The Immune Response in Nonmetastatic Axillary Lymph Nodes Is Associated with the Presence of Axillary Metastasis and Breast Cancer Patient Outcome

Abstract

Tumor cells can modify the immune response in primary tumors and in the axillary lymph nodes with metastasis (ALN⁺) in breast cancer (BC), influencing patient outcome. We investigated whether patterns of immune cells in the primary tumor and in the axillary lymph nodes without metastasis (ALN^-) differed between patients diagnosed without ALN⁺ (diagnosed-ALN^-) and with ALN⁺ (diagnosed-ALN⁺) and the implications for clinical outcome. Eleven immune markers were studied using immunohistochemistry, tissue microarray, and digital image analysis in 141 BC patient samples (75 diagnosed-ALN⁺ and 66 diagnosed-ALN^-). Two logistic regression models were derived to identify the clinical, pathologic, and immunologic variables associated with the presence of ALN⁺ at diagnosis. There are immune patterns in the ALN^- associated with the presence of ALN⁺ at diagnosis. The regression models revealed a small subgroup of diagnosed-ALN⁺ with ALN^- immune patterns that were more similar to those of the ALN^- of the diagnosed-ALN^-. This small subgroup also showed similar clinical behavior to that of the diagnosed-ALN^-. Another small subgroup of diagnosed-ALN^- with ALN^- immune patterns was found whose members were more similar to those of the ALN^- of the diagnosed-ALN⁺. This small subgroup had similar clinical behavior to the diagnosed-ALN⁺. These data suggest that the immune response present in ALN^- at diagnosis could influence the clinical outcome of BC patients.