010; 119(3): 529-35.
[http://dx.doi.org/10.1007/s10549-009-0578-8] [PMID: 19842033]
[59]
Gennaro M, Maccauro M, Sigari C, et al. Selective axillary dissection after axillary reverse mapping to prevent breast-cancer-related lymphoedema. Eur J Surg Oncol 2013; 39(12): 1341-5.
[http://dx.doi.org/10.1016/j.ejso.2013.09.022] [PMID: 24113621]
[60]
Han JW, Seo YJ, Choi JE, Kang SH, Bae YK, Lee SJ. The efficacy of arm node preserving surgery using axillary reverse mapping for preventing lymphedema in patients with breast cancer. J Breast Cancer 2012; 15(1): 91-7.
[http://dx.doi.org/10.4048/jbc.2012.15.1.91] [PMID: 22493634]
[61]
Jia W, Hitchcock-Szilagyi H, He W, Goldman J, Zhao F. Engineering the lymphatic network: A solution to lymphedema. Adv Healthc Mater 2021; 10(6): 2001537.
[http://dx.doi.org/10.1002/adhm.202001537] [PMID: 33502814]
[62]
Schaupper M, Jeltsch M, Rohringer S, Redl H, Holnthoner W. Lymphatic vessels in regenerative medicine and tissue engineering. Tissue Eng Part B Rev 2016; 22(5): 395-407.
[http://dx.doi.org/10.1089/ten.teb.2016.0034] [PMID: 27142568]
[63]
Alderfer L, Wei A, Hanjaya-Putra D. Lymphatic tissue engineering and regeneration. J Biol Eng 2018; 12(1): 32.
[http://dx.doi.org/10.1186/s13036-018-0122-7] [PMID: 30564284]
[64]
Asaad M, Hanson SE. Tissue engineering strategies for cancer-related lymphedema. Tissue Eng Part A 2021; 27(7-8): 489-99.
[http://dx.doi.org/10.1089/ten.tea.2020.0378] [PMID: 33563108]
[65]
Huethorst E, Krebber MM, Fledderus JO, et al. Lymphatic vascular regeneration: The next step in tissue engineering. Tissue Eng Part B Rev 2016; 22(1): 1-14.
[http://dx.doi.org/10.1089/ten.teb.2015.0231] [PMID: 26204330]
[66]
Chen K, Sinelnikov MY, Shchedrina MA, Mu L, Lu P. Surgical management of postmastectomy lymphedema and review of the literature. Ann Plast Surg 2021; 86(3S): S173-6.
[http://dx.doi.org/10.1097/SAP.0000000000002642] [PMID: 33346539]
[67]
Brennan MJ, Weitz J. Lymphedema 30 years after radical mastectomy. Am J Phys Med Rehabil 1992; 71(1): 12-4.
[http://dx.doi.org/10.1097/00002060-199202000-00004] [PMID: 1739437]
[68]
Azhar SH, Lim HY, Tan BK, Angeli V. The unresolved pathophysiology of lymphedema. Front Physiol 2020; 11: 137.
[http://dx.doi.org/10.3389/fphys.2020.00137] [PMID: 32256375]
[69]
Garner D, DeSnyder SM, Isales L, et al. Baseline inflammatory markers are associated with upper extremity lymphedema in breast cancer patients. Int J Radiat Oncol Biol Phys 2020; 108(3): e542-3.
[http://dx.doi.org/10.1016/j.ijrobp.2020.07.1692]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy