Non-Metastatic Axillary Lymph Nodes Have Distinct Morphology and Immunophenotype in Obese Breast Cancer patients at Risk for Metastasis.

Obese patients have worse breast cancer outcomes than normal weight women including a 50% to 80% increased rate of axillary nodal metastasis. Recent studies have shown a potential link between increased lymph node adipose tissue and breast cancer nodal metastasis. Further investigation into potential mechanisms underlying this link may reveal potential prognostic utility of fat-enlarged lymph nodes in breast cancer patients. In this study, a deep learning framework was developed to identify morphological differences of non-metastatic axillary nodes between node-positive and node-negative obese breast cancer patients. Pathology review of the model-selected patches found an increase in the average size of adipocytes (p-value=0.004), an increased amount of white space between lymphocytes (p-value<0.0001), and an increased amount of red blood cells (p-value<0.001) in non-metastatic lymph nodes of node-positive breast cancer patients. Our downstream immunohistology (IHC) analysis showed a decrease of CD3 expression and increase of leptin expression in fat-replaced axillary lymph nodes in obese node-positive patients. In summary, our findings suggest a novel direction to further investigate the crosstalk between lymph node adiposity, lymphatic dysfunction, and breast cancer nodal metastases.