King's College London

Axillary lymph nodes (ALNs) are central to how breast cancer spreads and how patients are treated, but they also play an important role in the body’s immune response. While treatment has shifted towards less invasive approaches, there is still limited understanding of how the lymph node environment influences cancer progression.

Within these lymph nodes, a specialised network of fibroblastic reticular cells (FRCs) provides essential structural support and regulates immune cell movement and activity. However, how this network changes during cancer progression has remained unclear.

In a new study published in the Journal of Pathology, researchers analysed the architecture of the FRC network in lymph node samples from breast cancer patients to determine whether structural changes could be linked to disease outcomes.

The team identified platelet-derived growth factor receptor beta (PDGFRβ) as a reliable marker for visualising FRCs, enabling consistent mapping of the network across disease states. Using this approach, they analysed 331 lymph node samples from 179 breast cancer patients, alongside healthy control tissue.

Structural features of the network were then assessed in relation to detailed clinical data, including tumour characteristics, treatment history, and survival outcomes.

The researchers found that structural changes in the lymph node environment occur even in nodes that appear free of cancer, suggesting that tumours may influence distant immune structures before visible spread occurs. In more aggressive subtypes such as triple-negative breast cancer (TNBC), the FRC network became significantly denser and more complex. Interestingly, this denser and more interconnected FRC network was associated with improved survival only when chemotherapy was given to TNBC patients before surgery.

In contrast, in patients with lymph node involvement, similar structural changes were linked to poorer outcomes.

In addition, in lymph nodes with metastatic disease from all breast cancer subtypes, greater disruption of the network was linked to higher tumour burden and worse survival, while more organised and aligned networks were associated with better outcomes.

This suggests that lymph node remodelling may have beneficial or harmful effects depending on disease context and treatment timing.

She added: "As a pathologist, I also just love that good old-fashioned immunohistochemistry when paired with newer computational analysis has provided novel (and cool) insights into this complex disease!"

The research findings demonstrate that changes in the structure of FRC networks in axillary lymph nodes can help predict breast cancer outcomes. These findings could improve how patients are assessed and stratified by risk in future.

"With further validation, this approach could form the basis of new biomarkers to help risk stratify patients and potentially spare some people from unnecessary surgery or side effects."

The researchers also emphasise that further validation in larger cohorts is needed before the approach can be translated into routine clinical use but highlight its potential to transform understanding of how the immune microenvironment influences cancer progression.

This research was supported by funding from Breast Cancer Now and Cancer Research UK.