Epstein-Barr virus in breast cancer tissue and resistance to paclitaxel

1: J Virol. 2006 Jan;80(2):845-53. Links

Epstein-Barr Virus (EBV) Genome and Expression in Breast Cancer Tissue: Effect of EBV Infection of Breast Cancer Cells on Resistance to Paclitaxel (Taxol).

Arbach H, Viglasky V, Lefeu F, Guinebretiere JM, Ramirez V, Bride N, Boualaga N, Bauchet T, Peyrat JP, Mathieu MC, Mourah S, Podgorniak MP, Seignerin JM, Takada K, Joab I.

INSERM U716, IUH, IFR Saint-Louis, 27 rue Juliette Dodu, 75010 Paris, France. Irene.Joab@stlouis.inserm.fr.

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.

PMID: 16378986 [PubMed - in process]

[Lyn]

Hi there, does this article refer to having Epstein Barr Virus while on chemo or do the cells remain in the body indefinately. I once posted that Epstein Barr Virus (Glandular Fever) can cause breast cancer? and asked how many ladies had contracted it at some stage, but that thread died a natural death, on the old system, once a topic seems to reach the bottom of the page it is forgotten. I had Glandular Fever 2 years before I was lumbered with BC in 1998, but I did not know it at the time, my doc said that my blood work showed that I had contracted glandular fever within the last 12 months. I have also had Taxol and Taxotere, along with the anti convulsant drug Epelim which is believed to have impaired Taxanes and Cyclophosamides so is it any wonder I can't kick this demon, I have always believed that the big C is another virus, but like many others how do we kick it to the kerb.

Love & Hugs Lyn

[anne]

Hello Ladies,
I remember the EBV also causes Kaposi's Sarcoma in AIDS patients as well as HPV(human papilloma virus) is involved in cervical cancer. I wonder if this virus prays on peoples weak immune systems to cause some sort of cell mutation.

Anne

[CherylS]

This is interesting. I had heard that having mono, a result of the EBV quad-drupled chances of lymphoma, never heard about BC. I was diagnosed with mono approximately 1 1/2 years before BC. I wonder if there would be more response to this thread if people realize EBV typically becomes mono.

[Alice]

This is very interesting. I was diagnosed with EBV 25 years prior to my BC diagnosis. It seems like a bit of a stretch that it could be related but it would be something it had a connection. At the time chronic fatigue syndrome was the "In disease".It seemed when the doctors didn't have any answers thats what it was labled. When they told me I had chronic epstine barr and it signaled that I had a weak immune system and low T4 counts I just wrote it off to them not knowing what to tell me. It will be interesting to see if anything comes out of this.I will be keeping my eyes out for it.

[Camila]

Hi

My name is Camila and I joined the forum last night after months of sitting around in a "treatment haze" and trying to find some answers. Briefly, I was diagnosed with chronic fatigue syndrome in 2002 after a virus which was never identified, developed serious osteoarthritis over the next couple of years resulting in numerous joint replacements and surgeries and with HER2 3+++, oestrogen 2+ early BC with extensive vascular & 1 + lymph node late 2010. 2X lumpectomies then AC/taxol chemo X 8 and 2 doses herceptin now 30X radiation as treatment. Prior to herceptin my EF was 45% and my onc. still recommended herceptin (I did try to question him but was told it was OK). After only 2 infusions my EF dropped to 25% and I went into heart failure - very scary experience. Am now on numerous heart meds. and my cardiologist has told me after doing an echo. that I actually had viral cardiomyopathy BEFORE I had the herceptin. I saw a cardiologist 18mths before BC diagnosis with erratic heartbeat and always claimed the CFS virus had affected me, but no-one seems to believe me, although no-one can identify where the so-called viral cardiomyopathy came from. Needless to say, my not-so-subtle onc. has told me to "just get on the heart transplant queue" if I ever have any more doses of herceptin. I am feeling bitter with the medical profession and am devastated with no more herceptin. I agree with what you are saying about viruses. I was a very fit and healthy person until I got the virus, now I have severe arthritis, CFS, cancer and a weak heart. I am a "glass half full" person, but am finding it harder by the day and have been really down since being refused herceptin. You all sound like such an incredibly positive and loving group of ladies - thankyou so much for listening.

[Jackie07]

Hi Camila,

Epstein-Barr virus was a popular diagnosis in the past when doctors couldn't figure out the cause of CFS. I remember reading Gilda Radner's book (or perhaps someone else's) about it. Her doctor kept telling her that she'd gotten Epstein-Barr virus and was working too much...

I'm sorry for your heart problem. Several members on this Board have improved their heart function by exercising and taking enarlapri (?) I hope you can improve soon. My Herceptin treatment stopped at 4 weeks when MUGA dropped more than 10%. Even while I was on chemo, one of my knees was swollen (because my heart wasn't strong enough to pump the fluid back) after a 40-minute walk. I don't remember what my oncologist said about it, but he gave me weekly Herceptin (instead of every three weeks according to the protocol back in 2007) after chemo.

It might be possible that your CFS has partially been caused by your heart problem. The symptoms probably worsened when you were having breast cancer/and treatment. Have you had genetic testing done? Do you have any family members/relatives who have been diagnosed with cancer?

Tai-chi might be something you can do even with a weakened heart. It builds resistance, flexibility, ...etc.

Hope everything improves soon.

[Camila]

Hi Jackie,

Thanks for your quick reply. Funny you mention family cancer - I come from a HNPCC or Lynch syndrome family. My mum died from breast cancer and all her 5 sisters and brother (and father!) died from cancer too. This is why my BC was picked up early - because I have always kept up with my screenings due to the family history. Unfortunately I haven't been able to have genetic testing yet as I have to find a living relative who has had cancer, and sadly, I can't find anyone still alive. I see my cardiologist again tomorrow and I'm sure he will find I have improved as I can talk now without running out of breath. I sure plan to ask him if HE thinks I could ever go back onto herceptin (although I agree it might be some time yet).

Take care
Camila

[Jackie07]

My family seem to fall into the HNPCC category also. Mother is a 13 year Non-Hodgkins Lymphoma survivor, 2nd Brother (10 years my senior) is a 3-year colon cancer survivor. My brain tumor has been with me probably my whole life.

Be sure to try Tai-chi...

[Jackie07]

An abstract of the most recent research article on EBV:

Front Microbiol. 2011;2:5. Epub 2011 Jan 26.
Epstein-barr virus, the immune system, and associated diseases.

Chen MR.
Source

Epstein-Barr Virus Group, Graduate Institute and Department of Microbiology, National Taiwan University Taipei, Taiwan.

Abstract

Host immune system is designed (or evolved) to fight against different pathogens. Many viruses infect the immune cells for the propagation of new progenies, thus the infection may modulate the host immune homeostasis.

It has been more than 45 years since the discovery of Epstein-Barr virus (EBV) from a Burkitt's lymphoma derived cell line. The ability of EBV to transform primary B cells in vitro leads to the suggestion for its oncogenic potential. However, except the clear understanding of the role of EBV in post-transplantation lymphoproliferative disease, it remains ambiguous why such a ubiquitous virus causes malignant diseases only in a very small subset of individuals. Possible explanation is that EBV may cooperate with other environmental and host genetic factors and lead to the development of EBV associated neoplastic diseases.

In addition to infecting B cells, recent studies revealed that EBV may impact host immune system more broadly than previously thought, for example the development of regulatory NKT subsets. Instead of an intensive review, this article aims to provide a linkage to recent advances on the interplay between EBV and host immune system and to inspire further studies on EBV related diseases, especially autoimmune diseases.

[Camila]

Hi again Jackie,

Thanks for this citation - I have just ordered a copy of the full-txt online. Those of us who have suffered with devastating viruses know what they can do to a person physically, and I have always known that my immune system has been affected, hence the chronic fatigue syndrome now cancer. I will watch what others post with great interest.

Camila

[caya]

Very interesting. I had mono at age 40, diagnosed with BC 8 years later at age 48. I was very ill with the mono, and my GP told me that in her 15 year practice she only had one other patient over the age of 30 who had mono.

all the best
caya

[Lien]

Hi Camilla,

Perhaps I can reassure you a bit. I never had chemo or Herceptin, and am cancer free after 7.5 years. Not getting Herceptin doesn't have to be a problem. I think it's more important that you keep your heart in tip-top shape.

Jacqueline

[Lien]

Oh, and I was diagnosed with Chronic Fatigue Syndrome as well. Turned out to be caused by severe allergies I developed after a particularly nasty stomach bug picked up in Vietnam. If I stick to a very strict diet, I can function almost normally. If I ingest the wrong food or inhale the wrong substance, I'm totally wiped out.

Jacqueline