What is the issue?
Many women in the world are affected by breast cancer. Radiotherapy and surgery used for breast cancer treatments target the breast, chest and axilla (or armpit) of the affected side and could damage the local lymphatics of those regions. This results in poor drainage of fluid from the affected arm, which could lead to a sensation of heaviness and visible swelling. A term used to describe this condition is lymphoedema. Lymphoedema is well-recognised by patients and health care professionals. It is uncomfortable and could interfere with many aspects of daily life. In addition, some patients regard their one-sided arm swelling as unsightly. Long-term swelling could also degrade the quality of the skin and lead to recurrent skin infections. Traditional measures to manage this troublesome condition include arm exercises, massage, and compression stockings. While these measures are effective in reducing the arm swelling, they require time, patience, and daily dedication on the patient's part, and can come at a cost to the patient. These traditional measures need to be continued lifelong in order to remain effective.
Study question
Health care professionals have examined alternative ways to manage lymphoedema after breast cancer treatment. This report reviews the effectiveness of surgical techniques that have been developed to either prevent or treat this condition.
Study results
A number of techniques have been proposed, but only three studies published by November 2017 met the inclusion criteria for our present review. Two studies looked at preventing lymphoedema and one study looked at treating lymphoedema. In total, these three studies involved 131 individuals.
Two studies focused on the surgical technique of lymphaticovenular anastomosis (a preventive procedure), which joins lymphatic vessels to blood vessels and utilises the circulatory system to drain the excess fluid from the arm. They showed that individuals who undergo this surgical procedure have a reduced risk of developing lymphoedema (255 fewer cases of developing lymphoedema per 1000 women, where the true value may be somewhere between 118 fewer to 300 fewer cases developing lymphoedema per 1000 women) compared to those who do not. These two studies did not provide data for important secondary outcomes such as patient-reported outcomes, ability to discontinue further interventions for lymphoedema, surgical complications, or long-term complications.
One study evaluated a vascularised lymph node transfer technique which transferred a piece of tissue containing lymph nodes from the groin or abdomen to the armpit of the limb affected by lymphoedema. The authors observed that those who underwent this procedure experienced reductions in:
- limb volume: on average, women who underwent the procedure had 39% reduction in limb volume compared to those who had standard care alone;
- pain: on average, women who had the procedure scored 4.16 points lower on a 10-point scale (i.e. 1 = no pain, 10 = extreme pain) than those who had standard care alone;
- heaviness sensation: on average, women who had the procedure scored 4.27 points lower on a 10-point sensation heaviness scale (i.e. 1 = no heaviness sensation, 10 = extreme heaviness sensation) compared to those who had standard care alone; and
- infection: on average, women who had the procedure had 1.22 fewer infections per year compared to those who had standard care alone.
The vascularised lymph node transfer technique also provided a gain in functional improvement meaning that, on average, women who underwent the procedure scored 3.77 points better on the overall function score (function measured on a 10 point scale where 1 = excellent function, 10 = very poor function) compared to those who had standard care alone. The study did not provide data for some important secondary outcomes such as the ability to discontinue further interventions for lymphoedema or long-term complications.
Certainty of the evidence
The certainty of the evidence supporting the use of lymphaticovenular anastomosis in the prevention of lymphoedema was low, consisting of only two small studies from one centre. Similarly, only one single-centre study assessed the use of vascularised lymph node transfer and provided overall very low-certainty evidence supporting the use of the procedure in the treatment of upper limb lymphoedema.
There is low-certainty evidence that lymphaticovenular anastomosis is effective in preventing the development of lymphoedema after breast cancer treatment based on the findings from two studies. One study providing very low-certainty evidence found that vascularised lymph node transfer is an efficacious option in the treatment of established stage 2 lymphoedema related to breast cancer. Important secondary outcomes in this review were rarely reported in the included studies. More high-quality RCTs are required to further elucidate the effectiveness of surgical interventions in the prevention and treatment of lymphoedema after breast cancer treatment. At the time of this review, no ongoing trials on this topic were identified.
Breast cancer is the most common type of cancer amongst women worldwide, and one distressing complication of breast cancer treatment is breast and upper-limb lymphoedema. There is uncertainty regarding the effectiveness of surgical interventions in both the prevention and management of lymphoedema affecting the arm after breast cancer treatment.
1. To assess and compare the efficacy of surgical interventions for the prevention of the development of lymphoedema (LE) in the arm after breast cancer treatment.
2. To assess and compare the efficacy of surgical interventions for the treatment of established LE in the arm after breast cancer treatment.
We searched the Cochrane Breast Cancer Group’s Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the WHO International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for all prospectively registered and ongoing trials on 2 November 2017. Reference lists of included studies were also handsearched by three review authors for additional eligible trials.
All randomised controlled trials (RCTs) comparing a surgical intervention for the prevention or treatment of lymphoedema of the arm after breast cancer treatment to either standard intervention, placebo intervention, or another surgical intervention were included. Patients of both sexes and all ages who have had treatment for their breast cancer were considered. No limits were applied to language or study location. Three authors independently determined the eligibility of each study.
Three authors independently extracted data for each included study using a pre-designed data extraction pro forma and used Cochrane's 'risk of bias' tool for assessing risk of bias. Dichotomous variables were analysed using the Mantel-Haenszel method to estimate risk ratios (RRs). Differences in continuous variables were expressed as mean differences (MDs). GRADE was used to assess the certainty of the evidence provided by the included studies.
Two studies involving 95 participants examined surgical interventions for preventing breast cancer-related lymphoedema. Both studies evaluated the efficacy of the lymphaticovenular anastomosis technique as part of a preventative management protocol. Both studies were deemed to be at unclear risk of bias overall. Statistical variation between the studies was low, which increases the reliability of the evidence. However, the two studies were conducted in the same centre. Lymphaticovenular anastomosis appears to result in a reduction in the incidence of lymphoedema compared to nonoperative management with a risk ratio of 0.20 (95% CI 0.06 to 0.63, P = 0.006; 95 participants; low-certainty evidence). The RCTs did not evaluate any of the secondary outcomes.
One study involving 36 participants evaluated the effectiveness of vascularised lymph node transfer for treating breast cancer-related lymphoedema. The trial was deemed to be at unclear risk of bias. For participants suffering from stage 2 lymphoedema, the evidence suggested reductions in limb volume (MD -39.00%, 95% CI -47.37% to -30.63%, very low-certainty evidence), pain scores (MD -4.16, 95% CI -5.17 to -3.15, very low-certainty evidence), heaviness sensation (MD -4.27, 95% CI -5.74 to -2.80, very low-certainty evidence), mean number of infections/year (MD -1.22, 95% CI -2.00 to -0.44, very low-certainty evidence), and an improvement in overall function scores (MD -3.77, 95% CI -4.89 to -2.65, very low-certainty evidence) for those who had undergone vascularised lymph node transfer compared to those who had undergone no treatment.