Human Mammary Tumor Virus May Cause Breast Cancer?

maize · June 2012

Dr. Kathleen T. Ruddy's Breast Cancer Blog: The Breast Cancer Virus

"Four years ago I discovered research that has been hidden in the archives of medicine for more than seventy years: it appears that evidence of a breast cancer virus, the human mammary tumor virus, that is potentially involved with at least 40% of all breast cancer. Data show that women with the single most aggressive form of breast cancer, inflammatory breast cancer, show evidence of the virus in 75% of cases. This book is the story of my discovery of this virus and why I feel compelled to share this story with the three billion other women on the planet. Answering the question "Does a virus cause breast cancer in women?" could pave the way to a brand new world for breast cancer treatment and prevention."

http://breastcancerbydrruddy.com/?page_id=2149

A viral aetiology for breast cancer: time to re-examine the postulate.

"Two candidate viruses have been proposed, a human retroviral analogue of MMTV (which differs significantly in sequence and characteristics from HERs) and, the Epstein-Barr virus (gamma-herpes virus). These two viruses have been reported to occur in up to 37 and 50% of breast cancer cases, respectively. Here we present the background to the infectious hypothesis for the aetiology of breast cancer and review recent findings."

http://www.ncbi.nlm.nih.gov/pubmed/15044830

Increasing evidence for a human breast carcinoma virus with geographic differences

Paul H. Levine M.D.1,†,*, Beatriz G.-T. Pogo Ph.D.2, Afifa Klouj M.B.A.1, Stephanie Coronel M.P.H.3, Karen Woodson Ph.D., M.P.H.4, Stella M. Melana Ph.D.2, Nejib Mourali M.D.5,‡, James F. Holland M.D.2Article first published online: 12 JUL 2004

DOI: 10.1002/cncr.20436

Keywords:mammary tumor virus;breast carcinoma;epidemiology;wild mice
Abstract
BACKGROUND
An early immunologic study suggesting that a virus similar to the mouse mammary tumor virus (MMTV) was associated highly with breast carcinoma in Tunisian patients, compared with patients in the United States, led the authors to examine different breast carcinoma populations by using more current molecular techniques.
METHODS
Thirty-nine paraffin blocks were selected for sequencing of the 250-base pair segment of the MMTV from patients with breast carcinoma who were seen and treated at the Institut Salah Azaiz in Tunisia. Fifteen of those blocks were examined under code by a second laboratory, which used a different methodology and was blinded to the results of the first laboratory, and 14 blocks were analyzed successfully.
RESULTS
The comparison of Tunisian patients and patients from other countries clearly showed a significantly higher proportion of tumors with MMTV-like sequences in the Tunisian series of patients. There was complete reproducibility of data between the two laboratories. Using the results from the first laboratory and similar studies from the literature, detection of the MMTV-like env gene sequence showed an important geographic pattern with a significantly higher percentage of positive patients with breast carcinoma in Tunisia (74%) compared with patients with breast carcinoma in the United States (36%), Italy (38%), Australia (42%), Argentina (31%), and Vietnam (0.8%)
CONCLUSIONS
The findings provided increased evidence for a human breast carcinoma virus with geographic differences in prevalence. The geographic differences were compatible with studies of MMTV in wild mice; thus, the data were plausible biologically. Cancer 2004. © 2004 American Cancer Society.

http://onlinelibrary.wiley.com/doi/10.1002/cncr.20436/abstract

"In the last few years a number of labs have found MMTV like DNA in human breast cancer tissue and most recently, the virus has been shown to be able to productively infect human cells, possibly suggesting that an MMTV like virus may play a role in human breast cancer."

Mouse Mammary Tumor Virus
http://en.wikipedia.org/wiki/Mouse_mammary_tumor_virus

Mouse Mammary Tumor Virus Infects Human Cells

Stanislav Indik1,2, Walter H. Günzburg1,2, Brian Salmons3, and Francoise Rouault

The authors have found that retroviral sequences with 85% to 95% homology to the mouse mammary tumor virus were present in 40% of the sporadic breast cancers of American women. These sequences were not found in normal breasts or other tumors. A whole proviral structure was detected in 2 tumors. Breast cancer cells in culture were shown to contain and shed betaretroviral particles. This virus was designated human mammary tumor virus (HMTV). The authors have investigated the presence of HMTV sequences in a variety of breast conditions and geographic locations. Here they report that inflammatory breast cancer from American women shows a higher incidence of viral sequences (71%) than sporadic breast cancers. Similar incidence has been found in inflammatory breast cancers from Tunisia, and in gestational breast cancers. Because these conditions represent highly invasive malignancies, it is concluded that HMTV is sometimes associated with a particularly malignant phenotype. Cancer 2010;116(11 suppl):2741-4. © 2010 American Cancer Society.

Since Bittner1 described the mouse mammary tumor virus (MMTV) as the agent involved in mouse mammary carcinogenesis in 1936, MMTV has been regarded as a potential model for human disease.

http://cancerres.aacrjournals.org/content/65/15/6651.full

Human mammary tumor virus in inflammatory breast cancer†
Beatriz G.-T. Pogo MD1,‡,*, James F. Holland MD1, Paul H. Levine MD2Article first published online: 19 MAY 2010

DOI: 10.1002/cncr.25179

Copyright © 2010 American Cancer Society

http://onlinelibrary.wiley.com/doi/10.1002/cncr.25179/full

jenrio · June 2012

That's very very interesting. Thanks for sharing the link.

If a virus is behind it 40% of the time, it may mean a vaccine is a distinct possibility and antivirals may be devised against it. Even for the rest of us, a virus could be genetically engineered to set up virus factory inside any metastatic breast cancer and kill the cancer cells in a targetted way.

http://jnci.oxfordjournals.org/content/101/5/293.full

This article goes into the history of virus-cancer link. The "causal" link has proven hard to establish. But personally, I feel it's the potential treatment that is more interesting. I do not care whether it's 1% or 70% of breast cancer that is caused by this virus. I only care about how this virus could be turned into a targetted missile into the heart of this beast and make the cure possible.

"And Holland is addressing the missing link of temporality-whether infection precedes disease. His team is examining large libraries of breast tissue samples from the Nurses' Health Study, from which they will cull 300-400 samples from patients ultimately diagnosed with breast cancer, and 300 control samples, to determine whether HMTV infection precedes disease in women later diagnosed with breast cancer. Gunzburg's team is focusing on integration sites, and Pogo is investigating cells that are infected with HMTV, including lymphocytes, B cells, and T cells. She is also studying genes that are activated by the virus, as well as proteins that interact with the env gene."

Call for action. They need more samples! about 60% of pregnancy related cancers seem to be linked to MMTV and about 70% of IBC seem related to MMTV. So if your bc arose out of pregnancy or has IBC then you should consider donating samples.

maize · June 2012

Jenrio,

Since it's known that some cancers are linked to viruses--like Burkitt lymphoma--it seems to me it would be reasonable to suspect that some breast cancers might be caused by viral infection. As I understand it, infection with certain types of hepatitis virus can lead to liver cancer and infection with some strains of human papilloma virus can lead to cervical cancer.

Epstein-Barr virus

http://en.wikipedia.org/wiki/Burkitt's_lymphoma_virus

Oncovirus

Some viruses are tumorigenic when they infect a cell and persist as circular episomes or plasmids, replicating separately from host cell DNA (Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus). Other viruses are only carcinogenic when they integrate into the host cell genome as part of a biological accident, such as polyomaviruses and papillomaviruses."

http://en.wikipedia.org/wiki/Virus_cancer_link

Wouldn't there be the possibility of researchers working on a vaccine if there is evidence that some breast cancers may be caused by a virus, or that "cancer stem cells" are mutated and activated by a certain type of virus? A virus could cause a mutation,or more than one mutation, that causes the breast cancer, and that may be why evidence of the viruses named like HMTV are not found in the sample of women who don't have breast cancer.

I'm not a scientist, but it seems to me that if viruses can trigger certain cancers, or cause certain cancers, then it seems possible, or even likely, that a virus could trigger or actually cause breast cancers in some women--maybe in many cases. It could be that women who have what are considered hereditary cancers got them through transmission of a virus among family members--say the grandmother was unknowingly infected with a bc virus that caused a mutation and inadvertently passed it to her daughter who inadvertently passed it to her daughter.

jenrio · June 2012

Yes, virus do trigger certain cancers, the most well known example is cervical cancer as caused by HPV virus, can be prevented by a vaccine. In fact, for decades, scientists had looked for viral/bacterial causes of other cancers, and failed. So now, the mainstream oncologists think that most solid cancers are not CAUSED by virus.

However, if with new technologies, a virus is discovered that indeed cause a subset of breast cancers, say 1%, even 0.1%. It's still a very interesting discovery. Because virus that targets breast cells could be re-engineered to deliver a toxic payload (genetic code) into breast cancer cells. Now if turns out 40% of breast cancers are indeed viral related, then other new strategies can be devised against this kind of breast cancer because virus is foreign and can be targetted.

So, very interesting indeed.

maize · June 2012

Jenrio,

I think you're right that one of these viruses may not be implicated in all breast cancers, but it could be that one or both are implicated in some, and maybe are the cause of some types of breast cancer. A virus could cause a mutation that is unintentionally passed on to descendants for generations and is only activated (for some unknown reason) in certain female descendants. Maybe some viruses can switch off or shut down or eliminate the protective genes that block tumor-formation?

BaseballFan · June 2012

I think this might be related to Dr. Vincent Tuohys (cleveland clinic) breast cancer vaccine theory.

maize · June 2012

I've been looking at this; some of the info is so technical, but I think there have been efforts to use immunology and to try to stop cancer tumors from making their own vessels:

Vincent K. Tuohy
Development of Therapeutic Cancer Vaccines
Lerner Research Institute
Cleveland Clinic Foundation

p53 Tumor Suppressor

http://en.wikipedia.org/wiki/P53

I read that this p53, if it is messed up, doesn't work to stop tumor growth and is involved in some breast cancers.

Angiogenesis

"Cancer cells are cells that have lost their ability to divide in a controlled fashion. A tumor consists of a population of rapidly dividing and growing cancer cells. Mutations rapidly accrue within the population. These mutations (variation) allow the cancer cells (or sub-populations of cancer cells within a tumor) to develop drug resistance and escape therapy. Tumors cannot grow beyond a certain size, generally 1-2 mm3,[26] due to a lack of oxygen and other essential nutrients.

Tumors induce blood vessel growth (angiogenesis) by secreting various growth factors (e.g. VEGF). "

http://en.wikipedia.org/wiki/Angiogenesis

Judah Folkman
http://en.wikipedia.org/wiki/Judah_Folkman

Tumor antigen
http://en.wikipedia.org/wiki/Tumor_antigen

Human Mammary Tumor Virus May Cause Breast Cancer?

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