Another issue has also been addressed in a previous publication comparing EBV DNA levels in peripheral blood with the viral load in the tumor specimens. detected EBV genomes in approximately 50% of BC specimens, revealing viral loads which greatly varied from tumor to tumor. In their study combining laser capture microdissection techniques with real-time quantitative PCR, Arbach et al. Following this report, other authors detected EBER-2 and LMP-2 DNA by polymerase chain reaction (PCR) in 51% of breast cancers, compared to only 10% in normal tissue from the same patients, thus demonstrating that the EBV could be restricted to tumor epithelial cells. A link between the EBV and BC was first proposed when two studies detected EBV DNA in whole tumor material in 50% of their studied cases. Yet the results remain unconvincing, and their interpretation has been a matter of debate for several years. Since 1995, various studies have reported detecting the EBV in BC cases. For nearly two decades now, reports have suggested that the Epstein–Barr virus (EBV) may constitute a putative factor in BC natural history. The replicative form of EBV, as investigated using anti-ZEBRA titers, correlated with poorer outcomes, whereas the latent form of the virus that was measured and quantified using the EBV tumor DNA conferred a survival advantage to BC patients, which could occur through the activation of non-specific anti-tumoral immune responses.īreast cancer (BC), the most common cancer in women, is considered a heterogeneous disease with pathological characteristics such as morphology, grade, and hormone-receptor profile used in order to stratify tumors into biologically- and clinically-distinct groups. Those who recovered from their disease were found to have a measurable EBV DNA load, together with a high frequency of IFN-γ and TNF-α producing PBMCs (p = 0.04), which indicates the existence of a Th1-type polarized immune response in both the tumor and its surrounding tissue. Notably, patients exhibiting anti-ZEBRA antibodies at high titers experienced poorer overall survival (p = 0.002). No correlation was found between: (i) EBV detection in tumor or PBMCs and tumor characteristics (ii) EBV and other prognostic factors. Our study represents the first ever report of the impact of EBV on the clinical outcome of BC patients, regardless of tumor histology or treatment regimen. The effect of the EBV load in the blood or tumor tissue on patient survival was analyzed using univariate and multivariate analyses, combined with an analysis of covariance.
Immunological studies were performed on a series of 35 patients randomly selected from the second half of the survey, involving IFN-γ and TNF-α intracellular immunostaining tests performed via flow cytometry analysis in peripheral NK and T cells, in parallel with EBV signature. We also examined the EBV replicating form by the titration of serum anti-ZEBRA antibodies. We assessed 85 BC patients over an 87-month follow-up period to determine whether EBV infection, evaluated by qPCR in both peripheral blood mononuclear cells (PBMCs) and tumor biopsies, interacted with host cell components that modulate the evolution parameters of BC.
We have now presented prospective data on the effect of EBV infection combined with survival in patients enrolled in a prospective study. Yet the results are unconvincing, and their interpretation has remained a matter of debate.
For nearly two decades now, various studies have reported detecting the Epstein-Barr virus (EBV) in breast cancer (BC) cases.