Since the few data exploring a possible association between Epstein–Barr virus (EBV) and breast cancer are conflicting, we investigated this association together with the influences of geographical areas. 509 breast cancers were sampled from areas with varying risks of nasopharynx carcinoma (NPC) such as North Africa (Algeria and Tunisia, high-risk area); southern France (Marseille, intermediate-risk area); and northern Europe (northern France, the Netherlands and Denmark; low-risk areas). Polymerase chain reaction (PCR) of a subregion of EBV BamHIC encoding the EBERs demonstrated that 31.8% of the tumours contained the viral genome. No significant differences were observed among the geographical areas. However, positive samples showed higher loads of the EBV genome in the NPC high- and intermediate-risk areas than in the low-risk areas. EBV type 1 was the dominant strain. In situ hybridization studies using a 35 S-labelled riboprobe for EBER1 and a laser capture microdissection, combined with quantitative PCR, showed that EBV localization was restricted to some tumour epithelial cell clusters. EBV could not be detected in the stroma. Considering the whole population covered, the presence of the EBV genome was not correlated with age, menopausal status, tumour, size, nodal status or histological grade. © 2001 Cancer Research Campaign http://www. bjcancer.com

Severe T-cell immunodeficiency after solid organ or bone marrow transplantation may result in the uncontrolled outgrowth of latently Epstein-Barr virus-infected B cells, leading to B-lymphoproliferative disorder (BLPD). Given the potentially important pathogenic role of IL-6 in BLPD, it was tested whether the in vivo neutralization of IL-6 by a monoclonal anti-IL-6 antibody could contribute to the control of BLPD. Safety and efficacy were assessed in 12 recipients of transplanted organs who had BLPD refractory to the reduction of immunosuppression over 8 days. Five patients received 0.4 mg/kg per day. The next 7 patients received 0.8 mg/kg per day. Treatment was scheduled to last 15 days. It was completed in 10 patients, and in the other 2 patients was discontinued early (days 10 and 13, respectively) because of disease progression. Treatment tolerance was good, and no major side effects were observed. High C-reactive protein levels were found in 9 patients before treatment but were normalized under treatment in all patients, demonstrating efficient IL-6 neutralization. Complete remission (CR) was observed in 5 patients and partial remission (PR) in 3 patients. Relapse was observed in 1 of these 8 patients in whom remission was observed. This relapse was unresponsive to treatment. Disease was stable in 1 patient, but it progressed in 3 patients. Seven patients are alive and well. Two patients died because of disease progression, and 3 patients died while in CR (chronic rejection in 2 patients and BLPD sequelae in 1 patient). These data suggest that the anti-IL-6 antibody is safe and should be further explored in the treatment of BLPD. (Blood. 2001;97: 1590-1597)

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