A study to understand more about breast cancer related lymphoedema

Cancer type:

Breast cancer

Status:

Results

Phase:

Other

This study looked at why some women develop a swelling of the arm called lymphoedema, a few months or years after surgery for breast cancer.

Most cases of lymphoedema happen within 3 years of the surgery. Researchers were trying to understand how the drainage of tissue fluid from the arm goes wrong in lymphoedema. And why some women get it but most do not.

Cancer Research UK supported this study.

More about this trial

Tissue fluid is produced constantly and comes from the very small blood vessels (capillaries) throughout the body. At the same time as it is formed, the fluid is drained away by the lymphatic system.

When the tissue fluid cannot drain away quickly enough it builds up and the tissue swells. This is lymphoedema.

Researchers know that the root cause of arm lymphoedema following breast cancer is removing lymph glands in the armpit area (axilla) with surgery. But they don’t understand why some women develop lymphoedema and others do not.

Researchers think that some women may be naturally more likely to develop lymphoedema, whatever surgery they had. The aim of this study was to look into this and the possible reasons for it.

Summary of results

The researchers found some differences in women who developed breast cancer related lymphoedema.

They found that women who are most likely to develop lymphoedema have a higher rate of lymph flow in their arms. This means that their lymphatic system works hard to pump fluid around. Any problems with lymphatic drainage, such as having their lymph glands removed, or an increase in lymph fluid in these women is more likely to cause their lymphatic system to fail and lymphoedema to develop.

Everyone taking part was in 1 of 4 study groups.

Study 1 measured the rate of lymph drainage in the muscle in both arms.
Study 2 measured the rate at which tissue fluid forms in the arms
Study 3 looked at the pumping function of the tubes that carry lymph (lymphatic vessels)

The people in these groups took part before their surgery. This is so the researchers could investigate whether these things were any different in the women who later developed lymphoedema.

Study 4 looked at the possible connections between the tubes (vessels) that carry lymph fluid and blood vessels. Researchers believe that having these connections may protect against lymphoedema in some women, or help it to be less severe.

study diagram

Study 1
38 women took part in study 1. 

They had their arms measured using a machine called a perometer. This measures the size of the arms using light beams. After the perometer reading, they had an injection of a tiny amount of radioactive tracer [Gloss/Radioactive injection] into the muscle in both arms.

They then had gamma camera [Gloss/Gamma camera] photos taken of each arm and armpit. This recorded the amount of radioactivity left in each arm over 3 hours, and the lymph drainage was worked out from this.

The study team then saw:

  • 38 women before surgery
  • 33 women at around 8 weeks after surgery

The women returned to the hospital laboratory to have their arms checked. 7 of the 38 women later developed lymphoedema.

The team found that the women who had a higher lymph flow rate before surgery were more likely to develop lymphoedema. They think that the lymphatic vessels may be overloaded and so more likely to fail after surgery.

At the moment, doctors generally think that removing the lymph nodes in the armpit affects the lymph drainage in the arm, so causing a build-up of fluid. The researchers of this study think this is not necessarily the case. They think the lymph fluid may find other nodes to drain away from.

Study 2
13 women took part in study 2. 

Everyone had a perometer reading. Then they had a blood pressure cuff inflated on each arm in turn and the pressure in the cuff was decreased in small steps until no pressure remained. This test lasted around half an hour per arm.

The researchers did this to measure the amount of fluid filtering from the blood circulation into the tissues by measuring the increase in the size of the arm during the time the blood pressure cuff was inflated.

This was done before surgery and then around 19 weeks after surgery. The women were followed by the study team for 3 years.

7 of the 13 women developed lymphoedema.

The team found no link between the amount of fluid filtering (or leaking) into the tissues and the development of lymphoedema. 

The type of breast cancer treatment people had did not seem to have a significant impact on the amount of tissue fluid measured. 

There were difficulties with this study and the researchers think the technique they used needs improvement.  They believe that, if people have an impaired lymphatic system, increased fluid filtration could mean that fluid gradually gathers in the tissues and this could lead to lymphoedema. 

Study 3
26 women took part in study 3. 

Everyone had a perometer reading, they then had a blood pressure cuff inflated on the arm on the same side as their cancer. They had a radioactive tracer injection into the skin, and gamma camera pictures taken of this arm. The pressure in the cuff was gradually reduced.

From this the doctors could measure the pressure at which the lymph fluid was pumped by the lymphatic vessels.

This was done before surgery and then repeated at around 21 weeks after surgery. The women were followed by the study team for 3 years to check their arms.

10 of the 26 women developed breast cancer related lymphoedema.

The women who had a higher pumping pressure were more likely to develop lymphoedema. Breast cancer treatment did not seem to have a significant impact on the pressures but it did impair the way the lymph fluid is transported up the arm.

The researchers think that a couple of factors could affect someone whose lymphatic system is already working at a high rate:

  • interference with lymph drainage from the arm caused by surgery to the lymph nodes in the armpit (axilla)
  • an increase in the amount of lymph fluid

These could tip the lymphatic system into chronic failure which would result in lymphoedema.  

They think that if these women could be identified as having a higher risk before surgery, it might be possible to give treatment to reduce the amount of lymph fluid. Such as treatment with drugs. This could potentially prevent lymphoedema.

Study 4
15 women took part in the study 4. There were 2 groups of women.

In the first group, 5 women were seen before surgery and had a perometer reading. Then a blood sample was taken and some of their own red blood cells were tagged with a radioactive tracer (radiolabelled) and then given to them as an injection into the arm.

Pictures were taken so the researchers could track the movement of the red blood cells. They also had blood tests.

This was repeated 2 to 6 weeks after surgery.

This helped the researchers to see if there were any connections between the tubes (vessels) that carry lymph fluid, and blood vessels (these connections are called lymphovenous communications or LVCs).

The study team saw the women again between 1 to 2 years after surgery. At these visits their arms were checked for lymphoedema. None of the women developed breast cancer related lymphoedema by the time of their final follow-up visit.

In the second group, 10 women who had had surgery at least 3 years previously had the same tests as above. Of these 10 women, 7 had lymphoedema. These women only had the tests once.

The study team found that in some women in both groups the levels of the tagged red blood cells indicated movement (shunting) from the lymph vessels to the blood vessels in the arm. This was more marked in the women who did not have lymphoedema.

It is probable that the women with these LVCs always had these connections and it is part of how their bodies work.

The findings were complex and the researchers say that a larger study is needed to see if people with LVCs are protected against lymphoedema.

Overall, the researchers think there is a small group of women who are more likely to develop breast cancer related lymphoedema. This might be triggered by genetic factors. The researchers’ findings raise the possibility that this group of women could be identified before surgery. And also the possibility of developing drug treatments to prevent or lessen lymphoedema.

We have based this summary on information from the research team. The information they sent us has been reviewed by independent specialists (peer reviewed) and published in a medical journal. The figures we quote above were provided by the trial team who did the research. We have not analysed the data ourselves.

Recruitment start:

Recruitment end:

How to join a clinical trial

Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Professor PS Mortimer

Supported by

Cancer Research UK
Experimental Cancer Medicine Centre (ECMC)
National Institute for Health Research Cancer Research Network (NCRN)
St George's Healthcare NHS Trust

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

Oracle 7958

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Harriet wanted to try new treatments

Picture of Harriet

“I was keen to go on a clinical trial. I wanted to try new cancer treatments and hopefully help future generations.”

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