Researchers unmask how changes in a ‘hidden’ network in lymph nodes affect breast cancer survival

Dr Amy Llewellyn and Dr Kalnisha Naidoo from King’s College London, in collaboration with Professor Sophie Acton at University College London, have been studying a network of cells in the lymph nodes.

Their research has revealed that changes to the structure of this network could one day be used to better identify people at higher or lower risk of breast cancer progressing. 

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 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 complications such as lymphoedema, and may be unnecessary for some people.

But until now, we haven’t been able to understand how and when lymph nodes change in a way that allows breast cancer to spread and what this could mean for predicting treatment success.

Amy and her team analysed 331 lymph node samples taken from 179 people with different types of breast cancer and compared them to healthy lymph nodes.

In this study, the researchers focussed on a unique network of cells found within lymph nodes called fibroblastic reticular cells. This network can act like scaffolding to provide structural support. And it can also help control the movement and activity of immune cells.

They used special stains that highlighted different features of cells within the lymph nodes to map the network of fibroblastic reticular cells.

And with a clearer view of the structure of this network, they were able to compare this to clinical data. This included details about their tumours, the treatments they’d received and how they responded over time.

This analysis revealed many hidden secrets. First, they found that the structure of this network can start to change before breast cancer has spread. This suggests that tumours may be able to affect lymph nodes before cancer cells can be seen there.

In people whose cancer had not spread to the lymph nodes, certain subtypes of the disease such as triple negative breast cancer had a denser, more connected network. And the researchers found that this was linked to improved survival.

But in cases where breast cancer cells had already spread to the lymph nodes, similar changes to the network were linked to worse survival.

The team also saw how as cancer grows in the lymph nodes, the network becomes more damaged and disrupted. And this was also linked to poorer outcomes.

And finally, the researchers found that after chemotherapy, this network of fibroblastic reticular cells can be replaced by scar-like tissue, showing how treatment reshapes the lymph node environment.

So, the researchers believe that the structure of this network is strongly related to breast cancer progression and how people respond to treatment over time.

Taken together, the findings suggest that the structure of the lymph nodes is more than just a consequence of the cancer. Instead, it can play an active role in breast cancer progression and response to treatment.

Now, the researchers are planning to study what molecules are responsible for these lymph node changes. And in doing so, they hope to untangle the complex interactions between breast cancer and the immune system.

In the future, this could be used to better identify people at higher or lower risk of disease progression. Paving the way for more personalised treatment decisions and ensuring more people can avoid unnecessary side effects.

And understanding how these structural changes impact lymph node function could also open up new ways to treat the disease.

This research was made possible through funding from Art for Cure and the Dame Vera Lynn Breast Cancer Now Clinical Research Training Fellowship. The project was also supported by funding from Cancer Research UK.