EB virus infected breast cancer cells may be less sensitive to chemotherapy

[Lani]

Epstein-Barr Virus Found in Breast Cancer Tissue May Impact Efficiency of Treatment [Eureka News Service]
Epstein-Barr virus has been detected in breast cancer tissue and tumor cells and may impact the efficiency of chemotherapeutic drug treatment say researchers from France and Japan. They report their findings in the January 2006 issue of the Journal of Virology.

A ubiquitous human herpesvirus, the Epstein-Barr virus (EBV), has been previously linked to skin and gastric cancer, as well as cancer of the salivary glands and thymus. New studies have detected EBV in breast cancer specimens and have prompted researchers to examine the effect of infection with EBV on anticancer drug treatment.

In the study biopsy specimens of breast cancer tissue and tumor cells were tested for the EBV genome. The genome was identified in about half of the specimens, however the viral load was highly variable from tumor to tumor. These findings indicate that although EBV isn't likely to cause breast cancer, it may contribute to tumor progression. In addition, researchers studied the EBV infected cells in vitro and found that the virus may contribute to the resistance of paclitaxel (taxol), chemotherapy commonly used in the treatment breast cancer, and cause overexpression of the multidrug resistance gene (MDRI).

"Consequently, even if a small number of breast cancer cells are EBV infected, the impact of EBV infection on the efficiency of anticancer treatment might be of importance," say the researchers.


ABSTRACT: Epstein-Barr Virus (EBV) Genome and Expression in Breast Cancer Tissue: Effect of EBV Infection of Breast Cancer Cells on Resistance to Paclitaxel (Taxol) [Journal of Virology; Subscribe]
The Epstein-Barr virus (EBV) has been detected in subsets of breast cancers. In order to elaborate on these observations, we quantified by real-time PCR (Q-PCR) the EBV genome in biopsy specimens of breast cancer tissue as well as in tumor cells isolated by microdissection. Our findings show that EBV genomes can be detected by Q-PCR in about half of tumor specimens, usually in low copy numbers. However, we also found that the viral load is highly variable from tumor to tumor. Moreover, EBV genomes are heterogeneously distributed in morphologically identical tumor cells, with some clusters of isolated tumor cells containing relatively high genome numbers while other tumor cells isolated from the same specimen may be negative for EBV DNA. Using reverse transcription-PCR, we detected EBV gene transcripts: EBNA-1 in almost all of the EBV-positive tumors and RNA of the EBV oncoprotein LMP-1 in a smaller subset of the tissues analyzed. Moreover, BARF-1 RNA was detected in half of the cases studied. Furthermore, we observed that in vitro EBV infection of breast carcinoma cells confers resistance to paclitaxel (taxol) and provokes overexpression of a multidrug resistance gene (MDR1). Consequently, even if a small number of breast cancer cells are EBV infected, the impact of EBV infection on the efficiency of anticancer treatment might be of importance.

[StephN]

Thanks, Lani, for the latest on this question.
Some time back we had this very question come up through some research by Lyn in Australia. Many of us responded that we have had the Mononeucleosis as a teen or tested positive for Epstein-Barr. It seemed like more than a small number within our HER2 breast cancer AND metastatic population.

The report says that the virus may contribute to the resistance of Taxol, but this was the drug that was GOOD for me (Adriamycin and Taxotere were totally ineffective) so may not be very active in my case.

Interesting that they are still persuing studying this virus in relation to cancers!

[Lani]

Robin P--what field of medicine is your husband in? perhaps he could comment on this? Or maybe Dr. Disis? I know breast cancer has many tricks to make the immune system less effective (causing apoptosis of dendritic cells, coating cytotoxic T lymphocytes in greasy muck so they are less effective,etc) but nasopharyngeal cancer is a notoriously difficult cancer to treat, so these results are impressive:

1: J Clin Oncol. 2005 Dec 10;23(35):8942-9. Epub 2005 Oct 3. Related Articles, Links

Cell therapy of stage IV nasopharyngeal carcinoma with autologous Epstein-Barr virus-targeted cytotoxic T lymphocytes.

Comoli P, Pedrazzoli P, Maccario R, Basso S, Carminati O, Labirio M, Schiavo R, Secondino S, Frasson C, Perotti C, Moroni M, Locatelli F, Siena S.

Laboratorio di Ricerca Area Trapianti e Oncoematologia Pediatrica, IRCCS Policlinico S. Matteo, V.le Golgi 19, 27100 Pavia, Italy. pcomoli@smatteo.pv.it

PURPOSE: Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-related malignancy expressing EBV antigens that are possible targets of cell therapy, including latent membrane protein 2 (LMP2). We conducted a clinical trial of EBV-targeted cell therapy with autologous virus-specific cytotoxic T lymphocytes (CTLs) for NPC refractory to conventional treatments. PATIENTS AND METHODS: Ten patients with EBV-related stage IV NPC in progression after conventional radiotherapy and chemotherapy received intravenously autologous EBV-specific CTLs reactivated and expanded ex vivo from peripheral blood lymphocytes through stimulation with EBV-transformed autologous B-lymphoblastoid cell lines (LCL). Toxicity, specific cellular immune responses, and clinical tumor responses were evaluated. RESULTS: EBV-specific CTLs could be generated in all patients and were predominantly CD3+/CD8+ T lymphocytes displaying specific killing of autologous EBV-LCL, autologous NPC cells as well as autologous targets bearing the EBV antigen LMP2. Patients received two to 23 infusions of EBV-specific CTLs that were well tolerated with the exception of grade 1 to 2 inflammatory reactions at the tumor site in two cases. Control of disease progression was obtained in six of 10 patients (two with partial response and four with stable disease). Analysis of interferon-gamma-producing cells demonstrated an increased frequency of EBV-specific immunity, with appearance of LMP2-specific responses in four patients, of whom three had clinical benefit. CONCLUSION: Cell therapy with EBV-targeted autologous CTLs is safe, induces LMP-2-specific immunologic responses, and is associated with objective responses and control of disease progression in patients with stage IV NPC resistant to conventional treatments.

Publication Types:

[Lyn]

Question, does the biopsy have to be tested for EBV or does it just show up anyway. I didnt know at the time I had it, it showed up in another test I had done later that I had the virus within the last 12 months, I seemed to build up a tolerence to this type of illness over the years becaue each time I thought I had it the blood test said know, I always suffered with tonsilitus and had them out at 8 but was still sick for years and told it was the tonsil remnants that made me sick, always got swollen glands, can remember being very sick that year but didn't bother to check it out, wouldn't you know the time I do get it I don't know about it. I have always thought that the big C is caused by a virus or viruses, we just drew the short straws in life.

Love & Hugs Lyn

[Lani]

the breast tumor itself has to be tested for the virus--here is more below:
Epstein-Barr Virus Found In Breast Cancer Tissue May Impact Efficiency Of Treatment

Category: Breast Cancer News
Article Date: 23 Jan 2006 - 0:00am (UK)






Epstein-Barr virus has been detected in breast cancer tissue and tumor cells and may impact the efficiency of chemotherapeutic drug treatment say researchers from France and Japan. They report their findings in the January 2006 issue of the Journal of Virology.

A ubiquitous human herpesvirus, the Epstein-Barr virus (EBV), has been previously linked to skin and gastric cancer, as well as cancer of the salivary glands and thymus. New studies have detected EBV in breast cancer specimens and have prompted researchers to examine the effect of infection with EBV on anticancer drug treatment.

In the study biopsy specimens of breast cancer tissue and tumor cells were tested for the EBV genome. The genome was identified in about half of the specimens, however the viral load was highly variable from tumor to tumor. These findings indicate that although EBV isn't likely to cause breast cancer, it may contribute to tumor progression. In addition, researchers studied the EBV infected cells in vitro and found that the virus may contribute to the resistance of paclitaxel (taxol), chemotherapy commonly used in the treatment breast cancer, and cause overexpression of the multidrug resistance gene (MDRI).

"Consequently, even if a small number of breast cancer cells are EBV infected, the impact of EBV infection on the efficiency of anticancer treatment might be of importance," say the researchers.

(H. Arbach, V. Viglasky, F. Lefeu, J.M. Guinebretiere, V. Ramirez, N. Bride, N. Boualaga, T. Bauchet, J.P. Peyrat, M.C. Mathieu, S. Mourah, M.P. Podgorniak, J.M. Seignerin, K. Takada, I. Joab. 2006. Epstein-Barr virus (EBV) genome and expression in breast cancer tissue: effect of EBV infection of breast cancer cells on resistance to paclitaxel (Taxol). Journal of Virology, 80. 2: 845-853.)

Carrie Patterson
cpatterson@asmusa.org
American Society for Microbiology
www.asm.org