Background: EBV has been linked with a number of human malignancies, including African Burkitt’s lymphoma, classical Hodgkin’s disease, posttransplant and acquired immune deficiency syndrome-associated lymphoproliferative disorders, sinonasal NK/T cell lymphoma, nasopharyngeal carcinoma and gastric carcinoma. In recent years, it hasbeen questioned whether EBV may play a role in the development of breast carcinoma (BC), which is the most common malignant tumour and the leading cause of cancer in women in Western countries.

Patients. 127 individuals (100% women aged between 28 and 61) were included in this study. Most of the patients with BC (64,6%) were postmenopausal. The diagnosis of BC and the histopronostic Scarff-Bloom and Richardson classification (SBR) were made by use of criteria described by Contesso et al. (1987). The majority of the tumors (90%) were of the ductal type. The histopathologic grade of invasive carcinomaaccording to the SBR classification was as follows: 15,5% for type I, 51,8% for type II, 24,5 for type III and 8,2% the SBR was unknown. In this study, 55,5% of the patients were node negative.

Methods: We studied the incidence of EBV infection in 76 cases of BC by using a real-time quantitative PCR assay for EBV DNA (detection threshold : 5 copies/µg of tumor) in order to analyze the viral burden both in peripheral blood mononuclear cells (PBMC) and in tumour cells from BC patients. In parallel, Immunophenotyping (including TCR Vb repertoire) and functional studies (T lymphocyte and NK frequencies based on cytokine response) were performed.

Results: Copies of EBV genomes were detected and amplified in 22 (32,4%) cases and no association was observed between EBV detection by PCR in biopsy and tumor histology. In addition, no association was observed between the presence of EBV in tumors and prognostic factors such as tumor size, menopausal status, steroid hormones receptors, Cerb2 and Ki67 expression, SBR grade. Nevertheless, the proportion of EBV-positive tumors was significantly higher in carcinomas from female aged between 30-49 years thanfrom female aged between 50-69 years (p = 0.003). In a second time, we tempt to evaluate the impact of EBV status on the evolution of disease with time. 81 among the 100 documented patients had a favorable evolution (five years after primary surgery) and did not experience relapse or complications. In contrast, 19 patients suffered of relapse or died. EBV was more frequently detected in tumors from the patients who have favorable evolution (36% versus 18%); moreover EBV loads higher than 100 copies/µg were found more frequently in patients with positive evolution, than in patients with poor evolution (p = 0.02). Interestingly, these patients harbouring high viral loads in tumors exhibited memory T cells displaying particular TCR Vb expansions.

Conclusion: Overall, our results strength the idea of an association between BC and EBV. The correlation between favorable evolution and high EBV loads in tumors associated with persistent TCR expansions, may indicate that EBV could lead to a better immune surveillance in these patients. Finally, this well-known oncogenic and persisting virus could be considered as a positive “image” as inducer of a better immunosurveillance in BC patients. The determination of the EBV status in BC patients as prognosis marker is discussed.

Gina Marrao is a PhD student (cotutelle thesis at Grenoble1 (F) and Coimbra (P)