Introduction
The incidence of lymph-edema in breast cancer patients can rise to 40% [1, 4]. The symptoms consist of a tired or heavy feeling, pain, tingling, limitations in movement, limitations in daily functioning, skin abnormalities and increased risk of infections. Lymph-edema arises when balance between supply and drainage of lymphatic fluid is disturbed [6]. It has a major impact on people's daily lives, having both physical and psychological consequences.
A commonly and widely used staging system of the International Society of Lymphology (ISL) distinguishes in the development of lymph-edema three stages (stages 1-3) [2]:
Stage 1: Presence of edema reduced by treatment or arm elevation (pitting edema); Stage 2: Edema partially reduced by treatment (pitting and non-pitting edema), intractable and progressive; Stage 3: Elephantiasis with skin lesions and relapsing infections.
Diagnosis
The complaints and physical examination together with measuring the swelling are the most important starting point for diagnosis. Different methods have been described on how to measure swelling, all with their pros and cons [4]. A 2 cm increase in circumference, measured at 10 cm from the olecranon, is commonly used to define lymph-edema, but there is no international consensus on the exact point from when one speaks of 'clinically relevant' lymph-edema and on the point from when one should start treatment, since it also depends on the possible presence of other signs of lymph-edema. The Dutch guideline proposes to define lymph-0edema when the volume is increased with 5-10%, corresponding to grade 1 toxicity on the CTC-AE 5.0 scale.
Preventing lymph-edema
Risk factors for developing lymph-edema, consist of patient-related and treatment-related risk factors. The most important factors that can be influenced by the patient herself consist of obtaining a healthy BMI (< 25 kg/ m2), adequate skin care and sufficient physical exercise, since this is important to stimulate the pump function of the muscles. Other non-modifiable patient-related factors are genetic factors: recent and ongoing studies in treatment-induced lymph-edema have suggested (epi) genetic predispositions yielding an increased risk of developing lymph-edema [4].
Treatment-related risk factors are the extent of axillary surgery, radiotherapy and chemotherapy. For chemotherapy, especially especially taxane-based regimens, have been associated with both transient and persistent lymph-edema [4]. Axillary surgery and/or radiotherapy are being de-escalated to reduce the risk on lymph-edema, whilst maintaining oncological control. Apart from completely omitting axillary surgery or radiotherapy, a more selective development is identification of those axillary lymph nodes that take care of drainage of the arm, by axillary reverse mapping (ARM). Recent studies indicate that when these nodes are spared from surgery [8] or radiotherapy [3, 7], the risk on lymph-edema is reduced [7]. Further prospective studies have to be carried out whether omitting surgery or radiotherapy to that region is oncological safe, and whether it indeed reduces the risk on lymph-edema.
Treatment of lymph-edema
The conservative treatment consists of a starting and a maintenance phase. In the starting phase reduction of the edema is the most important goal; during the maintenance phase the main goal is prevention of an increase in volume. The conservative treatments consist of compression therapy, physical exercise, reducing risk factors like a high BMI, adequate skin-care, and treatment of pain and psychosocial problems. The effectiveness of manual lymph drainage is disputed by several systematic reviews with a meta-analysis concluding that it has no or very little additive effect on compression therapy [4]. During the maintenance phase usually, elastic compression sleeves are used, in combination with self-management tools. Combining pneumatic compression with manual lymph drainage has been suggested but not sufficiently evaluated.
When conservative measures do not have sufficient effect, microsurgical approaches constructing an anastomosis, have been shown to be effective in reducing excess lymphatic fluid in early-stage lymph-edema [5]. Other more experimental surgical strategies that are being explored to deal with severe lymph-edema, consist of vascularized lymph node transfer and liposuction.
References
1. Armer JM & Stewart BR. Lymphology. 2010; 43:118–27.
2. 2016 Consensus document of the International Society of Lymphology. Lymphology. 2016;49:170–84.
3. Gross JP, et al. Int J Radiat Oncol Biol Phys 2019; 105: 649– 58.
4. McLaughlin SA et al. Ann Surg Oncol. 2017, doi: 10.1245/s10434-017-5982-4.
5. McLaughlin SA et al. Ann Surg Oncol. 2017 doi: 10.1245/s10434-017-5964-6.
6. Rockson SG. Curr Treat Options Cardiovasc Med. 2012;14:184–92
7. Waldstein C, et al. J Med Imaging Radiat Oncol 2021.doi: 10.1111/1754-9485.13318.
8. Yue T, et al. Clin Breast Cancer. 2015;15:301–6.