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Breast cancer-associated lymphedema

Breast cancer-associated lymphedema
Author:
Babak Mehrara, MD
Section Editors:
Daniel F Hayes, MD
Larissa Nekhlyudov, MD, MPH
Eduardo Bruera, MD
Patricia A Ganz, MD
Deputy Editors:
Kathryn A Collins, MD, PhD, FACS
Sadhna R Vora, MD
Literature review current through: Jun 2022. | This topic last updated: Apr 26, 2022.

INTRODUCTION — Lymphedema is defined as the interstitial collection of protein-rich fluid due to disruption of lymphatic flow. Lymphedema occurs when the lymphatic load exceeds the transport capacity of the lymphatic system, which causes filtered fluid to accumulate [1]. Lymphedema that occurs as the result of disease or treatments is called secondary lymphedema. Treatment of breast cancer (eg, surgery, radiation therapy) is one of the most common causes of secondary peripheral lymphedema. Surgical removal of lymph nodes (lymphadenectomy) and radiation therapy are the main cause of lymphedema in patients with breast cancer, but breast cancer-associated lymphedema (BCAL) can also occur due to obstruction of the lymphatic channels or lymph nodes, or infiltration with tumor cells (lymphangitic carcinomatosis).

Upper extremity lymphedema occurring in breast cancer patients, including risk factors, monitoring, prevention, and efficacy of lymphedema treatments, will be reviewed here. General considerations for the diagnosis and management of lymphedema that includes other etiologies, and surgical treatment of lymphedema, are reviewed elsewhere. (See "Clinical features and diagnosis of peripheral lymphedema" and "Clinical staging and conservative management of peripheral lymphedema" and "Surgical treatment of primary and secondary lymphedema".)

ANATOMY — In the upper extremity and chest wall, the superficial lymphatic system (lymphatic capillaries and precollectors) drains interstitial fluid from the skin and subcutaneous tissue into larger collecting vessels (ie, deep lymphatics). The deep lymphatics drain into the axillary lymph nodes where foreign material is filtered and where antigen-presenting cells interact with T and B cells to activate immune responses [1]. The lymphatics of the breast drain into the internal mammary nodes medially, and the axillary and supraclavicular nodes laterally and superiorly (figure 1). The lymph draining from the left upper body (upper extremity, chest wall, upper back, shoulder, and breast) enters the venous circulation through the thoracic duct, which opens into the venous angle between the left subclavian vein and left internal jugular vein (figure 2) [1]. The lymph draining from the right upper body drains into the right venous angle via the right lymphatic duct.

INCIDENCE AND RISK FACTORS — Breast cancer and its associated treatments are one of the most common causes of upper extremity lymphedema. In a systematic review that included 72 studies (29,612 women), the overall incidence of arm lymphedema in breast cancer survivors was 17 percent [2]. The incidence varied based on the mode of diagnosis; it was 13, 15, and 20 percent based on clinical information, formal measurement (eg, arm circumference), and self-assessment, respectively. (See "Clinical features and diagnosis of peripheral lymphedema", section on 'Diagnosis'.)

Risk factors — The main risk factors for breast cancer-associated lymphedema (BCAL) include invasive cancer diagnosis, dissection/disruption of axillary lymph nodes, radiation therapy, local infection, and obesity, but other factors may also contribute [3-5].

Axillary reverse mapping (ARM) may reduce the risk for lymphedema in patients undergoing sentinel lymph node biopsy or axillary lymph node dissection [6]. The manner and timing of breast reconstruction may also play a role in the development of lymphedema [7]. (See "Technique of axillary lymph node dissection", section on 'Axillary reverse mapping' and "Overview of breast reconstruction".)

Axillary node dissection — Lymphadenectomy is the primary cause of breast and upper extremity lymphedema in patients with breast cancer [1,2,4,8-14]. The incidence of lymphedema increases with increasing number of axillary nodes removed or disrupted [15]. In a systematic review, the incidence of lymphedema was approximately four times higher in women who had an axillary lymph node dissection compared with those who had sentinel node biopsy (19.9 versus 5.6 percent) [2]. Among patients who have undergone complete axillary node dissection, in one review, lymphedema developed in 23 percent when measured using limb volume and 45 percent using bioimpedance spectroscopy criteria [4]. Fortunately, contemporary surgical treatment of breast cancer does not automatically mandate axillary node dissection in women with clinically node-negative axilla. Instead, most women undergo sentinel lymph node biopsy, which is associated with a significantly lower risk of lymphedema compared with axillary node dissection (odds ratio [OR] 0.36, 95% CI 0.15-0.86) [16]. (See "Clinical features and diagnosis of peripheral lymphedema", section on 'Cancer and cancer treatment' and "Management of the regional lymph nodes in breast cancer" and "Overview of sentinel lymph node biopsy in breast cancer".)

Radiation therapy — Postoperative radiation therapy (breast, axilla, supraclavicular region) also increases the risk for lymphedema [17-22]. (See "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer".)

In a systematic review, the incidence of lymphedema was significantly higher among women who underwent surgery plus radiation therapy compared with surgery alone (41 versus 17 percent) [20]. Among women who have undergone axillary node dissection, radiation therapy is an additive risk factor. In one report, the incidence of subjective lymphedema with axillary node dissection alone and axillary node dissection plus radiation therapy were 7 and 38 percent, respectively [22].

Women undergoing breast-conserving therapy are also at risk for lymphedema following adjuvant radiation therapy [18,20]. A retrospective study involved 1497 women treated for breast cancer between 1980 and 2006 (75 percent with node-negative breast cancer) [18]. For the entire cohort, the reported incidence of lymphedema was 7 percent. For women treated with supraclavicular, axillary, or internal mammary radiation therapy, the incidences of lymphedema were 10, 15, and 8 percent, respectively.

Variations in the radiation therapy field design may impact the development of lymphedema. A retrospective study of 492 women treated for breast cancer showed that inclusion of level I and II axillary lymph nodes in the radiation field (ie, the radiation field included more than one third of the humoral head) significantly increased the risk of developing breast cancer-related lymphedema compared with patients in whom this area was excluded [23]. Women treated in this manner had a significantly greater increase in the incidence of lymphedema (37.1 versus 7.7 percent).

Other factors — Beyond lymphadenectomy and radiation therapy, the likelihood of developing lymphedema is related to increased body mass index or obesity [17,24]; postoperative infection, hematoma, or seroma; and possibly medication effects (eg, taxanes [25], longer duration of chemotherapy [26]). Weight gain is a contributory factor to the development of lymphedema [27]; obesity alone may impair lymphatic function and lead to the development of lymphedema [28]. (See "Clinical features and diagnosis of peripheral lymphedema", section on 'Obesity'.)

CLINICAL FEATURES, DIAGNOSIS, AND STAGING — Typical signs and symptoms of lymphedema include progressive upper extremity swelling, skin changes, limb pain and discomfort, restricted range of motion, and nonpitting edema. Restricted range of motion can be associated with the presence of thickened bands or cord of tissue [29]. Superficial phlebitis of the chest wall veins (Mondor disease) has also been associated with upper extremity lymphedema. (See "Clinical features and diagnosis of peripheral lymphedema", section on 'Clinical features'.)

Physical findings of asymmetric upper extremity measurements can usually establish a diagnosis of lymphedema. Methods to obtain clinical measurements are reviewed separately. (See "Clinical features and diagnosis of peripheral lymphedema", section on 'Diagnosis'.)

The differential diagnosis of lymphedema in patients with breast cancer includes other conditions associated with peripheral edema. Deep vein thrombosis related to central venous access is an important cause of upper extremity edema. Although central access is usually contralateral to the side of the breast surgery, particularly if there has been an axillary node dissection or axillary radiation, ipsilateral deep vein thrombosis can still occur. (See "Clinical features and diagnosis of peripheral lymphedema", section on 'Differential diagnosis' and "Catheter-related upper extremity venous thrombosis in adults".)

An onset of lymphedema several years after the primary surgery without obvious trauma should raise suspicion for tumor, which always needs to be evaluated. In particular, recurrence of the breast cancer in the axillary area or the development of lymphangiosarcoma should be excluded with breast imaging [30-32]. (See "Clinical staging and conservative management of peripheral lymphedema", section on 'Lymphangiosarcoma'.)

Clinical staging — Lymphedema is staged (International Society of Lymphology) based on the examination of the upper extremity and the volume difference between the extremities as stage 0 through stage III, which correspond to subclinical lymphedema, mild lymphedema, moderate lymphedema, and severe lymphedema [33]. (See "Clinical staging and conservative management of peripheral lymphedema", section on 'Clinical stage'.)

NATURAL HISTORY AND MONITORING — Following treatment for breast cancer, the onset of lymphedema is insidious and is typically characterized by slowly progressive swelling of the upper extremity ipsilateral to the axillary node dissection or radiation treatments [34].

At first, the swelling may be apparent only in the proximal portion of the limb, or it can affect only a portion of the distal limb including the digits. There may also be swelling over the ipsilateral breast and/or upper chest wall. In one systematic review, the greatest risk for developing upper extremity lymphedema was within the first two years following diagnosis and treatment [2]. However, the type of treatment appears to influence time course, and later onset can occur. In a study of over 2100 women who received surgery for breast cancer, early-onset lymphedema (<12 months postoperatively) was associated with axillary lymph node dissection (hazard ratio [HR] 4.8, 95% CI 2.6-8.8), while late-onset lymphedema (>12 months postoperatively) was associated with regional lymph node radiation (HR 3.9, 95% CI 2.0-7.4) and, to a lesser extent, axillary lymph node dissection (HR 1.9, 95% CI 1.1-3.2) [35]. The lymphedema risk peaked between 6 and 12 months in the axillary dissection without regional lymph node radiation group, between 18 and 24 months in the axillary dissection with regional lymph node radiation group, and between 36 and 48 months in the group receiving sentinel lymph node biopsy with regional lymph node radiation. On multivariate analysis, body mass index was also associated with lymphedema.

Early identification of those at risk for lymphedema (ISL stage 0) and protection measures in those with lymphedema (ISL stages I, II, III) may potentially keep lymphedema from progressing to a higher clinical stage; lymphedema is often difficult to treat if it progresses [36,37]. In a case-control study of 196 breast cancer patients, the application of a surveillance program that included preoperative limb volume measurement and interval postoperative follow-up was able to detect subclinical lymphedema (defined as a 3 percent difference in arm circumference), reduce affected limb volume with early treatment (with a compression sleeve and gauntlet), and maintain this volume reduction [38].

Measurements of arm circumference and/or volume are common methods for monitoring the onset and degree of lymphedema [4,33,39-41]. Other methods, such as measurements of bioimpedance spectroscopy, tissue compression (tonometry), and local tissue water, have also been investigated [42-45]. Clinical measurements are obtained initially to establish a baseline before breast cancer treatments and afterward at intervals to track changes during treatment. Alternatively, changes in arm circumference or volume relative to the contralateral normal limb can be performed. There is currently no consensus on how frequently these measurements should be performed, nor on the frequency of follow-up of women at risk for developing lymphedema. However, given that the highest risk of developing lymphedema is within the first three years of treatment and that early intervention can limit progression of disease, high-risk patients should be followed closely in this period (eg, every six months or if they develop symptoms). In addition, patients should be taught how to self-monitor. (See "Clinical features and diagnosis of peripheral lymphedema", section on 'Extremity measurements' and 'Primary prevention' below.)

PRIMARY PREVENTION — Primary prevention strategies aim to avoid the occurrence of lymphedema and promote patient well-being. For women with breast cancer, the only measure that effectively reduces the risk of developing lymphedema involves using sentinel lymph node biopsy for axillary lymph node staging rather than axillary node dissection. The role of lymph node reconstruction is under active investigation [46].

Breast cancer patients should monitor the ipsilateral limb, and among those with risk factors for lymphedema but without limb swelling (ie, ISL stage 0), other measures such as exercise/physiotherapy and compression therapy can be implemented early. However, these measures have not definitively been shown to prevent the occurrence of lymphedema at a later timeframe. (See 'Natural history and monitoring' above and 'Exercise, physiotherapy and compression' below.)

Blood pressure measurement, venipuncture, and peripheral intravenous line placement in the ipsilateral arm not affected by lymphedema has not been shown to affect the occurrence of lymphedema [46,47]. (See 'Risk factors' above and 'Unsupported risk reduction strategies' below.)

Limiting lymph node dissection — Limiting the extent of lymph node removal is the only measure shown to reduce the incidence of breast-cancer associated lymphedema. The use of axillary staging with sentinel node biopsy has reduced the number of axillary lymph node dissections performed and, consequently, the incidence of lymphedema [36]. Clinically relevant lymphedema occurs in 5 to 9 percent of patients who undergo sentinel node biopsy alone compared with approximately 40 percent in patients undergoing axillary lymph node dissection [2,48-51]. (See "Overview of sentinel lymph node biopsy in breast cancer".)

When lymph node dissection is necessary, other surgical techniques may also be effective for primary prevention, including minimizing the extent of lymph node dissection, reverse mapping, and lymphatic bypass [52-54]. Using advanced radiation therapy (RT) techniques that limit radiation may also be helpful.

Lymphatic reconstruction — Lymphovenous bypass (referred to as lymphatic microsurgical preventing healing approach [LYMPHA] or immediate lymphatic reconstruction [ILR]) can also be performed at the time of lymph node dissection to help prevent lymphedema [55]. In the largest series of 74 patients with an average follow-up of four years, only 4 percent of patients treated with LYMPHA developed lymphedema compared with historical rates of 15 to 65 percent [56]. Several centers have ongoing studies attempting to confirm the validity of these findings. (See "Surgical treatment of primary and secondary lymphedema".)

Exercise, physiotherapy and compression — Following treatment of breast cancer, range of motion exercises and compression sleeves are generally recommended for the affected arm [33,46,57-61]. (See "Clinical staging and conservative management of peripheral lymphedema", section on 'At risk for postoperative lymphedema'.)

Once any wounds have healed and provided there are no surgical complications that may interfere (eg, need for a drain), exercise and weight training should be encouraged. Properly fitted compression garments should be worn during exercise, including aerobic and resistance training. (See "Clinical staging and conservative management of peripheral lymphedema", section on 'Diet and exercise' and 'Compression therapy' below.)

For patients treated by axillary lymph node dissection, some trials, but not all, have supported physiotherapy (with or without manual lymphatic drainage) to improve arm mobility and potentially to prevent lymphedema [61-69].

In one trial, 116 women with unilateral axillary lymph node dissection were randomly assigned to education, early physiotherapy, and progressive active and action-assisted shoulder exercises, or to education alone [63]. After 12 months of follow-up, significantly fewer women treated with prophylactic physiotherapy developed lymphedema (7 versus 25 percent with education alone).

In another trial involving 67 women who underwent surgery for breast cancer, patients were randomly assigned to a six-month course of physiotherapy starting on postoperative day 2, or no physiotherapy [68]. At the six-month postoperative reassessment, there was no increase in arm volume among women who underwent physiotherapy; women who did not undergo physiotherapy had a significant increase in upper extremity volume.

By contrast, in a trial that randomly assigned 158 patients age 18 to 75 years to progressive resistance training (early supervised/later unsupervised) or usual care, arm volume or lymphedema incidence at one year were not significantly different between the groups [69].

Unsupported risk reduction strategies — Other measures have commonly been used in postoperative patients who do not exhibit lymphedema (ie, ISL stage 0), but which have not been shown to alter the development of lymphedema or complications following breast cancer surgery. These include avoiding intravenous catheter placement, venipuncture, and blood pressure measurements in the ipsilateral extremity [70,71]. This issue remains a significant concern in the anesthetic management of patients with breast cancer undergoing intervention. While the International Society of Lymphology noted that "while some precautions rest on solid physiological principles (eg, avoiding excessive heat on an at risk limb, not having chemotherapy administered into the limb unless medically necessary), others are less supported" [33]. In agreement with the American Society of Breast Surgeons [46], the Society for Ambulatory Anesthesia (SAMBA) issued a statement that intravenous catheter placement, venipuncture, and blood pressure measurements in the ipsilateral upper extremity are not contraindicated after breast surgery in patients who do not have lymphedema [47]. When fluid therapy and monitoring are required, we support a shared decision-making approach that accounts for the risk of developing lymphedema (lymph node dissection versus sentinel lymph node biopsy, radiation), the clinical situation and monitoring needs (eg, outpatient versus intensive care unit management), and patient preferences. When given a choice, many patients elect to use the contralateral arm [46].

Our approach is as follows:

For patients without significant risk factors for lymphedema (see 'Risk factors' above) and who do not have lymphedema, there is no need to avoid the ipsilateral extremity for intravenous catheter placement, venipuncture, and blood pressure measurements. One study prospectively investigated the association between factors thought to increase the risk for lymphedema in 632 patients treated for breast cancer and screened routinely for lymphedema [72]. On multivariate analysis, there was no significant association between increases in arm volume and blood pressure readings. Significant factors associated with the development of lymphedema included body mass index ≥25, axillary lymph node dissection, regional lymph node irradiation, and cellulitis. There was also no association between blood pressure readings on the ipsilateral arm and cellulitis.

Whether to avoid ipsilateral blood pressure measurement, venipuncture, and peripheral intravenous line placement in patients with significant risk factors for the development of lymphedema (see 'Risk factors' above) but who do not have lymphedema is controversial. We prefer not to use the ipsilateral extremity when another option is available.

LYMPHEDEMA MANAGEMENT

Protection of the affected extremity — For patients with lymphedema, ongoing monitoring and measures to protect the extremity are aimed at minimizing the degree of edema, slowing the rate of lymphedema progression, and preventing complications [62,71,73-76]. These are listed below and reviewed in more detail elsewhere. (See "Clinical staging and conservative management of peripheral lymphedema", section on 'General measures'.)

Patients with lymphedema should be encouraged to:

Monitor their extremity, including taking upper limb measurements. Measurements should be taken at the metacarpal-phalangeal joints (if edematous), around the wrist, 10 cm below to the olecranon process, and 10 cm above to the olecranon process. The patient should report any changes in size, sensation, color, temperature, or skin condition. In a review of 100 women, perceived swelling and differences in tissue texture between the arm was associated with, and sensitive to, bioimpedance spectroscopy-detected lymphedema [77]. (See "Clinical features and diagnosis of peripheral lymphedema", section on 'Extremity measurements' and 'Natural history and monitoring' above.)

Maintain meticulous skin hygiene and nail care to prevent a portal of entry for infection that may result in cellulitis. Use skin moisturizers and treat small breaks in the skin, as may be induced by a paper cut or abrasions, pinpricks, insect bites, or pet scratches, with topical antibiotics. Protect exposed skin using sunscreen and wear gloves when participating in activities that could lead to skin injury.

Seek medical attention and treatment for any clinical signs that could represent an episodes of cellulitis. (See "Cellulitis and skin abscess: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

Elevate the extremity when able. Simple elevation may reduce swelling, particularly in the early stage of lymphedema [78].

Continue to exercise. Upper body exercise is safe in women treated by axillary lymph node dissection [63,68,69,79-92]. In a systematic review, a significant reduction of lymphedema was documented by bioimpedance spectroscopy values in response to resistance exercise [58].

Wear properly fitted graded compression sleeves, which can reduce the degree of lymphedema. (See 'Compression therapy' below.)

Avoid procedures that puncture the skin of the lymphedematous arm (eg, vaccination, acupuncture, phlebotomy, intravenous lines, venography). When needed, these can be performed in the contralateral arm [93]. (See "Clinical staging and conservative management of peripheral lymphedema", section on 'Avoid skin infection/injury'.)

Maintain ideal body weight [37]. In addition to increasing the risk for breast-cancer associated lymphedema, obesity may also limit the effectiveness of compression pumps or sleeves.

Blood pressure measurement — For patients with lymphedema (ie, ISL stage I, II, III), we support a recommendation to measure blood pressure in the contralateral arm, particularly in any setting in which blood pressure is being closely repeatedly or continuously monitored (eg, in an intensive care unit, recovery room, or during procedures). This recommendation is based upon several factors. Blood pressure measurement in an enlarged extremity will be inaccurate if the cuff is not properly sized and the cuff causes a high-pressure focal compression (in contrast to pneumatic compression devices used for lymphedema treatment, for which the compression is applied sequentially) [70,71]. Among the rare patient who has undergone bilateral axillary lymph node dissection and has bilateral lymphedema, routine blood pressure measurements can be obtained in the lower extremity. If the patient has had bilateral axillary lymph node dissection and there is not an option of obtaining blood pressure measurements in the lower extremity, then a manual (but not automatic) blood pressure cuff can be used intermittently, but inflated to only just above the expected level of systolic blood pressure [70]. (See "Blood pressure measurement in the diagnosis and management of hypertension in adults", section on 'Leg blood pressure'.)

Care during travel — Although in theory lymphedema may be exacerbated at high altitude or during air travel, since the ambient atmosphere pressure is less than the relative outlet transcapillary pressure within the superficial tissues, studies suggest that the risk from air travel of precipitating or worsening lymphedema is low [94-96]. The use of compression sleeves during air flight in women with lymphedema is debated. Some suggest that domestic air travel (<4.5 hours) is low risk and that compression devices may be counterproductive [97]. For longer-duration air travel, compression garments, exercises, and self-massage may all be helpful. (See 'Compression therapy' below.)

Effectiveness of conservative treatments — Untreated, the degree of lymphedema increases over time [98]. Early, consistent, and ongoing treatment is necessary to limit the amount of extremity swelling. The conservative treatment of established lymphedema consists of a multimodality regimen that includes general self-care measures (exercise, skin care), compression therapy (compression bandaging, compression garments, intermittent pneumatic compression), and physiotherapy (eg, simple lymphatic drainage, manual lymphatic drainage, complete decongestive therapy), the type and the intensity of which depend upon the clinical stage [33,46,99-101]. (See "Clinical staging and conservative management of peripheral lymphedema", section on 'Conservative treatment by severity'.)

The effectiveness of these treatments in patients with established breast cancer-associated lymphedema (BCAL) is summarized below.

For patients with mild lymphedema (ISL stage I), we suggest physiotherapy in the form of manual lymphatic drainage and compression garments, rather than more intensive therapy. Manual lymphatic drainage (MLD) is a massage-like technique that is typically performed by specially trained physical therapists, but a self-help maneuver (simple lymphatic drainage) has also been used for mild cases. Light pressure is used to mobilize edema fluid from distal to proximal areas. (See 'Manual lymphatic drainage' below.)

For patients with moderate-to-severe lymphedema (ISL stages II to III) and no contraindications, we suggest intensive physiotherapy, usually in the form of complete decongestive therapy, rather than less intense therapy. Complete decongestive therapy (CDT) refers to a two-phase (treatment phase, maintenance phase) multicomponent technique that is designed to reduce the degree of lymphedema and to maintain the health of the skin and supporting structures. (See 'Complete decongestive therapy' below.)

Patients with severe lymphedema (ISL stage III) may also benefit from intermittent pneumatic compression (IPC) in addition to CDT. IPC (also called sequential pneumatic compression) devices employ a plastic sleeve or stocking that is intermittently inflated over the affected limb. Most pneumatic compression pumps sequentially inflate a series of chambers in a distal-to-proximal direction. (See 'Intermittent pneumatic compression' below.)

Compression therapy — Compression therapy, often combined with physiotherapy in the form of manual lymphatic drainage (MLD), is used in the initial stages of lymphedema management. Limb compression uses multilayered padding materials and short-stretch (also called low-stretch) bandages. Maintenance therapy uses fitted compression garments (at least class I compression) worn during waking hours. A compression hand piece, either a glove or a gauntlet, is necessary when wearing a compression sleeve to prevent swelling in the hand. When correctly fitted and worn properly, compression garments can help reduce swelling; however, poorly fitted garments can be restrictive and can exacerbate lymphedema. (See "Clinical staging and conservative management of peripheral lymphedema", section on 'Compression therapy'.)

Compression garments and compression bandaging are effective for reducing limb lymphedema volume. Reported percentage reductions with compression garments or compression bandaging among various etiologies of lymphedema range from 17 to 60 percent [102]. In a randomized trial in 307 women who had undergone axillary lymph node dissection for breast cancer, those assigned to compression therapy developed arm swelling less frequently compared with the control group (14 versus 25 percent, as measured by relative arm volume increase) [57]. A separate trial randomly assigned 90 women with unilateral lymphedema to multilayered short-stretch bandaging for 18 days followed by elastic hosiery for 24 weeks with elastic hosiery alone for 24 weeks [103]. Combined therapy was approximately twice as effective in reducing limb volume (31 versus 16 percent at 24 weeks).

Manual lymphatic drainage — Manual lymphatic drainage (MLD) appears to offer an additional benefit to compression therapy for swelling reduction in patients with BCAL, particularly for those with mild-to-moderate lymphedema [104,105]. MLD is a massage-like technique that is performed by specially trained physical therapists [1]. MLD is also a component of complete decongestive therapy. (See 'Complete decongestive therapy' below.).

MLD and contraindications are described separately. (See "Clinical staging and conservative management of peripheral lymphedema", section on 'Manual lymphatic drainage' and "Clinical staging and conservative management of peripheral lymphedema", section on 'Contraindications'.)

Support for MLD in women with BCAL comes from both observational studies [106-109] and small randomized trials [63,104,110-112]. A systematic review that included six trials [104,110-112] concluded that MLD is safe and noted that MLD may offer additional benefit to compression bandaging for reducing swelling, more so for women with mild-to-moderate breast cancer-related lymphedema as compared with moderate-to-severe lymphedema [105]. In one of these trials with 31 women with BCAL, the reduction in excess volume and dermal thickness in the arm treated with MLD was greater compared with simple lymphatic drainage (SLD; a commonly taught self-help maneuver) [110]. MLD also significantly improved several quality-of-life domains, including emotional function, occurrence of dyspnea, and disturbances in sleep. It should be noted that not all studies have found a benefit for MLD. As an example, in one trial, 42 women with lymphedema were randomly assigned to standard therapy (compression garments, physical exercises, and education) with or without a short course of MLD (eight sessions in two weeks) [113]. After a follow-up of 12 months, both groups had a similar reduction in arm volume, suggesting that MLD had little impact over standard management.

Complete decongestive therapy — Complete decongestive therapy (CDT) is a multicomponent technique designed to reduce the severity of lymphedema and maintain the health of the skin and supporting structures [1]. For patients with moderate-to-severe lymphedema following treatment for breast cancer, CDT is recommended as a component of a multimodality regimen for the treatment of lymphedema [1]. (See "Clinical staging and conservative management of peripheral lymphedema", section on 'Complete decongestive therapy'.)

The effectiveness of CDT in women with breast cancer associated lymphoma is suggested in observational studies [114], which demonstrated a reduction in limb volume with improved pain, cosmesis, and/or function [106,115-126]. In these studies, reductions in limb volume range from 30 to 70 percent. However, patient compliance is required for long-term success. In one study, at least 90 percent of the lymphedema reduction was maintained in compliant patients at an average follow-up of nine months, while noncompliant patients lost approximately one third of the initial benefit [115]. Small randomized trials in patients with BCAL have mixed results [127-129].

In a small phase trial, 53 patients with BCAL were randomly assigned to CDT (lymph drainage, multilayer compression bandaging, elevation, remedial exercise, and skin care) or standard physiotherapy (bandages, elevation, head-neck and shoulder exercises, and skin care) [129]. The group receiving CDT had a significantly greater improvement in edema as measured by circumferential and volumetric measurements. A separate trial suggested minimal benefit for CDT over compression garments as a first-line treatment of lymphedema. In this trial, 95 patients with BCAL were randomly assigned to CDT or compression garments alone [128]. A greater absolute reduction in arm volume was seen for CDT compared with compression garments (250 versus 142 mL), but the mean reduction in arm volume was not significantly different (29 versus 23 percent). There were no differences in severe adverse events. Several factors may limit the applicability of the findings of these trials. The trial was small and may lack sufficient power to detect a significant volume difference. Also, the study excluded patients who had not responded to conservative strategies (eg, compression garments or bandaging). However, another small trial involving 52 patients with BCAL following mastectomy also found no significant difference in relative volume change for CDT compared with compression [127].

Intermittent pneumatic compression — Intermittent pneumatic compression (IPC; also called sequential pneumatic compression) is another method of compression therapy for patients with typically severe lymphedema. (See "Clinical staging and conservative management of peripheral lymphedema", section on 'Intermittent pneumatic compression'.)

A number of studies have evaluated the role of IPC in patients with lymphedema following breast cancer treatment [107,112,125,130-136]. A systematic review of IPC in patients with BCAL identified seven trials [137]. Among three trials that reported volume reductions [125,130,133], there were no significant differences between routine management of lymphedema with and without the use of IPC. On the other hand, IPC may still be an effective addition to a multimodality lymphedema treatment regimen. One of these trials randomly assigned 23 patients with unilateral previously untreated BCAL to CDT alone or with adjunctive IPC (30 minutes daily for 10 days) [125]. A significantly greater reduction in limb volume during initial treatment was seen for combined therapy compared with CDT alone (45 versus 26 percent). A second arm of the trial evaluated the efficacy of maintenance IPC therapy (self-administered 60 minutes daily) added to CDT in 27 patients with unilateral breast cancer-associated lymphedema who had previously been treated with CDT [125]. At 6 to 12 months, a fall in mean limb volume occurred with combined therapy compared with an increase with CDT alone (-90 versus +33 mL), a difference that was statistically significant.

In addition to the paucity of data demonstrating benefit from IPC in women with BCAL, there are a number of concerns:

The ideal pressure for the pump is not known, and some investigators suggest that a pressure greater than 60 mmHg may injure lymphatic vessels.

IPC is usually applied daily or five times per week. However, the optimal duration of IPC is not known, as in different studies, the sessions have varied in length (90 minutes to as long as 6 hours) and duration (two to three days to four weeks) [103,112,125,131,136].

Thus, IPC may be considered an adjunct in patients who do not respond well to CDT and compression garments. If the lymphedema is controlled with IPC, a gradient pressure garment should be worn to prevent further limb swelling. Clinical experience has shown that IPC may be an alternative maintenance program for lymphedema patients who have difficulty in performing self-MLD secondary to weakness, fatigue, or range of motion deficits. It may also be beneficial for lymphedema patients who are unable to utilize compression bandaging or garments due to skin allergies from the materials used in these compression products.

Surgery — For selected patients with lymphedema or complications related to lymphedema, surgery to help alleviate pain and discomfort and reduce the risk of infection, among other goals, may be reasonable to consider. Surgery is most effective for patients with early-stage lymphedema (ie, prior to tissue fibrosis and severe adipose deposition); however, surgery is also possible and effective in patients with late-stage lymphedema. Techniques include physiologic techniques to improve lymphatic circulation and tissue reduction techniques [138-140]. Techniques are discussed separately. (See "Surgical treatment of primary and secondary lymphedema".)

Palliative care — While compression and physiotherapy are beneficial for extremity lymphedema, their application may be associated with risk (eg, skin breakdown, fluid overload) when used in the context of metastatic cancer [141]. (See "Overview of comprehensive patient assessment in palliative care".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Lymphedema" and "Society guideline links: Breast surgery".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Peripheral lymphedema after cancer treatment (The Basics)")

Beyond the Basics topics (see "Patient education: Lymphedema after cancer surgery (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Lymphedema occurs when the load exceeds the transport capacity of the lymphatic system, which leads to the accumulation of protein-rich fluid (lymph) and fibroadipose tissue in the interstitium. Symptoms of lymphedema include limb swelling, skin changes, discomfort, and restricted range of motion. (See 'Introduction' above and 'Anatomy' above and "Clinical features and diagnosis of peripheral lymphedema", section on 'Clinical features'.)

Breast cancer and its associated therapies are one of the most common causes of secondary peripheral lymphedema. The incidence of upper extremity lymphedema in breast cancer survivors ranges from 5 to 40 percent depending upon the extent of lymph node disruption and other risk factors such as the presence of obesity or infection. Incidences in the higher range occur in patients who have undergone complete axillary dissection combined with radiation therapy. (See 'Incidence and risk factors' above.)

Breast cancer-associated lymphedema (BCAL) is primarily due to obstruction of the lymphatic channels located in the axilla, most commonly from lymphadenectomy or radiation therapy, but can also occur as a result of infiltration of the lymphatic vessels by tumor cells (lymphangitic carcinomatosis).

Primary prevention of lymphedema in patients undergoing treatment for breast cancer relies on surgical techniques that limit node dissection (eg, sentinel lymph node biopsy) or, less commonly, techniques that repair or bypass injured lymphatics, and limiting radiation exposure. Sentinel lymph node biopsy has been instrumental in decreasing the incidence of lymphedema, which occurs in <10 percent of patients who undergo sentinel node biopsy alone. (See 'Primary prevention' above.)

Monitoring and early identification of lymphedema and initiation of protection measures may help slow progression to a higher clinical stage. These measures are appropriate for all patients with lymphedema. (See 'Natural history and monitoring' above and 'Protection of the affected extremity' above.)

Patients should be encouraged to:

Monitor their extremity, including taking upper limb measurements. Report any changes.

Maintain skin and nails to prevent infection or skin injury.

Seek medical attention and treatment for any clinical signs of infection.

Elevate the extremity, when able.

Wear properly fitted graded compression sleeves.

Avoid medical procedures that puncture the skin.

Maintain ideal body weight.

Physical findings of asymmetric upper extremity measurements usually establish a diagnosis of lymphedema in at-risk patients. An onset of lymphedema several years after the primary surgery without obvious trauma should raise suspicion for tumor, in particular, recurrence of the breast cancer in the axillary area or the development of lymphangiosarcoma. (See 'Clinical features, diagnosis, and staging' above.)

For patients with upper extremity lymphedema, we measure blood pressure in the contralateral arm, particularly in any setting in which blood pressure is being closely monitored (eg, in an intensive care unit, recovery room, or during procedures). Among the rare patient who has undergone bilateral axillary lymph node dissection and has bilateral lymphedema, routine blood pressure measurements can be obtained in the lower extremity. (See 'Blood pressure measurement' above.)

The conservative treatment of established lymphedema consists of a multimodality regimen that includes general measures for care, physiotherapy (eg, simple lymphatic drainage, manual lymphatic drainage, complete decongestive therapy), and compression therapy (compression bandaging, compression garments, intermittent pneumatic compression), the type and the intensity of which depend upon the clinical stage. The effectiveness of these treatment in patients with BCAL is discussed above. (See 'Effectiveness of conservative treatments' above and "Clinical staging and conservative management of peripheral lymphedema", section on 'Conservative treatment by severity'.)

For patients with mild lymphedema (International Society of Lymphology [ISL] stage I), we suggest physiotherapy in the form of manual lymphatic drainage and compression garments, rather than more intensive therapy (Grade 2B). Manual lymphatic drainage (MLD) is a massage-like technique that is typically performed by specially trained physical therapists, but a self-help maneuver (simple lymphatic drainage) has also been used for mild cases. Light pressure is used to mobilize edema fluid from distal to proximal areas. (See 'Manual lymphatic drainage' above.)

For patients with moderate-to-severe lymphedema (ISL stages II to III) and no contraindications, we suggest intensive physiotherapy, usually in the form of complete decongestive therapy, rather than less intense therapy (Grade 2B). Complete decongestive therapy (CDT) refers to a two-phase (treatment phase, maintenance phase) multicomponent technique that is designed to reduce the degree of lymphedema and to maintain the health of the skin and supporting structures. (See 'Complete decongestive therapy' above.)

Patients with severe lymphedema (ISL stage III) may also benefit from intermittent pneumatic compression (IPC) in addition to CDT. IPC (also called sequential pneumatic compression) devices employ a plastic sleeve or stocking that is intermittently inflated over the affected limb. Most pneumatic compression pumps sequentially inflate a series of chambers in a distal-to-proximal direction. (See 'Intermittent pneumatic compression' above.)

For selected patients with lymphedema or complications related to lymphedema, surgery may be an option with the goals of alleviating pain and discomfort and reducing the risk of infection, among others. Surgery is most effective for patients with early-stage lymphedema (ie, prior to tissue fibrosis and severe adipose deposition); however, surgery is also possible and effective in patients with late-stage lymphedema. (See 'Surgery' above.)

Complications of lymphedema include skin infections (cellulitis, erysipelas, and lymphangitis), lymphangiosarcoma, and reduced quality of life, including aspects of emotional, functional, physical, and social well-being. (See "Clinical staging and conservative management of peripheral lymphedema", section on 'Complications'.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledge Emile R Mohler, III, MD, now deceased, who contributed to an earlier version of this topic review. UpToDate also acknowledges Dr. Mohler's work as our Section Editor for Vascular Medicine.

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Topic 104714 Version 32.0

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