Histiocyte Quantity in Tumor-Negative Sentinel Lymph Nodes Predicts 10-Year Disease-Free Survival in Patients With Breast Cancer.

BACKGROUND AND AIM: The sentinel lymph node (SLN) play a key role in the host antitumor immune response. Microarchitectural patterns in tumor-negative SLNs (SLNneg) may provide important clinical information about the host's antitumor immune response against breast cancer.

METHODS

This retrospective cohort study included SLNneg from 339 breast cancer patients. SLNneg microarchitectural features (percentage (%) SLNneg area occupied by histiocytes, germinal centers, lymphocytes outside germinal centers, adipocytes, vessels or connective tissue) were quantified morphometrically. The relationship with 10-year disease-free survival (DFS) was investigated using Cox regression analyses. Variables showing a nonlinear relationship with survival, cubic spline analysis was used to identify distinct groups.

RESULTS

SLNnegs were predominantly occupied by lymphocytes (median % SLNneg area: 60%) followed by histiocytes (14%), vessels (7%), connective tissue (5%), adipocytes (5%) and germinal centers (0.4%). Histiocyte quantity was related to survival in a nonlinear fashion with 9% and 21% as relevant cutoffs. Patients with < 9% or > 21% SLNneg area occupied by histiocytes had poorer survival compared to patients with 9% to 21% SLNneg area occupied by histiocytes (< 9% SLNneg area Hazard Ratio (HR) 2.5 (95% CI, 1.4-4.5), P = .001; > 21% SLNneg area HR 2.7 (1.5;4.7), P < .001; 9% to 21% SLNneg area = ref.), remaining significant in multivariable analysis. The other microarchitectural features were not related to survival.

CONCLUSION

This is the first study showing that quantity of histiocytes in SLNneg is associated with 10-year DFS in breast cancer in a nonlinear manner. This suggests that cell type specific morphological changes within the SLNneg reflect the host's antitumor immune response providing clinically relevant information in breast cancer patients.