Breast-cancer-related lymphoedema is a substantial problem in women after they have undergone breast cancer treatment. Despite the introduction of breast-conserving surgery and minimal lymphatic intervention (eg, sentinel-lymph-node biopsy [SLNB]), incidence rates remain disappointingly high. In The Lancet Oncology, Tracey DiSipio and colleagues1 report the findings of their systematic review and meta-analysis in which they shown that roughly one in five women with breast cancer will develop arm lymphoedema.1 The incidence was four times higher in women undergoing axillary lymph-node dissection compared with those who received sentinel-lymph-node biopsy.
Lymphoedema is the accumulation of lymph in the interstitial spaces caused by the failure of the lymph-conducting system (lymph and lymph glands) to absorb or transport lymph back to the blood circulation.2 The drainage basin of the axillary lymph glands is the ipsilateral breast, upper quadrant of the trunk, and the upper limb. Consequently, any disruption to lymph flow through the axilla can result in lymphoedema in any part of the drainage basin. With breast conservation rather than mastectomy as standard treatment, breast lymphoedema has become much more of a clinical problem but has received much less research attention. Because breast lymphoedema can occur without arm swelling, the overall incidence of breast cancer-related lymphoedema within the forequarter is probably higher than data for arm swelling alone suggest.
The pathophysiology of breast cancer-related lymphoedema is complicated. Although interference with lymph drainage routes is fundamental to its development, the exact mechanisms leading to swelling are poorly understood. In view of the consistency of treatment protocols for breast cancer, some clinical questions remain unanswered. Why do most women not develop breast cancer-related lymphoedema? Why can such lymphoedema develop either immediately or many years after having breast cancer? Why is the distribution of swelling in the arm non-uniform (eg, a patients’ forearm can be swollen but not their hand)? If lymphatic obstruction post-surgery is the cause, then the whole upper limb could be expected to be affected, but this is often not the case.
Findings from studies done since 2009 have shown that after axillary surgery and before the onset of oedema, women who later develop breast cancer-related lymphoedema have higher lymph flows (and not lower as one might expect) than women who do not develop lyphoedema.3 Lymph flow is also increased in the contralateral arm, indicating axillary surgery has a systemic not just a regional effect.3, 4 Furthermore, lymphatic pump failure develops in established breast cancer-related lymphoedema.5 One hypothesis is that an as-yet-unidentified subgroup of women with higher lymph flows develop such lymphoedema because of the chronically increased lymph load working against increased lymphatic outflow resistance, which then causes lymphatic pump failure.6
DiSipio and colleagues identified obesity and more extensive surgery as risk factors lent support by strong evidence. Whereas more extensive surgery as a prognostic factor is understandable, the relation between obesity and arm lymphoedema is more complex. A functional link has emerged between lymphatic malfunction and the pathogenesis of obesity.7Furthermore, much of the swelling that occurs with arm lymphoedema is fat not fluid, which has led to liposuction as a treatment for breast cancer-related lymphoedema when first-line decongestive lymphatic therapy (manual lymph drainage, compression and exercises) has fully resolved the fluid component.8
The lymphatic system is the most common route for cancer spread and, in theory, blocking that route would do much to reduce cancer mortality. The problem has been that for centuries the lymphatic system has been the subject of gross neglect, mainly because of the absence of investigations to realise its importance to human pathology and disease. But that shortfall is changing, with the discovery of new lymphatic genes and molecular proteins.7 However, until a new drug that can modulate lymph flow or lymphatic function is developed, the lymphatic system, and in particular lymphoedema, will remain under-recognised by most practising oncologists. Attempts at improving lymph drainage by surgical means has had a resurgence with the development of lymphaticovenular anastomoses9 and lymph-node transfer operations.10 Lymph-node transfer combined with VEGF-C to stimulate lymphangiogenesis is entering phase 1 trials.7 Ideally, such developments will generate greater awareness and interest in lymphoedema, which remains one of the most common and distressing consequences of breast cancer and its treatment.