Abstract

Tumor invasion into draining lymph nodes, especially sentinel lymph nodes (SLNs), is a key determinant of prognosis and treatment in breast cancer as part of the TNM staging system. Using multicolor histology and quantitative image analysis, we quantified immune cells within SLNs from a discovery cohort of 76 breast cancer patients. We found statistically more in situ CD3+ T cells in tumor negative vs. tumor positive nodes (mean of 8878 vs. 6704, respectively, p = 0.006), but no statistical difference in CD20+ B cells or CD1a+ dendritic cells. In univariate analysis, a reduced hazard was seen with a unit increase in log CD3 with HR 0.49 (95% CI 0.30–0.80) and log CD20 with HR 0.37 (95% CI 0.22–0.62). In multivariate analysis, log CD20 remained significant with HR 0.42 (95% CI 0.25–0.69). When restricted to SLN tumor negative patients, increased log CD20 was still associated with improved DFS (HR = 0.26, 95% CI 0.08–0.90). The CD20 results were validated in a separate cohort of 21 patients (n = 11 good outcome, n = 10 poor outcome) with SLN negative triple-negative breast cancer (TNBC) (“good” mean of 7011 vs. “poor” mean of 4656, p = 0.002). Our study demonstrates that analysis of immune cells within SLNs, regardless of tumor invasion status, may provide additional prognostic information, and highlights B cells within SLNs as important in preventing future recurrence.

Highlights

  • Lymph node metastasis is a frequent early event in many cancers, forming one of three major factors in the TNM staging system

  • We compared the numbers of CD3+ T cells, CD20+ B cells, and CD1a+ dendritic cells per mm[2] area in tumor-invaded nodes to tumor-free lymph nodes (Fig. 2)

  • Prediction of disease-free survival In Table 2, we summarize the univariate and multivariate Cox regression results evaluating DFS based on sentinel lymph node (SLN) immune cells, tumor invasion, stage, grade, ER/PR+ vs. ER/PR−, age at diagnosis, and tumor size

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Summary

Introduction

Lymph node metastasis is a frequent early event in many cancers, forming one of three major factors in the TNM staging system. Lymph node invasion is a key determinant of risk and treatment. Our previous studies have shown that T cells and dendritic cells in axillary tumor-draining lymph nodes (TDLNs) may be altered in some breast cancer patients and can predict clinical outcome.[7,8,9] B cells are another major immune cell population, but their role in cancer is less well studied. B cells isolated from TDLNs, SLNs, can recognize cancer-associated antigens and are capable of producing antibodies against those antigens.[12,13] In this study, we assessed the association of T cells, B cells, and dendritic cells within SLN with or without tumor invasion with disease-free survival (DFS) in breast cancer patients

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