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• W1981420381 abstract "Every year in the United States, breast cancer is diagnosed in more than 200,000 women. Because of the prevalence of breast cancer, treatment-related sequelae are of importance to many survivors of the disease. One such sequela is upper extremity lymphedema, which occurs when fluid accumulates in the interstitial space and causes enlargement and usually a feeling of heaviness in the limb. Axillary surgery contributes considerably to the incidence of lymphedema, with the incidence and severity of swelling related to the number of lymph nodes removed. Lymph-edema after standard axillary lymph node dissection can occur in up to approximately 50% of patients. However, the risk of lymph-edema is decreased substantially with newer sentinel lymph node sampling procedures. Adjuvant radiotherapy to the breast or lymph nodes increases the risk of lymphedema, which has been reported in 9% to 40% of these patients. Management of lymph-edema requires a multidisciplinary approach to minimize the effect on the patient's quality of life. This review presents an overview of the pathophysiology, diagnosis, prevention, and treatment of breast cancer-related lymphedema. Every year in the United States, breast cancer is diagnosed in more than 200,000 women. Because of the prevalence of breast cancer, treatment-related sequelae are of importance to many survivors of the disease. One such sequela is upper extremity lymphedema, which occurs when fluid accumulates in the interstitial space and causes enlargement and usually a feeling of heaviness in the limb. Axillary surgery contributes considerably to the incidence of lymphedema, with the incidence and severity of swelling related to the number of lymph nodes removed. Lymph-edema after standard axillary lymph node dissection can occur in up to approximately 50% of patients. However, the risk of lymph-edema is decreased substantially with newer sentinel lymph node sampling procedures. Adjuvant radiotherapy to the breast or lymph nodes increases the risk of lymphedema, which has been reported in 9% to 40% of these patients. Management of lymph-edema requires a multidisciplinary approach to minimize the effect on the patient's quality of life. This review presents an overview of the pathophysiology, diagnosis, prevention, and treatment of breast cancer-related lymphedema. Breast cancer is the most commonly diagnosed cancer in women and accounts for approximately 15% of all cancer deaths in women in the United States. In 2005, an estimated 211,000 women will receive a diagnosis of breast cancer, and an estimated 40,000 will die of the disease.1American Cancer Society Estimated new cancer cases for selected cancer sites by state, US, 2005. In: Cancer Facts & Figures 2005.Available at: www.cancer.org/docroot/MED/content/downloads/MED_1_1x_CFF2005_Estimated_New_Cases_Sites_by_State.aspGoogle Scholar2American Cancer Society Estimated cancer deaths for selected cancer sites by state, US, 2005. In: Cancer Facts & Figures 2005.Available at: www.cancer.org/docroot/MED/content/downloads/MED_1_1x_CFF2005_Estimated_Deaths_Sites_by_State.aspGoogle Scholar Breast cancer treatment includes surgery, radiotherapy, chemotherapy, and hormonal therapy. Although these treatments have improved patient outcomes, they have been associated with substantial adverse effects. Lymphedema, a sequela of breast cancer and breast cancer therapy, changes functional abilities and may affect a patient's psychosocial adjustment and overall quality of life. This review presents an overview of the pathophysiology, diagnosis, prevention, and treatment of breast cancer-related lymphedema. The lymphatic system is composed of superficial and deep lymphatic vessels that collect lymph from the skin, subcutaneous tissue, muscle, bone, and other structures. Lymph fluid consists of water, protein, cellular debris, toxins, and other macromolecules. The lymphatic system is designed to drain this fluid and return it to the intravascular circulation. Lymph fluid enters the interstitium, which increases oncotic pressure, thereby drawing water into the interstitium. When this drainage is compromised, fluid collects in the interstitial space, resulting in swelling. Lymphedema is the accumulation of lymph fluid in the interstitial space and may be secondary to infection, trauma, or congenital abnormalities. Fluid accumulation in the limbs causes enlargement, often with a feeling of heaviness.3Brennan MJ DePompolo RW Garden FH Focused review: postmastectomy lymphedema.Arch Phys Med Rehabil. 1996; 77: S74-S80Abstract Full Text PDF PubMed Google Scholar Chronic inflammation leads to fibrosis of the lymphatics, which compounds the problem.4Kobayashi MR Miller TA Lymphedema.Clin Plast Surg. 1987; 14: 303-313PubMed Google Scholar Lymphedema is classified as primary or secondary. Primary lymphedema is the rare result of a developmental abnormality of the lymphatic system manifesting either an early or late clinical presentation. These hereditary lymph-edemas include congenital lymphedema, lymphedema praecox, and lymphedema tarda.5Pipinos II Baxter TB The lymphatics.in: Townsend CM Beauchamp RD Evers BM Mattox KL Sabiston Textbook of Surgery. 17th ed. WB Saunders Co, Philadelphia, Pa2004: 2071-2079Google Scholar Secondary, or acquired, lymphedema is the most common lymphedema worldwide, with a total incidence of more than 100 million cases.6World Health Organization Lymphatic filariasis.Available at: www.who.int/mediacentre/factsheets/fs102/en/Date: September 2000Google Scholar Most of these cases are due to an infectious process such as filariasis. Other risk factors for acquired lymphedema include obesity, inflammation, trauma, and malignancy. Breast cancer-associated lymphedema can result from tumor compression or lymphatic vessel obstruction but is caused more commonly by breast cancer therapy such as surgery and radiotherapy.7Petropoulos P Lymphedema.in: Ferri FF Ferri's Clinical Advisor: Instant Diagnosis and Treatment. Mosby, St Louis, Mo2005: 490-491Google Scholar Sentinel lymph node (SLN) mapping studies have confirmed the presence of 3 interconnecting lymphatic systems in the breast8Kern KA Achieving the lowest false-negative rate in peritumoral breast lymphatic mapping: the oncologic search for the Holy Grail.Ann Surg Oncol. 2003; 10: 486-487Crossref PubMed Scopus (2) Google Scholar9Nathanson SD Wachna DL Gilman D Karvelis K Havstad S Ferrara J Pathways of lymphatic drainage from the breast.Ann Surg Oncol. 2001; 8: 837-843Crossref PubMed Google Scholar—the dermal, subcutaneous, and parenchymal lymphatics, which travel along the routes of the breast's blood supply to the regional lymphatics. The primary drainage is to the axilla, with only a small proportion of the lymph draining to extra-axillary sites (internal mammary, infraclavicular, and supraclavicular lymph nodes). Metastatic spread to the axilla occurs in approximately 30% of patients with breast cancer and is the strongest prognostic factor in breast cancer.10Chang JC Hilsenbeck SG Prognostic and predictive markers.in: Harris JR Lippman ME Morrow M Osborne CK Diseases of the Breast. 3rd ed. Lippincott Williams & Wilkins, Philadelphia, Pa2004: 675-696Google Scholar Lymph node status is the most powerful predictor of survival in patients with breast cancer.11Woodward WA Strom EA Tucker SL et al.Changes in the 2003 American Joint Committee on Cancer staging for breast cancer dramatically affect stage-specific survival.J Clin Oncol. 2003; 21: 3244-3248Crossref PubMed Scopus (118) Google Scholar The most recent Surveillance, Epidemiology, and End Results Program data showed a 29% incidence of regional lymph node metastases at the time of breast cancer diagnosis.12Ries LAG Eisner MP Kosary CL SEER Cancer Statistics Review, 1975-2000. National Cancer Institute, Bethesda, Md2003Google Scholar Although lymph node status is important for prognosis, it also provides information to determine the necessity and methods of further treatment such as chemotherapy, hormonal therapy, or radiotherapy. Surgical removal of the lymph nodes may improve locoregional control by decreasing the risk of axillary nodal failure. Surgical evaluation of the axilla has been accomplished traditionally by axillary lymph node dissection (ALND) in which level I and level II lymph nodes were removed. This procedure can be associated with substantial morbidities, such as pain, numbness, decreased range of motion of the shoulder, injury to the axillary vein, seroma formation, infection, and lymphedema.13Pressman PI Surgical treatment and lymphedema.Cancer. 1998; 83: 2782-2787Crossref PubMed Google Scholar To help minimize the adverse effects of these potential morbidities, newer surgical techniques such as lymphatic mapping and sentinel lymphadenectomy are being performed increasingly. Lymphatic mapping with SLN biopsy is performed to stage the axilla, as is done in standard axillary dissections. The procedure involves the identification and removal of the first lymph node(s), called the SLN(s), to receive lymphatic drainage from the breast parenchyma and tumor. This procedure, first used in patients with melanoma, is accepted for the evaluation of clinically occult lymph node metastasis (staging the axilla) in stage I and stage II breast cancer. If performed by an experienced surgeon, the false-negative rate for SLN biopsies is 12% or less.14Liberman L Cody III, HS Hill AD et al.Sentinel lymph node biopsy after percutaneous diagnosis of nonpalpable breast cancer.Radiology. 1999; 211: 835-844Crossref PubMed Scopus (44) Google Scholar15Kelley MC Hansen N McMasters KM Lymphatic mapping and sentinel lymphadenectomy for breast cancer.Am J Surg. 2004; 188: 49-61Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar With ALND, many studies have shown a correlation between the number of lymph nodes removed and the severity of the lymphedema.16Querci 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: 158-161Crossref PubMed Scopus (60) Google Scholar, 17Engel J Kerr J Schlesinger-Raab A Sauer H Holzel D Axilla surgery severely affects quality of life: results of a 5-year prospective study in breast cancer patients [published correction appears in Breast Cancer Res Treat. 2003;80:233].Breast Cancer Res Treat. 2003; 79: 47-57Crossref PubMed Scopus (142) Google Scholar, 18Schrenk P Rieger R Shamiyeh A Wayand W Morbidity following sentinel lymph node biopsy versus axillary lymph node dissection for patients with breast carcinoma.Cancer. 2000; 88: 608-614Crossref PubMed Scopus (475) Google Scholar, 19Kissin MW Querci della Rovere G Easton D Westbury G Risk of lymphoedema following the treatment of breast cancer.Br J Surg. 1986; 73: 580-584Crossref PubMed Scopus (611) Google Scholar, 20Herd-Smith A Russo A Muraca MG Del Turco MR Cardona G Prognostic factors for lymphedema after primary treatment of breast carcinoma.Cancer. 2001; 92: 1783-1787Crossref PubMed Scopus (149) Google Scholar These series have reported various rates of lymphedema for axillary sampling, partial lymphadenectomy, and total axillary lymphadenectomy. The reported incidence of lymphedema after standard axillary dissection can be as high as 56%.19Kissin MW Querci della Rovere G Easton D Westbury G Risk of lymphoedema following the treatment of breast cancer.Br J Surg. 1986; 73: 580-584Crossref PubMed Scopus (611) Google Scholar21Erickson VS Pearson ML Ganz PA Adams J Kahn KL Arm edema in breast cancer patients.J Natl Cancer Inst. 2001; 93: 96-111Crossref PubMed Scopus (454) Google Scholar22Gerber L Lampert M Wood C et al.Comparison of pain, motion, and edema after modified radical mastectomy vs. local excision with axillary dissection and radiation.Breast Cancer Res Treat. 1992; 21: 139-145Crossref PubMed Scopus (96) Google Scholar Current literature suggests that lymphatic mapping with SLN biopsy accurately stages the axilla and decreases the morbidity associated with ALND.18Schrenk P Rieger R Shamiyeh A Wayand W Morbidity following sentinel lymph node biopsy versus axillary lymph node dissection for patients with breast carcinoma.Cancer. 2000; 88: 608-614Crossref PubMed Scopus (475) Google Scholar23Blanchard DK Donohue JH Reynolds C Grant CS Relapse and morbidity in patients undergoing sentinel lymph node biopsy alone or with axillary dissection for breast cancer.Arch Surg. 2003; 138: 482-487Crossref PubMed Scopus (231) Google Scholar24Schijven MP Vingerhoets AJ Rutten HJ et al.Comparison of morbidity between axillary lymph node dissection and sentinel node biopsy.Eur J Surg Oncol. 2003; 29: 341-350Abstract Full Text PDF PubMed Scopus (217) Google Scholar In retrospective series comparing both techniques, the risk of lymphedema associated with SLN biopsy is less than that with ALND.18Schrenk P Rieger R Shamiyeh A Wayand W Morbidity following sentinel lymph node biopsy versus axillary lymph node dissection for patients with breast carcinoma.Cancer. 2000; 88: 608-614Crossref PubMed Scopus (475) Google Scholar23Blanchard DK Donohue JH Reynolds C Grant CS Relapse and morbidity in patients undergoing sentinel lymph node biopsy alone or with axillary dissection for breast cancer.Arch Surg. 2003; 138: 482-487Crossref PubMed Scopus (231) Google Scholar, 24Schijven MP Vingerhoets AJ Rutten HJ et al.Comparison of morbidity between axillary lymph node dissection and sentinel node biopsy.Eur J Surg Oncol. 2003; 29: 341-350Abstract Full Text PDF PubMed Scopus (217) Google Scholar, 25Goffman 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: 405-411Crossref PubMed Scopus (100) Google Scholar, 26Swenson KK Nissen MJ Ceronsky C Swenson L Lee MW Tuttle TM Comparison of side effects between sentinel lymph node and axillary lymph node dissection for breast cancer.Ann Surg Oncol. 2002; 9: 745-753Crossref PubMed Google Scholar, 27Burak WE Hollenbeck ST Zervos EE Hock KL Kemp LC Young DC Sentinel lymph node biopsy results in less postoperative morbidity compared with axillary lymph node dissection for breast cancer.Am J Surg. 2002; 183: 23-27Abstract Full Text Full Text PDF PubMed Scopus (211) Google Scholar, 28Haid A Kuehn T Konstantiniuk P et al.Shoulder-arm morbidity following axillary dissection and sentinel node only biopsy for breast cancer.Eur J Surg Oncol. 2002; 28: 705-710Abstract Full Text PDF PubMed Scopus (108) Google Scholar, 29Giuliano AE Haigh PI Brennan MB et al.Prospective observational study of sentinel lymphadenectomy without further axillary dissection in patients with sentinel node-negative breast cancer [published correction appears in J Clin Oncol. 2000;18:3877].J Clin Oncol. 2000; 18: 2553-2559Crossref PubMed Scopus (512) Google Scholar, 30Armer J Fu MR Wainstock JM Zagar E Jacobs LK Lymphedema following breast cancer treatment, including sentinel lymph node biopsy.Lymphology. 2004; 37: 73-91PubMed Google Scholar Lymphedema is decreased with SLN biopsy because fewer lymph nodes are removed and because no further axillary dissection is needed if the SLN findings are negative on pathologic analysis. A recent randomized trial of 298 patients with early-stage breast cancer assigned patients to undergo ALND or SLN biopsy followed by ALND if node results were positive. The findings of this study showed a significant decrease of 70% in the overall odds of lymphedema in patients undergoing SLN biopsy compared with those who underwent ALND (P=.004).31Purushotham AD Upponi S Klevensath MB et al.Morbidity after sentinel lymph node biopsy in primary breast cancer: results from a randomized controlled trial.J Clin Oncol. 2005; 23: 4312-4321Crossref PubMed Scopus (418) Google Scholar Lymphedema can be exacerbated by adjuvant radiotherapy. Patients with breast cancer typically receive adjuvant radiotherapy after breast-conservation surgery or mastectomy if there is a high chance of local or regional recurrence. Patients receiving radiotherapy can have breast or arm edema. When treatments are directed to the regional nodes, the risk of lymphedema is increased.20Herd-Smith A Russo A Muraca MG Del Turco MR Cardona G Prognostic factors for lymphedema after primary treatment of breast carcinoma.Cancer. 2001; 92: 1783-1787Crossref PubMed Scopus (149) Google Scholar32Ozaslan C Kuru B Lymphedema after treatment of breast cancer.Am J Surg. 2004; 187: 69-72Abstract Full Text Full Text PDF PubMed Scopus (191) Google Scholar Several studies have examined the incidence of lymphedema when axillary radiation is given after axillary dissection vs radiation to an undissected axilla. The risk of lymphedema is higher in women treated with axillary dissection and adjuvant radiation to the axilla, with edema reported in 9% to 40% of patients.19Kissin MW Querci della Rovere G Easton D Westbury G Risk of lymphoedema following the treatment of breast cancer.Br J Surg. 1986; 73: 580-584Crossref PubMed Scopus (611) Google Scholar Patients receiving radiotherapy to the axilla without ALND have a much lower risk of lymphedema.33Albrecht MR Zink K Busch W Ruhl U Dissection or irradiation of the axilla in postmenopausal patients with breast cancer: long-term results and long-term effects in 655 patients [in German].Strahlenther Onkol. 2002; 178: 510-516Crossref PubMed Scopus (19) Google Scholar, 34Coen JJ Taghian AG Kachnic LA Assaad SI Powell SN Risk of lymphedema after regional nodal irradiation with breast conservation therapy [published correction appears in Int J Radiat Oncol Biol Phys. 2003;56:604].Int J Radiat Oncol Biol Phys. 2003; 55: 1209-1215Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar, 35Meek AG Breast radiotherapy and lymphedema.Cancer. 1998; 83: 2788-2797Crossref PubMed Google Scholar Furthermore, the risk of lymphedema in patients who undergo breast surgery only, without axillary surgery or axillary radiation, is approximately 0%.35Meek AG Breast radiotherapy and lymphedema.Cancer. 1998; 83: 2788-2797Crossref PubMed Google Scholar The pathophysiology of radiation-induced lymphedema has not been established entirely but is believed to be related to fibrosis affecting the lymph nodes and causing constriction of lymphatic channels.35Meek AG Breast radiotherapy and lymphedema.Cancer. 1998; 83: 2788-2797Crossref PubMed Google Scholar Reports conflict regarding predisposing factors for the development of lymphedema after breast cancer treatment. Most of these reports have specifically examined patient age, weight, infection, preexisting cardiovascular conditions, and the surgical technique used.36Petrek JA Pressman PI Smith RA Lymphedema: current issues in research and management.CA Cancer J Clin. 2000; 50: 292-307Crossref PubMed Scopus (217) Google Scholar37Kocak Z Overgaard J Risk factors of arm lymphedema in breast cancer patients.Acta Oncol. 2000; 39: 389-392Crossref PubMed Scopus (73) Google Scholar Although published evidence shows a positive association with weight gain, number of nodes removed, tumor size, and surgical technique, several other investigators have not validated these findings.25Goffman 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: 405-411Crossref PubMed Scopus (100) Google Scholar38Petrek JA Senie RT Peters M Rosen PP Lymphedema in a cohort of breast carcinoma survivors 20 years after diagnosis.Cancer. 2001; 92: 1368-1377Crossref PubMed Scopus (549) Google Scholar Although the reported incidence of lymphedema varies with the clinical definition and methods of assessment, the incidence of lymphedema has been shown to increase each year after initial breast cancer treatment.38Petrek JA Senie RT Peters M Rosen PP Lymphedema in a cohort of breast carcinoma survivors 20 years after diagnosis.Cancer. 2001; 92: 1368-1377Crossref PubMed Scopus (549) Google Scholar39Geller BM Vacek PM O'Brien P Secker-Walker RH Factors associated with arm swelling after breast cancer surgery.J Womens Health (Larchmt). 2003; 12: 921-930Crossref PubMed Scopus (56) Google Scholar Patients with breast cancer and lymphedema may report symptoms such as a sensation of arm fullness and mild discomfort, which are seen in the early stages of the condition. Joint immobility, pain, and skin changes are noted frequently in the later stages of lymphedema. Patients also may be predisposed to infections involving the affected extremity. Diagnosis of lymphedema requires a detailed medical history and physical examination. Changes may include pitting of tissues, increased thickness of skin folds, and enlargement of the affected limb. Patients who have undergone breast cancer surgery can be taught to check for early signs of lymphedema by examining the arm and looking for changes in blood vessels and bony or tendon landmarks. Physical examination techniques include sequential circumferential measurements of the arm, water displacement volumetry, and tissue tonometry.40Gerber LH A review of measures of lymphedema.Cancer. 1998; 83: 2803-2804Crossref PubMed Google Scholar Circumferential arm measurement is used most frequently, although water displacement volumetry has been shown to be more accurate.36Petrek JA Pressman PI Smith RA Lymphedema: current issues in research and management.CA Cancer J Clin. 2000; 50: 292-307Crossref PubMed Scopus (217) Google Scholar Other quantitative measures involve radiological imaging studies such as computed tomography, magnetic resonance imaging, ultrasonography, lymphoscintigraphy, and lymphangiography. Both computed tomography and magnetic resonance imaging show a distinctive honeycomb pattern within the lymphatic system that helps differentiate lymphedema from other potential cancer-related causes of edema such as deep venous thrombosis.41Szuba A Rockson SG Lymphedema: classification, diagnosis and therapy.Vasc Med. 1998; 3: 145-156PubMed Google Scholar Lymphangiography was used extensively in the past as an imaging technique but is associated with inflammation, scarring, and atrophy that can affect the remaining lymphatic vessels; therefore, lymphoscintigraphy, which has not been associated with these problems, has become the gold standard. Lymphoscintigraphy uses a radiopharmaceutical such as technetium Tc 99m-filtered sulfur colloid to help determine functional and morphologic changes of the lymphatic system, which provides a qualitative and quantitative assessment of lymphedema. Lymphoscintigraphy has been shown to be the safest and most accepted method of diagnostic testing for lymphedema.21Erickson VS Pearson ML Ganz PA Adams J Kahn KL Arm edema in breast cancer patients.J Natl Cancer Inst. 2001; 93: 96-111Crossref PubMed Scopus (454) Google Scholar It is an effective tool that is most useful for diagnosing edema in patients with no known risk factors. It is also efficacious in distinguishing lymphedema from nonlymphatic causes of edema such as venous edema or lipedema.42Szuba A Shin WS Strauss HW Rockson S The third circulation: radionuclide lymphoscintigraphy in the evaluation of lymphedema.J Nucl Med. 2003; 44: 43-57PubMed Google Scholar The specific advantage of lymphoscintigraphy is that it can identify pathways of lymphatic drainage, dermal backflow, collateral lymph channels, number of lymph nodes, and clearance times of the radiopharmaceutical.43Kramer EL Lymphoscintigraphy: defining a clinical role.Lymphat Res Biol. 2004; 2: 32-37Crossref PubMed Scopus (29) Google Scholar, 44Stanton AW Mellor RH Cook GJ et al.Impairment of lymph drainage in subfascial compartment of forearm in breast cancer-related lymphedema.Lymphat Res Biol. 2003; 1: 121-132Crossref PubMed Scopus (53) Google Scholar, 45Bourgeois P Leduc O Leduc A Imaging techniques in the management and prevention of posttherapeutic upper limb edemas.Cancer. 1998; 83: 2805-2813Crossref PubMed Google Scholar Also, changes can be seen with lymphoscintigraphy that can aid in assessing the results of therapeutic interventions. The sensitivity of this technique reportedly ranges from 73% to 97% with a specificity of 100%.46Tiwari A Cheng KS Button M Myint F Hamilton G Differential diagnosis, investigation, and current treatment of lower limb lymphedema.Arch Surg. 2003; 138: 152-161Crossref PubMed Scopus (191) Google Scholar47Ter SE Alavi A Kim CK Merli G Lymphoscintigraphy: a reliable test for the diagnosis of lymphedema.Clin Nucl Med. 1993; 18: 646-654Crossref PubMed Scopus (85) Google Scholar However, results vary among clinical centers because there is no specific protocol for lymphoscintigraphy regarding type of radioactive tracer, site of injection, and use of static or dynamic images.15Kelley MC Hansen N McMasters KM Lymphatic mapping and sentinel lymphadenectomy for breast cancer.Am J Surg. 2004; 188: 49-61Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar A staging system has been developed for lymphedema (Table 1). Many clinicians have defined clinically significant lymphedema as a difference in circumference of greater than 2 cm between the extremities.21Erickson VS Pearson ML Ganz PA Adams J Kahn KL Arm edema in breast cancer patients.J Natl Cancer Inst. 2001; 93: 96-111Crossref PubMed Scopus (454) Google Scholar36Petrek JA Pressman PI Smith RA Lymphedema: current issues in research and management.CA Cancer J Clin. 2000; 50: 292-307Crossref PubMed Scopus (217) Google Scholar48Petrek JA Heelan MC Incidence of breast carcinoma-related lymphedema.Cancer. 1998; 83: 2776-2781Crossref PubMed Google Scholar49Harris SR Hugi MR Olivotto IA Levine M Steering Committee for Clinical Practice Guidelines for the Care and Treatment of Breast Cancer Clinical practice guidelines of the care and treatment of breast cancer, 11: lymphedema.CMAJ. 2001; 164: 191-199PubMed Google Scholar However, most clinical trials have used volume-based rating scales to assess edema. Other parameters that have been used to determine the stage of lymphedema include limb circumference, tissue texture, dermal changes, subjective sensations, and tissue responses to gravity or pressure.50Cheville AL McGarvey CL Petrek JA Russo SA Thiadens SR Taylor ME The grading of lymphedema in oncology clinical trials.Semin Radiat Oncol. 2003; 13: 214-225Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar Subjective reporting based on patient questionnaires also is used, but patients’ assessments can be limited by other factors such as weight gain or inherent muscle differences between the extremities. Currently, attempts are under way to develop 1 set of criteria that can be used by all investigators to grade lymphedema in future epidemiological trials.50Cheville AL McGarvey CL Petrek JA Russo SA Thiadens SR Taylor ME The grading of lymphedema in oncology clinical trials.Semin Radiat Oncol. 2003; 13: 214-225Abstract Full Text Full Text PDF PubMed Scopus (122) Google ScholarTABLE 1Staging of LymphedemaStageDescriptionCharacteristicsIReversible lymphedema Swelling reduced with elevation of the swollen extremityPittingIISpontaneously irreversible lymphedema Increased fibrous tissue with progressive skin hardeningFrequent infectionsNo pittingNo reduction in swelling with elevation of the extremityIIILymphostatic elephantiasis Progressive fibrosclerosisSkin changes (large hanging skin folds, papillomas)Association with Stewart-Treves syndrome Open table in a new tab The treatment of lymphedema associated with breast cancer can include combined modality approaches, compression therapy, therapeutic exercises, and pharmacotherapy. One of the most common forms of treatment consists of a multimodality approach called complex decongestive physiotherapy. This therapy involves various techniques such as manual lymphatic drainage, external compression devices, and exercises administered by well-trained therapists. Complex decongestive physiotherapy (also known as comprehensive decongestive treatment, complete decongestive physiotherapy, and multimodal physical therapy) includes 2 phases. In phase I, acute management is in an outpatient clinic setting. On average, it consists of a 4-week program of manual lymphatic drainage, short-stretch compression bandaging, exercise, and proper skin and nail care. Specifically, manual lymphatic drainage uses light massage strokes that first stimulate the functioning lymph vessels in the trunk and contralateral arm and then, working from the proximal to distal aspect, pushes the stagnant fluid from the edematous arm. Manual lymphatic drainage also stimulates the contractility of the lymphatic system to help with protein transport and the breaking up of fibrotic tissue.51Lerner R What's new in lymphedema therapy in America?.Int J Angiol. 1998; 7: 191-196Crossref PubMed Scopus (16) Google Scholar These techniques usually are performed by physical therapists who have been well trained specifically in these treatment approaches. The specialized massage techniques require about 45 minutes for each extremity.52Cheville AL McGarvey CL Petrek JA Russo SA Taylor ME Thiadens SR Lymphedema management.Semin Radiat Oncol. 2003; 13: 290-301Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar Several studies have shown a greater than 50% volume reduction of the affected limb in patients who undergo complex decongestive physiotherapy.21Erickson VS Pearson ML Ganz PA Adams J Kahn KL Arm edema in breast cancer patients.J Natl Cancer Inst. 2001; 93: 96-111Crossref PubMed Scopus (454) Google Scholar Phase II, maintenance at home by the patient or family, involves continued proper skin care and exercise, self-massage, and use of a compression sleeve and glove during the day and bandaging at night. Compression therapy includes compression bandages, compression garments, gradient compression devices, or pneumatic compression devices to mobilize the lymph fluid. Compression pumps typically are used daily for 30 minutes to several hours and should be used in addition to other forms of manual treatment. Caution must be used with these pumps because of potential damage to the vasculature. In patients with congestive heart failure, active infection, or deep venous thrombosis, pneumatic compression devices are contraindicated.53Rockson SG Miller LT Senie R American Cancer Society Lymphedema Workshop et al.Workgroup III: diagnosis and management of lymphedema.Cancer. 1998; 83: 2882-2885Crossref PubMed Google Scholar Recent data, primarily showing the lack of improvement in the edematous extremity,54Lerner R Complete decongestive physiotherapy and the Lerner Lymphedema Services Academy of Lymphatic Studies (the Lerner School).Cancer. 1998; 83: 2861-2863Crossref PubMed Google Scholar also suggest that pumps are not as efficacious as other treatment methods. Furthermore, proper techniques must be used in applying these devices, which can be arduous for patients who have physical, psychosocial, or emotional difficulties.52Cheville AL McGarvey CL Petrek JA Russo SA Taylor ME Thiadens SR Lymphedema management.Semin Radiat Oncol. 2003; 13: 290-301Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar Therapeutic exercises are a recognized treatment of lymphedema. These include remedial exercises that aid lymph flow through repeated contraction and relaxation of muscles. These exercises should be individualized and should be performed while the edematous arm is bandaged. Ideally, these exercises are initiated by well-trained therapists and then continued at home. Pharmacological interventions to treat lymphedema include antibiotics for treatment of infections, benzopyrones, flavonoids, diuretics, hyaluronidase, pantothenic acid, and selenium.55Casley-Smith JR Morgan RG Piller NB Treatment of lymphedema of the arms and legs with 5,6-benzo-[alpha]-pyrone.N Engl J Med. 1993; 329: 1158-1163Crossref PubMed Scopus (251) Google Scholar Benzopyrones, although not approved by the US Food and Drug Administration, have been used widely in Europe to treat lymphedema. Coumarin is 1 drug in this class that has been used extensively. In a study by Casley-Smith et al,55Casley-Smith JR Morgan RG Piller NB Treatment of lymphedema of the arms and legs with 5,6-benzo-[alpha]-pyrone.N Engl J Med. 1993; 329: 1158-1163Crossref PubMed Scopus (251) Google Scholar coumarin was given in a randomized, double-blind, placebo-controlled study to determine whether it decreased lymphedema. A total of 31 patients with edema from breast cancer treatment received 400 mg of coumarin (18 patients) or placebo (13 patients) for 6 months. The authors noted a significant decrease in the mean amount of edema fluid in the upper extremities of patients receiving coumarin. However, Loprinzi et al56Loprinzi CL Kugler JW Sloan JA et al.Lack of effect of coumarin in women with lymphedema after treatment for breast cancer.N Engl J Med. 1999; 340: 346-350Crossref PubMed Scopus (148) Google Scholar found no significant difference in arm volumes at 6 and 12 months in 140 patients with breast cancer treated with 200 mg of oral coumarin twice daily for 6 months. Diuretics have shown no significant benefit in the treatment of lymphedema.57Kligman L Wong RK Johnston M Laetsch NS The treatment of lymphedema related to breast cancer: a systematic review and evidence summary.Support Care Cancer. June 2004; 12: 421-431Crossref PubMed Scopus (85) Google Scholar Selenium has been shown to be effective in improving radiation-induced secondary lymphedema.58Bruns F Micke O Bremer M Current status of selenium and other treatments for secondary lymphedema.J Support Oncol. 2003; 1: 121-130PubMed Google Scholar This was confirmed in a small study by Micke et al59Micke O Bruns F Mucke R et al.Selenium in the treatment of radiation-associated secondary lymphedema.Int J Radiat Oncol Biol Phys. 2003; 56: 40-49Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar in which arm circumference decreased in 83% of patients (10 of 12) after administration of selenium. No toxicities were observed with selenium use in this setting, although nausea, vomiting, diarrhea, and tachycardia are documented adverse effects.60Subcommittee on Selenium, Committee on Animal Nutrition, Board on Agriculture, National Research Council Effects of excess selenium.in: Selenium in Nutrition. Revised ed. National Academy Press, Washington, DC1983: 107-113Google Scholar Further validation of the efficacy and tolerability of selenium in this setting should be performed in a larger trial setting. Lymphedema is a chronic and debilitating disease that can arise from breast cancer treatment. It generally is under-reported and undertreated. The effects of lymphedema on a patient's quality of life are substantial and can be devastating. Further education and better clinical trials are needed to address the importance of early recognition and treatment of lymphedema after breast cancer." @default.
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