Unnecessary lymphadenectomy following breast cancer surgery could become a thing of the past
Researchers unmask how changes in a ‘hidden’ network in human lymph nodes affect breast cancer survival
New research funded by Breast Cancer Now (London, UK) has uncovered changes in the structure of lymph nodes that could one day help identify people who are at higher or lower risk of breast cancer spreading. This could guide treatment decisions and help more people avoid unnecessary treatment.
Lymph nodes are small organs that play a key role in the immune system, helping the body fight infections and cancer. In breast cancer, the lymph nodes in the armpit are often the first place the disease spreads to.
Determining whether breast cancer has reached the lymph nodes is an important part of planning treatment. Right now, everyone with invasive breast cancer undergoes surgery to remove one or more lymph nodes to check for cancer cells. While this is effective, it can lead to long-term side effects like swelling of the arm (lymphoedema) and may be unnecessary for some.
But we still don’t fully understand how and when lymph nodes change in a way that allows breast cancer to spread and how these changes impact treatment effectiveness and survival.
Dr Amy Llewellyn and Dr Kalnisha Naidoo from King’s College London, in collaboration with Professor Sophie Acton at University College London (all UK), studied 331 lymph node samples taken from people with different types of breast cancer and compared them to healthy lymph nodes from people without cancer.
They looked at a unique group of cells within lymph nodes called fibroblastic reticular cells (FRC). The FRC network within lymph nodes provides the structure for the lymph node, controls fluid flow and activates different immune cells.
The researchers found that the structure of this FRC network can change even before the breast cancer has spread. This means that tumours affect the lymph nodes before any cancer cells can be seen there.
These structural changes were different depending on the type of breast cancer, how far the cancer had spread, and whether someone had received chemotherapy. Some changes were associated with a better chance of survival, while others were linked to poorer outcomes.
Now, the researchers are planning to study what molecules are responsible for these lymph node changes to untangle these complex interactions between breast cancer and the immune system.
In the future, this insight could be used to better identify people at higher or lower risk of the disease progressing. This could pave the way for more personalised treatment decisions and ensure more people avoid unnecessary side effects.
Understanding how these structural changes impact lymph node function could also open up new ways to treat the disease.
Dr Amy Llewellyn from King’s College London said: “Until now, we have not fully understood how and when lymph nodes become altered in a way that allows cancer to spread.
“As a result, every breast cancer patient currently must have some of their lymph nodes removed for accurate staging and treatment planning. While this is effective, it can lead to long-term complications and may be unnecessary for some patients, particularly those with early-stage disease or those whose cancer responds well to treatment.
“There is therefore an urgent need to better understand the biology of the lymph node chain and our study addresses this gap by providing the first large-scale analysis of FRC in human lymph node tissue from breast cancer patients.”
Dr Simon Vincent, chief scientific officer at Breast Cancer Now, which funded the research, said: “These findings suggest that changes to the structure of the lymph nodes are more than just a consequence of the cancer. They can also play an active role in helping breast cancer progress.
“With one person tragically dying from breast cancer every 45 minutes in the UK, we urgently need research like this so that we can better understand who is most at risk of their cancer progressing and becoming incurable. Only then can we find ways to stop it.
“With a better understanding of how lymph nodes change as breast cancer spreads, we could find new targets for future treatments for types of breast cancer that are harder to treat.”
Ruth Smith, 59, from Buckinghamshire, was diagnosed with triple-negative breast cancer in January 2023 after discovering a lump in her right breast.
Ruth said: “When I met with my oncologist for the first time, I remember him saying that I was extremely lucky – had we been having the conversation a few months earlier, the prognosis would have been very different, as NICE had very recently licensed a drug called paclitaxel to be used in combination with immunotherapy and chemotherapy to treat my type of cancer with encouraging success rates.
“After months of gruelling treatment, in July 2023 I had a PET scan which showed no sign of cancer. But I still had surgery at the end of August, in which they removed some of the breast tissue to check and they also removed all my lymph nodes. I rang a helpline and the amazing nurse explained that this was because lymph nodes can be like a string of pearls, and the cancer can move through these, so they have to remove them all.
“Going through breast cancer treatment and being told that lymph nodes needed to be removed was daunting, and at the time I just focused on doing whatever was necessary to treat the cancer. Living with lymphoedema afterwards has been a constant reminder of what I went through – it developed on my arm like a series of 10p pieces in April 2024. The swelling and discomfort can have a real impact on daily life, and it’s something I now have to manage long term. I was fortunate to participate in a trial for a new type of surgery. This hasn’t completely improved things but has stopped it from getting worse.
“Research like this is so important because it could help doctors better understand who really needs which treatments, and hopefully reduce the number of people who go on to develop lymphoedema in the future.”
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