Secondary lymphoedema

Secondary lymphoedema — Lymphoedema of the arm following treatment for breast cancer

1.Background

Breast cancer-related lymphoedema (BCRL) is a common side effect of the treatment for breast cancer. It is classified as a secondary lymphoedema, meaning it is secondary to a definable cause, namely the damage by surgery and radiotherapy to the lymph drainage paths (lymph nodes and vessels) in the axilla, or armpit region. The arm, including or excluding the hand, swells and may become painful, heavy, and difficult to use; the swelling may lead to psychological difficulties, e.g. associated with altered body image. Sometimes part of the trunk swells also. Occasionally, arm swelling is severe and disfiguring but in many cases it is mild and may even be unrecognised by the individual (see images, below). There are other forms of secondary lymphoedema, for instance of the legs following pelvic surgery.

BCRL usually begins within 2-3 years of completion of breast cancer treatment. Swelling is usually permanent and when untreated tends to worsen with time, but with treatment (compression hosiery, exercise, massage, and skin care) the swelling can be contained, controlled and reduced. The number of women in the UK with BCRL is not known precisely but it is believed to affect approximately 25% of women who have been treated for breast cancer. The introduction of sentinel lymph node biopsy for breast cancer may reduce the number of cases. Curiously, some women undergoing complete surgical clearance of the axilla do not go on to develop BCRL whereas some still develop swelling after the removal of only one lymph node. The reason for this may be that some women are more susceptible to BCRL than others, and that genetic factors account for this. Overall, an incidence of BCRL of 6-11% has been reported following sentinel node biopsy.

2.Recent research findings

Using an imaging technique called fluorescence video-microscopy we have found evidence for the growth of new blood vessels and new lymphatic vessels in the skin of the swollen arm (haemangiogenesis and lymphangiogenesis). These phenomena have functional consequences for the physiological turnover of fluid in the arm tissues. Haemangiogenesis may fuel the swelling to some extent, whereas lymphangiogenesis may indicate that lymph (tissue fluid that has entered lymphatic vessels) is re-routed into and along the skin. Both occur only after swelling has developed.

The fluid drainage function of the lymphatic system can be measured in the skin and deeper tissues by quantitative lymphoscintigraphy. Lymph drainage from the subcutis (just under the skin) is reduced where swelling occurs (e.g. in the forearm), but not in the absence of swelling (in the spared hand of the otherwise swollen arm, or in the arm of women treated for breast cancer but without BCRL). Drainage from the muscle is reduced in proportion to the severity of the swelling, even though the muscle itself is not enlarged — in BCRL the swelling principally involves the skin and subcutis. This finding is significant and lymph drainage in the muscle is probably pivotal to the mechanisms underlying the swelling.

An uneven distribution of swelling along the length of the arm is commonly seen. Regions of mild and marked swelling within the same forearm have been examined using lymphoscintigraphy. Surprisingly, whereas no differences in drainage were found between these sites in swollen arms, a systematic difference in lymph drainage was identified along the axis of the arm, whether swollen or not. Unexpected findings frequently crop up and confound the investigation of (initially) straightforward hypotheses aimed at unravelling the pathophysiological puzzle of BCRL.

Employing the imaging capability of the gamma camera in lymphoscintigraphy, our recent development of a novel technique to measure human lymphatic pump function in vivo enabled us to measure the pumping capability of the larger lymphatic collector vessels in the arm in health and in BCRL. The lymphatic collectors running up the arm (and present elsewhere in the body) possess muscular walls and squeeze or pump their contents along, against gravity if need be. We found that the ‘pump pressure’ (the pressure that the lymphatic vessels could overcome) is 38% lower in swollen arms than in arms of healthy volunteers. We believe that in some breast cancer patients, the function of the lymphatic collectors in the arm begins to fail following axillary surgery, the vessels being faced with increased resistance to the drainage of lymph through the axilla. Swelling develops when lymph drainage by the weakened vessels can no longer match the unceasing filtration of fluid into the tissues by the capillaries. An analogy would be the eventual development of cardiac failure in individuals with chronically raised blood pressure (i.e. raised afterload). This new technique will prove useful in assessing future treatments for BCRL.

3.Future Work

We are currently completing a 5-year programme of research, funded by the Wellcome Trust.