Lymphedema is a feared complication of cancer treatment and one that negatively impacts survivorship. The incidence of breast cancer–related lymphedema ranges from 6% to 70%, but lymphedema may be a common and under-reported morbidity. No standard guidelines for its diagnosis and assessment exist. Although the true etiology of lymphedema remains unknown, radiation, chemotherapy, type of breast surgery, and extent of axillary surgery are commonly cited risk factors. However, the relationship between the number of nodes removed and the risk of lymphedema is not clearly correlated. Clinical trials are focusing on ways to reduce the need for axillary dissection even in the setting of a positive sentinel node, to help minimize axillary morbidity. Risk-reduction practices, including avoidance of skin puncture and blood pressures in the ipsilateral upper extremity, and precautionary behaviors such as wearing compression garments during air travel continue to be advocated by the medical and survivor communities, despite a lack of rigorous evidence supporting their benefit. Emerging data support exercise in at-risk and affected women with lymphedema when started gradually and increased cautiously.
As long as axillary surgery and/or radiation remain pillars of breast cancer treatment, lymphedema will remain a potential complication. Risk-reduction practices to further prevent lymphedema after axillary surgery have long been advised. It is here that many of the myths regarding lymphedema risk and prevention arise. The National Lymphedema Network, founded in 1988, seeks to educate and guide patients and healthcare providers about lymphedema and risk-reduction practices for those at risk for and affected by the disorder. The organization publishes guidelines on risk-reducing behaviors and seeks to answer the question of whether behavioral modifications can further limit or reduce lymphedema. The NLN’s risk-reduction guidelines were updated in 2011 and continue to carry a disclaimer stating that “there is little evidence-based literature regarding many of these practices, [therefore] the majority of the recommendations must at this time be based on the knowledge of pathophysiology and decades of clinical experience by experts in the field.” Although the National Comprehensive Cancer Network (NCCN) and the National Cancer Institute (NCI) do not publish specific guidelines regarding lymphedema diagnosis, treatment, or prevention, the NCCN and NCI websites for patients both describe and define lymphedema and endorse precautionary behaviors similar to those recommended by the NLN.[28,29] The primary goal of the risk-reducing measures is to prevent overload of the lymphatic system by limiting activities that may increase lymphatic flow, local blood flow, or metabolic waste products in the at-risk or affected limb. The recommended behaviors support activity, medical procedure, and lifestyle modifications. Although the lymphedema risk-reduction strategies promulgated by these national organizations are based on sound physiologic principles, the effect of each recommended measure on preventing lymphedema is unclear, as is the impact on one’s quality of life if these measures are followed. Although Boccardo et al documented that increased education and awareness can reduce the incidence of lymphedema, it is also possible that increased education can influence patient anxiety. One study reviewed factors affecting patients’ intention to avoid strenuous activity by following 175 women for a median of 10 months after axillary surgery. The authors found women given advice on arm care and those with perceived vulnerability regarding, and fear of, lymphedema were more likely to avoid using their arm (odds ratio [OR], 4.9; 95% CI, 1.73–14.06; P = .003; and OR 1.6, 95% CI 1.18–2.16, P = .003, respectively). Interestingly, however, the extent of axillary surgery did not influence the women’s arm use (OR, 1.3; 95% CI, 0.56–3.11; P = .52).
Several additional inconsistencies exist regarding risk-reduction behaviors. First, standardized advice does not meet the needs of all patients, especially given that the recommendations do not always differentiate between at-risk and affected individuals. Second, there is inconsistent application of the practices across disease sites. While these recommendations are frequently discussed in relation to breast cancer treatment, they are rarely discussed within the context of other malignancies that require lymph node assessment or treatment. Further, many additional patients annually undergo lymph node excision for diagnosis of lymphoma or infection. Ironically, they leave the hospital without having discussed future lymphedema risk with their physicians, despite having a number of lymph nodes removed that is comparable to that of a patient undergoing SLNB for breast cancer. Third, there is still debate over what constitutes a risk-reducing practice. Patients recognize these controversies, given that they frequently receive inadequate or conflicting advice regarding arm care.
Despite these inconsistencies, breast cancer survivors have adopted many of the existing lymphedema risk–reducing practices. A prospective study of nearly 1000 breast cancer survivors found that patients having ALND practice a mean of 5.1 risk-reducing behaviors, while those having SLNB follow 4.3. Although this difference was statistically significant (P < .0001), one could argue that it is not clinically significant. For example, more than 98% of women who have undergone ALND avoid blood pressures, intravenous catheter placement, and needle sticks in the ipsilateral arm, while more than 80% of SLNB patients do the same without documented benefit and theoretically less risk than those having ALND. Examination of the recommended risk-reducing behaviors reveals few objective data for or against each measure. The data regarding commonly considered precautionary behaviors are summarized in Table 1. An in-depth review of the role of compression garments when flying, and of IV placement, needle sticks, blood pressures, and exercise, follows.
The physiologic theory supporting the role of compression garments during air travel stems from the low cabin pressure that exists during flight, which causes a decrease in extracellular fluid pressure. This pressure decrease facilitates escape of fluid and proteins from the lymphatic vasculature, resulting in lymphedema. A literature review finds only a single retrospective survey–based study of patients with lymphedema published more than 15 years ago, in which 27 of 490 (5.5%) patients surveyed link the onset or worsening of their lymphedema to an airplane flight. The authors of this study cited lowered cabin pressure as the cause but do note the lack of direct evidence. Based on this report and its suggested physiologic premise, at-risk and affected patients are recommended to wear a compression garment, to help regulate the extracellular pressure and support the lymphatic musculature maintaining lymphatic flow. Limited contemporary data, however, do not appear to support these findings or the use of compression garments. Graham et al retrospectively surveyed 287 at-risk survivors regarding air travel. Overall, 50% of them traveled a mean of five flights, and of this group 86% practiced precautionary behaviors consisting of routine use of compression garments with or without other behaviors. The authors observed no difference in lymphedema rates between fliers and nonfliers (P = .42), but interestingly they found the practice of precautionary behaviors to be associated with an increased risk of lymphedema (OR, 6.2; 95% CI, 1.2–20.8; P < .04) among those flying. Furthermore, when analyzed independently, the use of compression garments appeared not to correlate with other suspected lymphedema risk factors, including nodal disease, number of nodes removed, or radiation. They concluded that garments were not necessary and might be counterproductive. Kilbreath et al drew similar conclusions after they prospectively evaluated 72 women preflight and 6 weeks after planned international or transcontinental air travel. Bioimpedance analysis in one study found no difference in extracellular fluid content between baseline and follow-up, regardless of flight distance or compression garment use. Despite their short follow-up and the fact that the women followed were athletes (which may have a protective effect), the authors concluded that air travel did not cause lymphedema.
Another long-supported myth regarding prevention of lymphedema is the avoidance of IV catheters or needle sticks. The theory behind this practice arises from the possible risk of infection produced by accidental and nonaccidental skin punctures and is less concerned with the actual puncture itself. Infection will cause an intense inflammatory response, altering the extremity fluid homeostasis. Despite the longevity of this landmark recommendation, a review of the literature finds only one article supporting the practice. Clark et al prospectively followed 188 women for lymphedema and measured them at baseline, 6 months, and 3 years after axillary surgery. At 3 years, patients were also questioned about skin punctures. Overall, 39 (21%) had lymphedema at 3 years. Among other risk factors, univariate analysis found skin puncture for IV catheter insertion, venipuncture for blood draw, or finger stick for blood glucose testing were associated with a significant increased risk for lymphedema, with a risk ratio of 2.44 (95% CI, 1.33–4.47). These data should be interpreted cautiously; 18 of 188 (9.5%) reported remembering any type of skin puncture, and of these 18 women only 8 had lymphedema at the 3-year follow-up. Patients with lymphedema may be more likely to recall previous skin puncture than those without symptoms.
Hand surgery ipsilateral to the side of prior axillary surgery could be considered a severe form of skin puncture, lending relevance to the IV and venipuncture question. A small number of studies in the hand surgery literature address this occurrence. Dawson et al reported on 15 women undergoing carpel tunnel release ipsilateral to the side of prior axillary dissection; none had a post–hand surgery infection, new onset of lymphedema, or worsening of existing lymphedema symptoms. In a second series, Hershko and Stahl retrospectively reviewed all hand surgeries performed between 1983 and 2002 and identified only 25 women with 1-year follow-up, of whom 4 had lymphedema at the time of hand surgery and 21 did not. Lymphedema was determined by patient perception only and noted to be worse after surgery in 2 women, each of whom had pre-existing lymphedema. The authors noted no progression or new symptoms in the remaining 23 women. Interestingly, they did not use preoperative antibiotics on any patient, performed 24 of 25 surgeries under local anesthesia, and used a tourniquet in all cases. Gharbaoui et al surveyed the members of the American Society for Surgery of the Hand. Among the 606 surgeons returning the surveys, more than 95% said they have willingly performed hand surgery on patients with a history of ipsilateral lymphadenectomy, radiation, or both. Surgeon willingness to operate decreases if lymphedema is present but remains quite high at 85%. Overall, 94% and 74% of surgeons routinely use tourniquets in women without and with lymphedema, respectively. Surgeon recollection identified fewer complications of infection, lymphedema, or delayed wound healing among patients without lymphedema (3% vs 23%). These three studies offer marginal data and anecdotal reports at best about the safety of ipsilateral skin puncture as they are all retrospective with small numbers, are fraught with recall bias, and lack any objective measurements. Despite this, each study calls for re-evaluation of the skin puncture guidelines as they relate to lymphedema risk. Perhaps the authors should also conclude that re-evaluation of the ipsilateral blood pressure guidelines is warranted, as their data demonstrated a clear willingness to use tourniquets with minimal reported morbidity. No documented studies to date have reviewed the recommendation to avoid ipsilateral blood pressure measurements. Clearly, these conclusions must be interpreted with caution, and further study is warranted. While the recommendations to wear compression garments while flying, and to avoid IV sticks, venipuncture, and blood pressures are made with good intention and based on sound physiologic principles, few rigorous data support them. Unfortunately, though, without good scientific data supporting or refuting these practices, both clinicians and patients are still faced with the clinical dilemma of whether or not they should encourage or disregard these behaviors.
Finally, exercise has historically been discouraged for breast cancer survivors, based on the belief that it would increase metabolic waste and extracellular fluid accumulation in the extremity, causing lymphedema. Over the last 5 years, the recommendation to avoid exercise has been challenged. Aside from recommended flexibility and remedial exercises used to reduce arm swelling and promote mobility during lymphedema treatment, exercise consists of resistance exercises (weight lifting), aerobic exercise, or a combination of both. Robust data support the value of resistance exercise in both at-risk and affected women. In fact, five of six randomized controlled trials (RCTs) published between 2006 and 2010 found weight lifting to be associated with minimal risk of developing or exacerbating lymphedema. The largest study with the longest follow-up is the physical activity and lymphedema trial (PAL) that followed 141 women with breast cancer–related lymphedema. Patients were randomized to either weight training while wearing a compression sleeve, which was supervised twice weekly, or to a control group who were asked not to alter their exercise level. At 1-year follow-up, the authors found no increase in lymphedema in the intervention group and, further, found fewer and less severe lymphedema exacerbations in the weight training group. The follow-up study evaluating weight training in at-risk survivors also found no difference in lymphedema rates between the two groups but interestingly found that among women with more than five nodes removed, those in the weight training group were significantly less likely to develop lymphedema than those in the control group (7% vs 22%, P = .003).
Based on these data, the NLN now supports the safety of resistance exercises in a controlled manner, starting with small weights, low repetition, and gradual progression. In general, compression garments should be worn during exercise in women with lymphedema and considered on an individual basis for women at risk for lymphedema.
A recent meta-analysis reviewed seven studies evaluating aerobic exercise in people with lymphedema. Among the three randomized controlled trials and the four literature reviews, aerobic exercise or the combination of resistance and aerobic exercise did not trigger lymphedema or increase its incidence. Despite the relative agreement between the studies, the meta-analysis cautions that the benefits of aerobic exercise should be weighed against potential harms, as the data were not robust. Specifically, only one of three RCTs had more than 50 patients, but it was hampered by a trial adherence rate of only 70%. Although aerobic exercises appear safe, additional well-designed studies with larger numbers and longer follow-up are needed.
As long as evaluation and treatment of the axilla are necessary, lymphedema will continue to be a potential morbidity. It is hoped that the move towards personalized medicine, by individualizing surgery, radiation, and chemotherapy regimens, will help to reduce the incidence of treatment morbidities, including lymphedema. Until the risk of lymphedema is eliminated, however, risk-reduction practices will remain a consideration for all breast cancer survivors. Clinicians should recognize that patients are not at equal risk for lymphedema and that data do not support a standardized approach nor allow for complete disregard of risk-reduction behaviors. Exercise in a monitored fashion is likely to be safe in all survivors, and the recommendation not to exercise appears to be the only myth surrounding lymphedema that has been scientifically disproven.
Financial Disclosure: The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
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