Prognostic significance of immunologic factors and metabolic parameters in triple-negative breast cancer

Abstract

Purpose: Triple negative breast cancers (TNBCs) are particularly aggressive tumors, however emerging data clearly indicate that TNBC is a heterogeneous class with variable prognosis according to clinical, pathologic, and genetic factors. We investigated the prognostic impacts of metabolic and immunologic signatures in TNBC. Materials and Methods: Between February 2004 and December 2011, 145 patients with TNBC who had undergone preoperative 18F-FDG PET/CT were included. The metabolic standardized uptake value (SUVmax), metabolic tumor volume (MTV) as well as the total lesion glycolysis (TLG) of primary tumor were measured, and the expression of programmed death ligand-1 (PD-L1), programmed cell death 1 (PD-1), and Ki-67 proteins were evaluated in 117 tumor samples. The prognostic impact and relevance among parameters were assessed. Results: At a median follow up of 53 months after surgery, 5-year progression-free survival (PFS) was 76% and 5-year overall survival (OS) was 82%. With a cut-off value of 6.06, high SUVmax group had significantly worse PFS (5-year: 88% vs. 74%, p = 0.021). High MTV (≥ 2.54) and high TLG group (≥ 5.57) also showed significantly worse PFS. High SUVmax group had younger patients (< 50), more advanced T stage (≥ T3), higher N stage (N3), and higher grade (grade 3) than low SUVmax group. Strong positive staining of PD-L1 (> 70%) was noted in 37 patients (32%). PD-L1 expression was significantly correlated with larger tumor size and PD-L1 strong positive group showed significantly poor prognosis (5-year PFS 59%, 5-year OS 70%), especially high rate of systemic recurrence. High PD-L1 expression and N3 stage were significant in multivariate analysis for both PFS and OS. Conclusion: Increased 18F-FDG uptake on PET/CT and PD-L1 expression was associated with significantly inferior clinical outcome, and it was correlated with several unfavorable prognostic factors including larger tumor size.