Nodal status in luminal A invasive breast cancer: relationships with cytotoxic CD8 + and regulatory FOXP3 + cells tumor-associated infiltrate and other prognostic factors

Abstract

Luminal A breast cancers are generally associated with low metastatic potential and good prognosis. However, there is a proportion of patients, who present with metastases in lymph nodes. The aim of our study was to determine the association between the number of positive lymph nodes and infiltrates of tumor-associated cytotoxic CD8 + (CTLs), regulatory FOXP3 + T cells (Tregs), as well as other prognostic factors. Immunohistochemistry (IHC) for CD8 + and FOXP3 + was performed in 87 formalin-fixed paraffin-embedded primary breast cancer tissues, and cell infiltrate was assessed under light microscope. We observed that node-positive cases were associated with higher numbers of Treg cells and lower CTL/Treg ratio. There was also an inverse correlation between the CTL/Treg ratio and the number of metastatic lymph nodes. Similar relationships were found between the number of metastatic lymph nodes and Treg density or CTL/Treg ratio in pT1 BC. An elevated intratumoral CTL/Treg ratio was associated with pN0 stage. The relationship between lymphovascular invasion (LVI) and Treg density was also noted in node-negative tumors. In addition, more advanced nodal stage was related to LVI, higher pT, and lower PR expression. The numbers of CD8 + and FOXP3 + were also associated with tumor size, histologic grade, PR expression, and mitotic index. The results of our study suggested that the levels of tumor-infiltrating regulatory and cytotoxic cells as well as the balance between them play a role in lymphovascular spread of luminal A breast cancers.

Alteration of the immune microenvironment in the axillary metastatic lymph nodes of luminal A breast cancer patients

“…In this study, we observed a higher frequency of intratumoral CD4 + T cells and a lower frequency of intratumoral CD8 + T cells in primary BC at stage N1 than in BC without metastasis. In contrast to our results, node-positive luminal A BCs were reported to be associated with increased numbers of Treg cells and a decreased CD8+/Treg ratio [ 14 ]. Furthermore, a high frequency of Foxp3 + regulatory T cells (Tregs) relative to CD8 + T cells might be related to reduced progression-free survival and overall survival in breast cancer patients [ 15 ].…”