A high neutrophil-lymphocyte ratio and platelet-lymphocyte ratio are associated with a worse outcome in inflammatory breast cancer.

INTRODUCTION: Inflammatory breast cancer (IBC) is an uncommon, but aggressive form of breast cancer that accounts for a disproportionally high fraction of breast cancer related mortality. The aim of this study was to explore the peripheral immune response and the prognostic value of blood-based biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), in a large IBC cohort. PATIENTS & METHODS: We retrospectively identified 127 IBC patients and collected lab results from in-hospital medical records. The differential count of leukocytes was determined at the moment of diagnosis, before any therapeutic intervention. A cohort of early stage (n = 108), locally advanced (n = 74) and metastatic breast cancer patients (n = 41) served as a control population. RESULTS: The NLR was significantly higher in IBC compared to an early stage breast cancer cohort, but no difference between IBC patients and locally advanced breast cancer patients was noted. In the metastatic setting, there was also no significant difference between IBC and nIBC. However, a high NLR (>4.0) remained a significant predictor of worse outcome in IBC patients (HR: 0.49; 95% CI: 0.24-1.00; P = .05) and a lower platelet-lymphocyte ratio (PLR) (≤210) correlated with a better disease-free survival (DFS) (HR: 0.51; 95% CI: 0.28-0.93; P = .03). CONCLUSION: Patients with a high NLR (>4.0) have a worse overall prognosis in IBC, while the PLR correlated with relapse free survival (RFS). Since NLR and PLR were not specifically associated with IBC disease, they can be seen as markers of more extensive disease.

Infiltrating stromal immune cells in inflammatory breast cancer are associated with an improved outcome and increased PD-L1 expression.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare and rapidly progressive form of invasive breast cancer. The aim of this study was to explore the clinical evolution, stromal tumour-infiltrating lymphocytes (sTIL) infiltration and programmed death-ligand 1 (PD-L1) expression in a large IBC cohort. PATIENTS AND METHODS: Data were collected prospectively from patients with IBC as part of an international collaborative effort since 1996. In total, 143 patients with IBC starting treatment between June 1996 and December 2016 were included. Clinicopathological variables were collected, and sTIL were scored by two pathologists on standard H&E stained sections. PD-L1 expression was assessed using a validated PD-L1 (SP142) assay. A validation cohort of 64 patients with IBC was used to test our findings. RESULTS: Survival outcomes of IBC remained poor with a 5-year overall survival (OS) of 45.6%. OS was significantly better in patients with primary non-metastatic disease who received taxane-containing (neo)adjuvant therapy (P = 0.01), had a hormone receptor-positive tumour (P = 0.001) and had lower cN stage at diagnosis (P = 0.001). PD-L1 positivity on immune cells (42.9%) was higher in IBC than in non-IBC in both our patient samples and the validation cohort. Furthermore, PD-L1 expression predicted pCR (P = 0.002) and correlated with sTIL infiltration (P < 0.001). sTIL infiltration of more than 10% of the stroma was a significant predictor of improved OS (HR 0.47, 95% CI 0.27-0.81, P = 0.006) in a multivariate model. CONCLUSIONS: IBC is characterised by poor survival and high PD-L1 immunoreactivity on sTIL. This suggests a role for PD1/PD-L1 inhibitors in the treatment of IBC. Furthermore, we showed that PD-L1 expression predicts response to neo-adjuvant therapy and that sTIL have prognostic significance in IBC.

Current and future role of circulating tumor cells in patients with epithelial ovarian cancer.

Circulating tumor cells (CTCs) are viable tumor cells that are released into the circulatory system. CTCs have shown a prognostic value in numerous solid tumors. CTC research in epithelial ovarian carcinoma (EOC) has attracted only little attention. Since the primary route of metastasis in EOC is considered to be direct peritoneal spread in the abdominal cavity and distant metastases only occur in one third of the patients, it was thought that there is not enough shedding of tumor cells in the circulation. Nevertheless recent studies revealed an important role of hematogenous spread in EOC and showed that CTC status is associated with advanced tumor stage, CA-125 levels and residual disease after surgery. Furthermore the presence of CTCs correlates with shorter overall and disease free survival. However this prognostic value of CTCs in EOC seems to depend on the used isolation and detection methods. In EOC function- or density based enrichment methods seem to offer more promising results then epithelial cell adhesion molecule (EpCAM)-based approaches. This can be explained by a low number of EpCAM positive CTCs in EOC and the downregulation of EpCAM during epithelial-to-mesenchymal transition (EMT). The presence of CTCs might also have predictive value as CTC status was associated with treatment response in two studies and CTCs showed to be a better monitoring tool then CA-125 in a small population. The (genotypic) characterization of CTCs might become even more important in the future paving the way for CTCs to a true predictive "liquid tumor biopsy".