The Pink VirusDoes a Virus Cause Breast Cancer in Women?

By Dr. Kathleen Ruddy, MDFounder and President, Breast Health & Healing Foundation www.breasthealthandhealing.org

Copyright 2009 Kathleen T. Ruddy, MD, September 2009All rights reserved. No part of this presentation may be used or reproduced in any manner whatsoever without the written permission of Dr. Kathleen T. Ruddy who asserts her moral right to be identified as the author of this work in accordance with United States copyright law.

CONTENTSPART I - Slides 1-36:

A brief summary of the research regarding the mammary tumor virus, aka Pink Virus. The material is taken from articles published in peer-reviewed journals since 1936.

PART II - Slide 37:

Précis of the Breast Cancer Summit for The Pink Virus Project - October 9, 2009

Scientific Presentation:  Dr. Paul Levine, Professor, GWU, Washington, DCScientific Presentation:  Dr. Beatriz Pogo, Professor, Mt. Sinai University, NYCScientific Presentation: Dr. Polly Etkind, Virologist, Montefiore Medical Center, NYCFollowed by Comments on Presentation:  Dr. Fatah Kashanchi, Retrovirologist, GWU,

Washington, DC

PART III - Slide 43:

Bibliography of research, both pro and con, regarding the mammary tumor virus.

The PINK Virus PART I

This is the story of the discovery and research on the mammary tumor virus, aka Pink Virus, over the past seventy years.

As of 2009, hundreds of researchers have studied the mammary tumor virus; at least seven separate groups have found viral gene sequences in human breast cancer tissue and have reported their findings in articles published in peer-reviewed journals. 

One group reported that the virus originally found in mice, mouse mammary tumor virus (MMTV), has a human equivalent, human mammary tumor virus (HMTV), that can infect and spread rapidly among normal human breast cells.

Brower V,JNCI News, Vol. 101,Issue 5, March 4, 2009

Walter Gunzburg, Ph.D, Professor of Virology, Veterinary University of Vienna, JCNI News, Vol. 101, Issue 5, March 4, 2009

1936 - Dr. Bittner

Bittner J, Science, “Some Possible effects of nursing on the mammary gland tumor incidence inmice.” August 14, 1936, 84: 2171, p 162

In 1936, Dr. Bittner observed that when a strain of mice with a naturally high incidence of breast cancer breast-fed other mice with a low natural incidence of breast cancer, the rate of breast cancer in the low risk mice increased.

Bittner concluded that some infectious agent, which he called the “milk agent,” was transmitted from the high-risk mice to the low risk mice.

It was a truly revolutionary idea to hypothesize that cancer might be an infectious disease. Bittner’s discovery was a remarkable milestone, one that introduced a whole new way of thinking about one of the potential causes of human breast cancer.

1941 - Dr. Wooley

In 1941, Dr. Wooley noted that mice with a high incidence of breast cancer could lower their risk if they were fed milk from low risk mice.

Dr. Wooley then took some of the mice that had been fed from low risk mothers and injected them with the blood of high-risk mice that had not been so fed.

He observed that the transfusion of high-risk mouse blood into the lower risk mice increased the incidence of breast cancer once again.

Wooley, G. W., Law, L. W., and Little, C. C., Cancer Res., 1, 955, 1941

1942 - Dr. Bittner

Bittner J, The Milk-Influence of Breast Tumors in Mice, Science, 1 May 1942, 95:462-463

In 1942, Dr. Bittner did a similar experiment to Dr. Wooley when he fed, or injected, low risk mice with the “milk agent” from the high-risk mice.

Again, the low risk mice showed an increased incidence of breast cancer after they were so exposed.

1943/1946 - Dr. BittnerIn 1943, Dr. Bittner observed that his “milk agent” could be passed via breast milk, from high-risk mice to low risk mice.

By 1946, technology has advanced sufficiently for Dr. Bittner to proclaim that his “milk agent” was, in fact, a virus.

Bittner continued his experiments, expanding his animal studies to include rabbits. Dr. Bittner created a powder from his “milk agent” virus and injected it into rabbits. The rabbits did not develop breast cancer! However, after the injection, Dr. Bittner drew blood from the injected rabbits and put the blood into a test tube in which mouse breast cancer cells were growing. The breast cancer cells stopped growing!

Dr. Bittner concluded that the rabbits had developed immunity to the virus and that this immunity could be transferred to block the growth of mouse breast cancer cells.

Bittner, J. J., Cancer Res., 2, 710,1943

Bittner, J. J., and R. A. Huseby. 1946. Relationship of theinbred susceptibility and inherited hormonal influence in the development of mammary cancer in mice. Cancer Res. 6:235

1948 - Dr. Porter

In 1948, Dr. Porter looked at the mouse breast cancer cells using the recently invented electron microscope.

Dr. Porter observed viruses within the cancer cells, saying, “The findings are consistent with the view that the particles represent the milk agent.”

A PARTICULATE BODY ASSOCIATED WITH EPITHELIAL CELLS CULTURED FROM MAMMARY CARCINOMAS OF MICE OF A MILK-FACTOR STRAIN* BY KEITH R. PORTER, PhD., Am H. P. THOMPSON, M.D.~ From the Laboratories of The Rockefeller Institute for Medical Research, March 5, 1948

1958 - Dr. Bernharad

In 1958, Dr. Bernharad reviewed the published literature on MMTV and reported “virus-like particles were found in mouse mammary tumors constantly, in various laboratories on three continents.”

Bernhard, W., Electron microscopy of tumor cells and tumor viruses: a review, Cancer Research, 1958, 18, 491

In 1959, Dr. Moore of Rockefeller Institute in New York reported on his work irradiating the milk from high-risk mice to see what effect that might have.

He reported that irradiated milk produced more virus than milk from mice than had not been irradiated.

1958 - Dr. Moore

Correlation of Physical and Biological Properties of Mouse Mammary Tumor AgentDan H. Moore, J. Biophys. and Biochem. Cytol., Vol 5, 85-92, Copyright © 1959 by Rockefeller University Press

1963 - Dr. Chipchase

In 1963, Dr. Chipchase made the very important discovery that particles found in human breast milk possessed reverse transcriptase, the hallmark of the presence of all RNA retroviruses

Chipchase, M. Proceedings of the Natl Academy 49, 5, 692, 1963, 208

1971 - Dr. MooreIn 1971, Dr. Moore also reported that particles in human breast milk contained reverse transcriptase.

The discovery of reverse transcriptase in human breast milk proved that it was infected with a retrovirus, possibly one related to MMTV.

This was the first suggestion that MMTV might be involved in human breast cancer.

Nature 231, 97 - 100 (14 May 1971); doi:10.1038/231097a0

RNA-dependent DNA Polymerase Activity in Virus-like Particles isolated from Human MilkJ. SCHLOM*, S. SPIEGELMAN* & D. MOORE†

1970 - Dr. Gay

Gay F, Morphogenesis of Bittner Virus, Journal of Virology, June 1970, 5:801-816

In 1970, Dr. Gay was able to actually see MMTV forming within a breast cell and then emerging to be “swallowed up” by adjacent cells.

1972 - Dr. Axel

Axel R, Presence in Human Breast Cancer of RNA homologous to Mouse Mammary Tumour VirusRNA, Nature, 1972, 235:32-36

In 1972 the first bold statement about MMTV as an agent of human breast cancer was made by Dr. Axel:

“the results do provide the most compelling evidence available for the involvement of virus-related information in human breast cancer.”

Proc Natl Acad Sci U S A. 1972 November; 69(11): 3133–3137. Particles Containing RNA-Instructed DNA Polymerase and Virus-Related RNAin Human Breast CancersR. Axel, S. C. Gulati, and S. Spiegelman

1978 - Dr. Mesa-Tejada

Mesa-Tehada R, Detection in human breast carcinomas of an antigen immunologically related to agroup-specific antigen of mouse mammary tumor virus, Proc Natl Acad Sci USA, 1978,75:1529-1533

In 1978, Dr. Mesa-Tejada found a positive reaction to MMTV in 39% of human breast cancers examined; but found negative reactions in all benign breast tissue.

1981 - Dr. Day

Day N, Antibodies reactive with murine mammary tumor virus in sera of patients with breastcancer: Geographic and family studies, Proc Natl Acad Sci USA, 1981, 78:2483-2487

In 1981, Dr. Day reported that 18% of American women with a diagnosis of breast cancer that they examined showed positive evidence of MMTV in their blood.

However, when they examined normal, healthy women they found evidence of MMTV in only 2.8% of cases.

He concluded:

“Several possibilities must be considered to explain our findings, of which one is that a virus or viruses related to MMTV play a role in some patients with breast cancer.”

1981 - Dr. Witken

Witkin A, antigens and Antibodies Cross-Reactive to the Murine Mammary Tumor Virus in HumanBreast Cyst Fluids, J Clin Invest, 1981, 67:216-222

In 1981, Dr. Witken reported that he found components related to MMTV in 35% of benign breast cyst fluid, and went on to hypothesize that:

“perhaps additional genetic and/or environmental factors are needed to complete the transformation process to cancer.”

1983 - Dr. Peters

Peters G, Tumorigenesis by Mouse Mammary Tumor Virus: Evidence for a Common Region forProvirus Integration in Mammary Tumors, Cell, 1983, 33:36-377

In 1983, Dr. Peters reported his findings, suggesting that his research was:

“consistent with an insertional mutagenesis model for cancer formation by MMTV, in which integration of a provirus in a particular region of cellular DNA may activate a neighboring oncogene.”

He went on to say:

“Provirus integration can take place at multiple, possibly random sites.”

1984 - Dr. Westley

Westley B, The human genome contains multiple sequences of varying homology to mousemammary tumour virus DNA, Gene, 1984, 28:221-227

In 1984, Dr. Westley reported:

“there are many more MMTV-related sequences in human DNA than previously suggested.”

He thought perhaps:

“particular regions of chromosomal DNA act as preferred targets for provirus integration.”

1987 - Dr. Dion

Dion A, Retrovirus association with breast cancer: a critical appraisal, Breast Cancer Research andTreatment, 1987, 9:155-156

In 1987, Dr. Dion discussed his research, saying:

“Employing the insertional mutagenesis model, it is plausible to reconsider retrovirus-related agents as potential factors in the causation of human breast cancer.”

Dr. Dion went on to call researchers to:

“either confirm or nullify a retroviral association with breast cancer.”

1988 - Dr. Al Sumidaie

Sumidaie A, Particles with Properties of Retroviruses in Monocytes from Patients with BreastCancer, The Lancet, 1988, 5-9

In 1988, Dr. Al Sumidaie reported that 97% of breast cancer patients studied showed evidence of reverse transcriptase in their blood,

“strongly suggesting the presence of a retrovirus in patients with breast cancer.”

He concluded:

“The consistent association of MMTV in patients who have breast cancer suggests some causal association with the disease.”

1988 - Dr. Franklin

Franklin G, Expression of Human Sequences Related to Those of Mouse Mammary Tumor Virus,Journal of Virology, 1988, 62:1203-1210

In 1988, Dr. Franklin reported that:

“the expression of MMTV is hormonally regulated” and that “steroid hormones and their receptors may therefore contribute to the regulation of the expression of human MMTV-related retroviral sequences.”

1991 - Dr. Nusse

Nusse R, The int genes in mammary tumorigenesis and in normal development, TIG, 1988, 4: 10,291-295

In 1991, Dr. Nusse reported that insertion of MMTV into host DNA activated oncogenes. He characterized this as a

“mutagenic event for the host cell.”

He also suggested that MMTV genes could activate the transcription of other genes in the host DNA.

1993 - Dr. Shackleford

Shackleford G, Mouse mammary tumor virus infection accelerates mammary carcinogenesis inWnt-1 transgenic mice by insertional activation of int-1/Fgf-3 and hst/Fgf-4, Proc Natl Acad SciUSA, 1993, 90:740-744

In 1993, Dr. Shackleford stated that he

“believed that hormonal stimulation of mammary cell proliferation augments infection by, and production of, MMTV, thereby increasing the number of virus-infected cells and the likelihood of cancer.”

1994 - Dr. Golovkina

Golovkina T, Coexpression of Exogenous and Endogenous Mouse Mammary Tumor Virus RNA InVivo Results in Viral Recombination and Broadens the Virus Host Range, Journal of Virology,1994, 68:5019-5026

In 1994, Dr. Golovkina reported,

“retroviruses are subject to recombination with other endogenous retroviral genomes present in the same cell….As a result of the recombination events, new infectious retroviruses with altered biologic activities can be generated.”

1994 - Dr. Held

Held W, Reverse Transcriptase-dependent and –independent Phases of Infection with MouseMammary Tumor Virus: Implications for Superantigen Function, J Exp Med, 1994, 180:2347-2351

In 1994, Dr. Held reported that

“the immune reaction of the host, to infection by MMTV, triggered amplification of the virus and enhanced viral transmission throughout the host it infects.”

1994 - Dr. Imai

Imai S, Distribution of Mouse Mammary Tumor Virus in Asian Wild Mice, Journal of Virology,1994, 68:3437-3442

In 1994, Dr. Imai reported that several groups of wild mice, captured from eight different locations in Asia, showed only one strain that carried MMTV, and in that strain there was a 80-90% incidence of mammary tumor formation.

1997 - Dr. Pogo

Pogo B, Possibilities of a Viral Etiology for Human Breast Cancer, A Review, Biological TraceElement Research, 1997, 56:131-142

In 1997, Dr. Pogo found DNA sequences related to MMTV envelope gene in 39%of the breast cancer specimens she examined.

She reported:

“The virus does not carry a transforming oncogene, but rather acts as an insertional mutagen.”

2000 - Dr. Stewart

Stewart A, Identification of Human Homologues of the Mouse Mammary Tumor Virus Receptor,Archives of Virology, 147:577-581

Stewart T, Breast Cancer Incidence Highest in the Range of One Species of House Mouse, MusDomesticus, British Journal of Cancer, 2000, 82:446-451

In 2000, Dr. Stewart reported that the

“incidence of human breast cancer varies geographically….We found that the highest incidence of human breast cancer worldwide occurs in lands where mus domesticus (a species of mice) is the resident native or introduced species of house mouse.”

He went on to say:

“We propose that humans acquire MMTV from mice.”

2001 - Dr. Garry

In 2001, Dr. Garry reported:

“we are determining the incidence of HMTV in populations of breast cancer patients….HMTV may provide a target for vaccine development and breast cancer therapy.”

Garry, R.F. Human Mammary Tumor Virus: An Update. In: Hellenic Society for Breast Cancer Research Symposium Report (N.J. Agnantis, Ed.) Synedron Press (Athens, Greece), 15-19, 2001

2001 - Dr. Lawson

Lawson J, From Bittner to Barr: a viral, diet and hormone breast cancer aetiology hypothesis,Breast Cancer Res, 2001, 3:81-85

In 2001, Dr. Lawson from New South Wales reported that:

“the morphological characteristics of the viral particles in both the human and mouse milks appear to be almost identical and are unique. . . When these characteristics are considered in conjunction with the 98% similarity to the nucleotide sequences between HMTV and MMTV, it appears likely that these viruses are variants of each other.”

2001 - Dr. Lawson

Lawson J, From Bittner to Barr: a viral, diet and hormone breast cancer aetiology hypothesis,Breast Cancer Res, 2001, 3:81-85

In 2001, Dr. Lawson also pointed out “studies of human breast cancer cell lines have shown that administration of estrogen followed by progesterone stimulates the expression of human endogenous retroviruses in the genome.”

Furthermore, “...this evidence suggests that HMTV, and possibly other transmissible viruses, in association with diet, steroid and other hormones and genetic susceptibility, has a role in human breast cancer carcinogenesis…

...Many of these possibilities were suggested nearly 30 years ago…if the above hypotheses are shown to be true, then there is a possibility of primary prevention by dietary intervention aimed at reduction in serum estrogens, vaccine immunization for viral infections, and the use of hormone-modifying agents such as taxomifen for women with HMTV... All of these hypotheses are testable.”

2007 - Dr. Melana

Melana S, Characterization of viral particles isolated from primary cultures of human breast cancercells, Cancer Res, 2007, 67:8960-8965

In 2007, Dr. Melana reported that complete proviral structures of a retrovirus were found in human breast cancer cells.

They referred to this provirus as HMTV and found that it was 95% similar to MMTV and that it revealed features of a replication-competent virus.

Dr. Melana also reported finding viral sequences in the DNA of patients with metastatic breast cancer cells floating in the fluids in their lungs and abdomen.

When theses viral sequences were examined by electron microscopy they found the retroviral particles themselves, expressing envelope protein.

They declared: “These results clearly show that breast cancer cells in primary cultures produced HMTV viral particles that are similar to MMTV and which may play a role in breast cancer pathogenesis.”

The PINK Virus PART II

In 2008, Dr. Ruddy, Founder and President of the Breast Health & Healing Foundation, created its first initiative, the Pink Virus Project, to raise awareness about the possible link between the mammary tumor virus and human breast cancer.

On October 9, 2009, Dr. Ruddy convened the first collaborative meeting on the subject of the mammary tumor virus, the Breast Cancer Summit for the Pink Virus Project. This ground-breaking meeting was held in the Senate Russell Building on Capitol Hill and brought together scientists from across the country who have been working on the mammary tumor virus for decades. It gave them them the opportunity to present and discuss their research with other scientists, representatives from other breast cancer foundations, hospital administrators, patient advocates, staff and legislative aides of Members of Congress, and the most important guests of all -- breast cancer survivors and their families.

October 9, 2009Washington, D.C.

Scientific Presentation:  Dr. Paul Levine, Professor, GWU, Washington, DC

Dr. Levine began by reviewing the existing proof of viral causes of human cancer:  human papilloma virus and cervical cancer, hepatitis virus and liver cancer, Epstein-Barr virus and Burkitt’s lymphoma. 

Dr. Levine’s own research shows evidence of the mammary tumor virus in more than 70% of women with Inflammatory Breast Cancer in Tunisia. 

Dr. Levine also reported that in one study of women in the United States with inflammatory breast cancer there was also evidence of the mammary tumor virus in over 70% of cases. 

Dr. Levine recommended two additional studies to enlarge these data, one in the United States and one in Africa where Inflammatory Breast Cancer is much more common.

October 9, 2009 - Précis of the Breast Cancer Summit for The Pink Virus Project

Levine. “Increased incidence of mouse mammary tumor virus-related antigen in Tunisian patientswith breast cancer.” Int. J. Cancer 33 (1984): 305-308.

Scientific Presentation:  Dr. Beatriz Pogo, Professor, Mt. Sinai University, NYC

Dr. Pogo's research shows evidence of mammary tumor virus in 39% of all women with breast cancer that she tested. 

Of note:  there was no evidence of the virus in normal tissue from these patients, strengthening the evidence that the virus may be involved in the development of breast cancer. 

Over 90% of the women with evidence of the virus in their breast tumors also showed evidence of the virus in their bloodstream. 

Of the women Dr. Pogo studied who developed breast cancer during pregnancy, over 60% of them showed evidence of the mammary tumor virus. 

October 9, 2009 - Précis of the Breast Cancer Summit for The Pink Virus Project

Scientific Presentation: Dr. Polly Etkind, Virologist, Montefiore Medical Center, NYC

Dr. Ekind’s independent research also shows evidence of mammary tumor virus in 37% of all women with breast cancer she tested. 

Dr. Etkind also found evidence of the mammary tumor virus in women who had both breast cancer and non-Hodgkin’s lymphoma. 

Dr. Etkind discussed the higher rate of non-Hodgkin’s lymphoma in women with a prior history of breast cancer and the possible involvement of the mammary tumor virus in both diseases.

October 9, 2009 - Précis of the Breast Cancer Summit for The Pink Virus Project

Etkind. P, “Mouse mammary tumor virus-like ENV gene sequences in human breast tumors and in alymphoma of a breast cancer patient.” Clin Can Res (2000):1273-78

Comments on Presentation:  Dr. Fatah Kashanchi, Retrovirologist, GWU, Washington, DC

Dr. Kashanchi, a well-respected virus researcher with multiple grants from the NIH/NCI, offered his questions and comments at the conclusion of the scientific presentations. 

He stated that the research of Drs. Levine, Pogo and Etkind were well done and compelling and that "they were on to something" with regard to the possible involvement of the mammary tumor virus and human breast cancer. 

He suggested additional research studies directed at augmenting and broadening the research done thus far.

October 9, 2009 - Précis of the Breast Cancer Summit for The Pink Virus Project

The question remains open:  Is a virus involved in human breast cancer?

Research findings and future announcements will be reported through the Pink Virus Project, an initiative of the Breast Health & Healing Foundation.

Breast Health & Healing, through its website and Dr. Ruddy’s social networking venues, will keep the public updated on the progress that is made researching the link between the mammary tumor virus and human breast cancer.

www.breasthealthandhealing.org

November 1, 2009

The PINK Virus PART III

BibliographyFurther reading: research papers on the mammary tumor viruses, MMTV and HMTV.

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Bittner J, The Milk-Influence of Breast Tumors in Mice, Science, 1 May 1942, 95:462-463

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Gay F, Morphogenesis of Bittner Virus, Journal of Virology, June 1970, 5:801-816

Golovkina T, Coexpression of Exogenous and Endogenous Mouse Mammary Tumor Virus RNA In Vivo Results in Viral Recombination and Broadens the Virus Host Range, Journal of Virology, 1994, 68:5019-5026

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