Breast cancer (BC) is mostly detected at an early stage but can be diagnosed with de novo (dn) metastases. Oligometastatic BC (OMBC) is distinguished from polymetastatic BC (PMBC) based on a limited disease burden usually defined by a cut-off of 5 metastases and is associated with a better prognosis. The immune system could be implicated in the control of the OMBC state by limiting metastatic dissemination. Here we compared tumour immune infiltrates in a cohort of dn OMBC and dn PMBC and correlated them with survival.
Clinicopathological characteristics at diagnosis of 115 dn OMBC and 117 dn PMBC patients were retrospectively collected. Tumour-infiltrating lymphocytes (TILs) were quantified on standard H&E staining. Immune infiltrates of 31 dn OMBC and 42 dn PMBC primary tumours were further characterized using multiplex multispectral immunochemistry (mIHC) allowing detection of CD4, CD8, FoxP3 T and CD20 B cells classified as intra-tumoral (i) or stromal (s) according to their localization. Epithelial cells were marked with pancytokeratin. Survival analyses were assessed using Cox’s proportional hazards models.
In both cohorts, BC were mostly staged cT2 with lymph node involvement. Patients with dn OMBC had lower neutrophil/lymphocyte ratios, LDH and CA15-3 levels and showed a better outcome. No statistical differences were noted regarding TIL levels (median 5% in OMBC, 0% in PMBC) or their immune spatial distribution and most tumours were classified as “cold”. mIHC revealed that CD4 and CD8 T cells were the most represented TILs. Very few FoxP3 T and CD20 B cells were present. We noted a significantly higher infiltration of iCD4, iCD8 and iFoxP3 T cells in dn OMBC. Similar findings were found for sCD4 T cells (p<0.001). Median CD4/CD8 ratios in both compartments were significantly higher in dn OMBC (p=0.001). Of interest, each 10% increment of sCD8 T cells were associated with better OS (HR: 0.48, p=0.034) and PFS (HR: 0.57, p=0.047) only in dn OMBC. sCD4/CD8 and sCD8/FoxP3 ratios were also correlated with survival in dn OMBC. In both cohorts iCD20 B cells were associated with worse survival.
Here we show that CD8 T cells have prognostic value in dn OMBC but not in dn PMBC suggesting a potential role of immunotherapy in this setting, and it should be further investigated.
Institute Jules Bordet.
Association Jules Bordet.
All authors have declared no conflicts of interest.