The Fire Storm on Mammographic Screening Reaches the White House

Mammographic screening saves lives, at every age, even when screening begins at age forty.  Given that 15% of the breast cancers that are diagnosed in women in their forties are found by screening mammogram, and given that at least 75% of these patients have no risk factors for breast cancer whatsoever, (other than being female), it is clear that mammographic screening, beginning at age forty, makes sense even for younger women.

 

It is no wonder the new recommendations from the Health and Human Services’ U.S. Preventive Services Task Force, to abandon annual screening mammography for women in their forties, and reduce screening of women over fifty to every two years instead of every year, set off a fire storm of opposition from women and institutions alike.

 

Fortunately, at least two members of Congress are leading the charge to revisit the recommendations of the Task Force.  Representative Debbie Wasserman-Schultz of Florida, who was diagnosed with breast cancer at the age of 41, said that she is outraged by the new recommendations.  Representative Frank Pallone of the House Energy and Commerce subcommittee on Health has decided to hold a hearing about the Task Force’s new guidelines, a hearing at which Representative Wasserman-Shultz hopes that the guidelines will be set aside.  Amen.

 

The hearing proposed by Representative Pallone is more than just an appropriate response to the recommendations of the Task Force, it is a vitally important political maneuver.  You see, the Secretary of Health and Human Services, Ms. Sebelius, in an effort to smother the flames of opposition against the new recommendations of the Task Force (a committee that ultimately reports to her), announced today that the Task Force does not make policy.  Right.  But the Task Force was given the responsibility to advice HHS on policy, specifically recommending whether, and under what circumstances, screening mammograms are deemed to be appropriate based on the experts’ critical review of the literature, aka “evidence-based medicine.”

 

For Ms. Sebelius to say that the Task Force was assigned the job of making recommendations, and then to say that they have no power to make policy is not back-pedaling on the issue, it is falling off the bike entirely.  Furthermore for Ms. Sebelius and the Task Force to suggest that women “talk to their doctors” is insulting, both to patients and their doctors.  What, exactly, are they to discuss?  The literature?

 

The data are clear:  mammograms save lives, at every age.  Women don’t need to talk to their doctors, women need to talk to their government:  tell those who represent us to provide screening mammograms for all women, beginning at age 40, unless and until they can provide a better screening test for breast cancer.

 

If you want a test that is more cost-effective, guess what, so do we.  Fund that, not another review of the literature.  The data are not going to change, so if you want to save money and fulfill the public’s expectation that our healthcare system save lives, then help us find a better test, don’t tell us to abandon the only one we have that works.

Screening Mammography: Annually, Beginning at Age 40

Annual screening mammography, beginning at age 40, prevents death from breast cancer. This truth has not changed with the recent review of the literature just reported by the US government.

Yes, screening mammograms discover abnormalities that require further investigation, sometimes involving biopsy, and often are ultimately found to be benign.  So do chest x-rays.  So do EKGs.  So do PAP smears.  But, better to find something that is benign than not find something that is malignant, particularly if finding a malignancy early saves lives, which it does.

Of course, annual mammography is tedious, expensive and, on occasion, associated with a fair amount of grief and aggravation.  But so is death from breast cancer.

The earth is still round, and annual screening mammography, beginning at age 40, still saves lives.  If the smartest minds in the room want to make a recommendation regarding the current guidelines for screening mammography, then let them insist that a better screening test be developed as soon as possible, not recommend that the best screen we have be adopted only when the cost-benefit ratio is high enough to make a big impression around the table.

One life saved is a big enough impression for me.

Updated Bibliography of Research on the Mammary Tumor Virus

I will be posting revisions to the bibliography for my book, The Pink Virus:  Does a Virus Cause Breast Cancer in Women?

Here is the most recent update.  This won’t be of interest to the general reader, but it might be very helpful for any viewer (researcher, journalist) who is in need of references.  It took me the better part of three months to gather these references, so I do hope that this list will be useful as a source for others who are interested in this most interesting subject.

To wit:

Bibliography

Andersson A, Expression of human endogenous retrovirus ERV3 (HERV-R) mRNA in normal and neoplastic tissues, Int J Onc, 1998, 12: 309-313

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

Benit L, Identification, Phylogeny, and Evolution of Retroviral Elements Based on Their Envelope Genes, J Virology, 2001, 75: 23, 11709-11719

Bera T, Defective Retrovirus Insertion Activates c-Ha-ras Proto-oncogene in an MNU-Induced Rat Mammary Carcinoma, Biochem Biophy Res Comm, 1998, 248: 835-840

Berkhout B, Identification of an Active Reverse Transcriptase Enzyme Encoded by a Human Endogenous HERV-K Retrovirus, J Virology, 1999, 73: 3, 2365-2375

Bittner J, Science, August 14, 1936, 84: 2171, p 162

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

Bock M, Endogenous retroviruses and the human germline, Current Opinions in Genetics & Development, 2000, 10: 651-655

Chopra H, Cancer Research, 1970, 30: 8, 2081-2086

Callahan R, Detection and cloning of human DNA sequences related to the mouse mammary tumor virus genome, Proc Natl Acad Sci USA, 1982, 79:5503-5507

Casey, G., Characterization and chromosome assignments of the human homolog of int-2, a potential protooncogene. Mol and Cell. Biol.  1986, 6, 502-510

Crepin, M., Sequences related to mouse mammary tumor virus genome in tumor cells and lymphocytes from patients with breast cancer, Biochem. Biophysic, Res. Comun., 118, 1984, 324-331

Dalton A, Some Ultrastructural Characteristics of a Series of Primary and Transplanted Plasma-Cell Tumors of the Mouse, JNCI, 1961, 26: 5, 1221-1266

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

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

Faff, O, Retrovirus-like particles from the human T47D cell line are related to mouse mammary tumor virus and are of endogenous origin, J. Gen. Virol. 73, 1992, 1087-1097

Fennelly J, Co-amplification of tail-to-tail copies of MuRVY and APE retroviral genomes on the Mus musculus Y Chromosome, Mammalian Genome, 1996, 7: 31-36

Ford, CE, Mouse mammary tumor virus-like gene sequences in breast tumors of Australian and Vietnamese Women, Clinical Cancer Research, 2003, Vol 9: 1118-1129

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

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

Gray D, Activation of int-1 and int-2 Loci in GRf  Mammary Tumors, Virology, 1986, 154: 271-278

Griffiths D, Endogenous retroviruses in the human genome sequence, Genome Biology, 2001, 2: 6, 1017.1-1017.5

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

Holland J, Breast Cancer Res Treat, 2006, 100:Absract 6

Hughes J, Evidence for genomic rearrangements mediated by human endogenous retroviruses during primate evolution, Nature Genetics, 2001, 29: 487-489

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

Indik, S, Mouse mammary tumor virus infects human cells, Cancer Research, 2005, 65, 6651-6659

Indik, S, Rapid spread of mouse mammary tumor virus in cultured human breast cells, Retrovirology, 2007, 4, 73

Karlsson H Retroviral RNA identified in the cerebrospinal fluids of brains of individuals with schizophrenia, PNAS, 2001, 98: 8, 4634-4639

Keydar I, Properties of retrovirus-like particles produced by a human breast carcinoma cell line:  Immunological relationship with mouse mammary tumor virus proteins, Proc. Natl. Acad. Scie, USA 81, 1984- 4188-4191

Larson E, Human Endogenous Proviruses, Current Topics in Microbiology and Immunology, 1989, 148:115-132

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

Lawson, J, Do viruses cause breast cancer Methods Mol Biol, 2009, 471: 421-38

Leib C, Endogenous Retroviral Elements in Human DNA, Cancer research (Supp), 1990, 50:5636-5642

Lejueune S., Wnt5a cloning, expression and up-regulation in human primary breast cancer. Clin. Cancer Res. 1, 1995, 215-222

Levine P, Immunopathologic features of rapidly progressing breast cancer in Tunisia, Proc. Am. Assoc. Cancer Res. 21, 1980, 170

Lidereau R., Amplification of the int-2 gene in primary human breast tumors. Oncogene Res. 2, 1988, 285-291

Links J, The Growth Accelerating Effect of Bittner Virus in Monolayers of Baby Mouse Kidney Cells, J. Gen Virol, 1969, 5:547-550

Liscia D., Expression of int-2 mRNA in human tumors amplified at the int-2 locus. Oncogene 4, 1989, 1219-1224

Litvinov S, Expression of proteins immunologically related to murine mammary tumour virus (MMTV) core proteins in the cells of breast cancer continuous lines MCF-7, T47D, MDA-231 and cells from human milk, Acta Virologica 33, 1989, 137-142

Lloyd R, Murine mammary tumor virus related antigen in human male mammary carcinoma, Cancer 51, 1983, 654-661

Lower R, A General Method for the Identification of Transcribed Retrovirus Sequences (R-U5 PCR) Reveals the Expression of the Human Endogenous Retrovirus Loci HERV-H and HERV-K in teratocarcinoma Cells, Virology, 1992, Virology, 192: 501-511

Lower R, The pathogenic potential of endogenous retroviruses:  facts and fantasies, Trends in Microbiology, 1999, 7: 9, 350-356

MacArthur C. Fgf-8, activated by proviral insertion, cooperates with the Wnt-1 transgene in murine mammary tumorigenesis, J. Virol. 69, 1995, 2501-2507

Mager D, HERV-H Endogenous Retroviruses:  Presence in the New World Branch but Amplification in the Old World Primate Lineage, Virology, 1995, 213: 395-404

Mager D, Novel Mouse Type D Endogenous Proviruses and ETn Elements Share Long Terminal Repeat and Internal Sequences, J Virology, 2000, 74: 16, 7221-7229

Marchetti A, Host Genetic Background Effect o the Frequency of Mouse Mammary Tumor Virus-Induced Rearrangements of the int-1 and int-2 Loci in Mouse Mammary Tumors, J Virology, 1991, 65: 8, 4550-4554

Marrack P, A maternally inherited superantigen encoded by a mammary tumour virus, Nature, 1991, 349:524-525

McGrath C, J Virology, 1972, 9: 2, 367-376

Medina D, Selenium-mediated inhibition of mouse mammary tumorigenesis, Cancer Lett. 8, 1980, 241-245

Medstrand K., Expression of human endogenous retroviral sequences in peripheral blood mononuclear cells of healthy individuals, Gen. Virol. 73, 1992, 2463-2466

Medstrand K., Characterization of novel reverse transcriptase encoding human endogenous retroviral sequences similar to type A and type B retroviruses:  Differential transcription in normal human tissues, J. Virol. 67, 1993, 677-6787

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

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

Mueller-Lantzsch N, Human Endogenous Retroviral Element K10 (KERV-K10) Encodes a Full-Length Gag Homologous 73-kDa Protein and a Functional Protease, AIDS Research and Human Retroviruses, 1993, 9: 4, 343-350

Mukhopadhyay R, Expression of the mouse mammary tumor virus long terminal repeat open reading frame promotes tumorigenic potential of hyperplastic mouse mammary epithelial cells, Virology 211, 1995,84-93

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

Nusse R, Insertional Mutagenesis in Mouse Mammary Tumorigenesis, Current Topics in Microbiology and Immunology, 1991, 171:43-65

Ono M, Stimulation of Expression of the Human Endogenous Retrovirus Genome by Female Steroid Hormones in Human Breast Cancer Cell Line T47D, Journal of Virology, 1987, 61:2059-2062

Paces J, HERVd:  database of human endogenous retroviruses, Nucleic Acids Research, 2002, 30: 1, 205-206

Palmarini M, The Exogenous Form of Jaagsiekte Retrovirus Is Specifically Associated with a Contagious Lung Cancer of Sheep, J of Virology, 1996, 70: 3, 1618-1623

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

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

Prak E, Mobile Elements and the Human Genome, Nature Reviews Genetics, 2000, 1: 134-144

Reus K, HERV-K (OLD):  Ancestor Sequences of the Human Endogenous Retrovirus Family HERV-K (HNL-2), J Virology, 2001, 75: 19, 8917-8926

Reuss F, cDNA Sequence and Genomic Characterization of Intracisternal A-Particle-Related Retroviral Elements Containing an Envelope Gene, J Virology, 1991, 65: 11, 5702-5709

de Ricqles D., Breast cancer and T-cell mediated immunity to proteins of the mouse mammary tumour virus (MMTV), Eur. Cytokine Netw. 4, 1993, 153-160

Ross SR, Is there a breast cancer-causing virus in humans? The Ribbon, Vol 5, Issue 3, Early Fall 2000, Cornell University

Schrauzer G, Effects of selenium and of arsenic on the genesis of spontaneous mammary tumors in inbred C3H mice, Ann. Clin. And Lab. Sci, 4, 1974, 441-447

Schrauzer G., Inhibition of the genesis of spontaneous mammary tumors in C3H mice:  Effects of selenium and of selenium-antagonistic elements and their possible role in human breast cancer, Bioinorg. Chem. 6, 1976, 265-270

Segal-Eiras A, Antibodies presumably cross-reacting with mouse retrovirus type B and C in the sera of both leukemia-lymphoma and mammary cancer patients, Arch. Geschwulstforsch, 53, 1983, 321-327

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

Smit A, Interspersed repeats and other mementos of transposable elements in mammalian genomes, Current Opinion in Genetics & Development, 1999, 9: 657-663

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, Mus Domesticus, British Journal of Cancer, 2000, 82:446-451

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

Szabo S, Of Mice, Cats and Men:  Is human breast cancer a zoonosis? Microsc Res Tech, 2005, 68:197-208

Szakaacs J., Sequence homology of deoxyribonucleic acids to mouse mammary tumor virus genome in human breast tumors, Ann. Clint. Lab. Scie, 21, 1991, 402-412

Tchenio T, Defective Retroviruses Can Disperse in the Human Genome by Intracellular Transposition, Journal of Virology, 1991, 65:2113-2118

Time, Cancer Virus, March 18, 1946

Tonjes R, Characterization of Human Endogenous Retrovirus Type K Virus-like Particles Generated from Recombinant Baculoviruses, Virology, 1997, 233: 280-291

Tristem M, Identification and Characterization of Novel Human Endogenous Retrovirus Families by Pylogenetic Screening of the Human Genome Mapping Project Database, J Virology, 2000, 74: 8, 3715-3730

Turner G, Insertional polymorphisms of full-length endogenous retroviruses in human, Current Biology, 2001, 11: 1531-1535

Wang Y, Detection of mammary tumor virus env gene-like sequences in human breast cancer, Cancer Res. 55, 1995, 5173-5179

Wang Y., Identification and expression of MMTV-like sequences in human breast cancer, Proc. Am. Assoc. Cancer Res. 37, 1996, 565

Wang Y, Detection of MMTV like LTR and LTR-env gene sequences in human breast cancer, Int J Oncology, 2001, 18: 1041-1044

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

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

Yanagawa S, Identification of a novel mammary cell line-specific enhancer element in the long terminal repeat of mouse mammary tumor virus, which interacts with it hormone-responsive element, J. Virol, 67, 1993, 112-118

Zhou D., Amplification of human int-2 in breast cancers and squamous carcinomas, Oncogene 2, 1988, 279-282

Zotter S, Mouse Mammary Tumour Virus-related Antigens in Core-like Density Fractions from Large Samples of Women’s Milk, Euro J Cancer, 1980, 16:455-467

More Good News About the Declining Use of HRT

Impact of Hormone Replacement Therapy

On Premalignant Changes in the Breast

 

 

Approximately 85% of breast cancers arise from cells that line the milk ducts of the breast.  But most of these cancers do not arise “overnight;” instead, they tend to develop over time in a progression from “normal” through various stages of increasing abnormality until, finally, they acquire the three characteristics of cancer cells:  immortality, invasiveness, metastasis.

 

One of the steps along the path from normal to cancer is a distinct phase known as atypical ductal hyperplasia.  Such cells appear abnormal when viewed under the microscope, (which is how the diagnosis is made), but they are also abnormal in terms of their DNA:  their genes are altered and headed in the direction of malignant transformation.

 

Women who are diagnosed with atypical ductal hyperplasia have a 3-5 times increased risk for breast cancer.  Thus, the finding of atypical ductal hyperplasia is considered a trigger for increased surveillance in women who are diagnosed with it.

 

In recent years the declining use of hormone replacement therapy has been associated with a decline in the number of new cases of breast cancer.  It now appears that the declining use of hormone replacement therapy is also associated with a decline in the incidence of atypical ductal hyperplasia.

 

In a recent review of patients and 2.4 million mammograms performed between 1999-2005, researchers reported that the use of hormone replacement therapy fell from 35% in 1999 to 11% in 2005, while at the same time the incidence of atypical ductal hyperplasia fell from 5.5 to 2.4 (per 10,000 cases.)  It is therefore reasonable to expect that the reduction, by half, of the incidence of atypical ductal hyperplasia (from 5.5 to 2.4) will similarly reduce the number of new cases of breast cancer that arise by this path.

 

Whatever else can be made of the data reported in this study, one fact takes obvious and overwhelming precedence:  the declining use of hormone replacement therapy is a good thing.

 

It is now abundantly clear that avoiding hormone replacement therapy is one of the simplest ways to reduce both the incidence and the propensity for breast cancer.  In these days when the most livid conversations are over healthcare reform, when political leaders can only dream of finding ways to bend the cost curve of medicine, here is an intervention – avoid hormone replacement therapy – that bends it quite nicely and, in so doing, yields longer, healthier lives.

 

Reference:  Menes, T. New Key to Puzzle of Hormone Therapy and Breast Cancer. Cancer Epidemiology Biomarkers & Prevention, November 11, 2009

Two New Powerpoint Presentations: The History of Research on the Pink Virus, and What is a Virus? What is Cancer? Is There A Virus Thought to Cause Breast Cancer?

The first presentation is a summary of the history of research on the mammary tumor virus.  It is pretty clear but packed with references, and it includes a pretty extensive bibliography at the end.

The second presentation, which the scientifically-challenged might find easier to digest, is a simple explanation for how viruses work, the nature of cancer cells, and the relation between the two.

Enjoy, and please leave comments and suggestions so that we can improve the slide show for others.

The Pink Virus

What is a Virus

Antiviral Therapy for Cancer Patients: Hope for a New Direction

Given that between 15-20% of all cancers are thought to be related to a virus (H. zur Hausen, Viruses in human cancers, Curr.Sci. 81, 2001, 523-527; D.M.Parkin, The global health burden of infection-associated cancers in the year 2002, Int. J. Cancer 118, 2006, 3030-3-044), and given that there is compelling and converging evidence that a mammary tumor virus may be involved in a significant portion of human breast cancer (V. Brower, Mouse mammary tumor virus:  new tumor virus of just a rumor virus? JNCI News, Vol. 101, Issue 5, March 4, 2009), the following article reporting positive results from a Canadian study that used the antiviral medication, ribavirin, in patients with a variety of cancers points the way, especially as regards the mammary tumor virus, for a new way of thinking and funding research.

Antiviral Therapy for Cancer Patients- Canadian Study

The Pink Virus: Does a Virus Cause Breast Cancer in Women?

This is a power point presentation I created today to help tell the story of the mammary tumor virus, aka the Pink Virus.  I hope it helps women understand why it is so important to get this question answered . . . without waiting another seventy years for the answer!

The Pink Virus

Women With Breast Cancer, Please Write on SHE WRITES.COM

I’ve just created a women’s writing group on a web site I discovered a few days ago and that I just love:  SHEWRITES.COM

Women with breast cancer, please write.

http://www.shewrites.com/group/womenwithbreastcancerwrite

 

Very Interesting Development re: Viruses/Cancer/Targeted Therapy

This just crossed my radar screen.  It is well worth sharing.  Feel free to ask questions; I will do my best to answer therm.

It is taken from Science Daily today, November 3:

(Nov. 2, 2009) — Targeted immunotherapy has been an attractive new therapeutic area for a number of cancers because it has the potential to destroy tumor cells without damaging surrounding normal tissue. New study results demonstrate high success rates using specialized white blood cells to prevent or treat lymphoma associated with the Epstein-Barr virus (EBV-lymphoma) in patients who have received a hematopoietic stem cell transplant (HSCT). This study was recently published online in Blood, the official journal of the American Society of Hematology.

 

Lymphoma is a cancer of white blood cells called lymphocytes that are largely responsible for maintaining the body’s immunity, and EBV is one of the most common human viruses that can have a long-lasting impact on the body’s immune system. Immune-compromised patients who receive HSCT, especially from mismatched donors or matched but unrelated donors, may be at higher risk of developing EBV-lymphoma than other patients. Previous studies have suggested that EBV-lymphoma occurs most often in the first few months post-transplant.

The researchers hypothesized that aggressive EBV-lymphomas may be responsive to control or eradication with EBV-specific cytotoxic T lymphocyte (CTL) treatment. (CTLs are highly specialized white blood cells that build the body’s defenses against disease.) To test their theory, the team infused EBV-specific CTL lines into two groups of patients: those who were undergoing HSCT and were at high risk of developing EBV-lymphoma, and patients who had already developed lymphoma. The study reported that CTL treatment successfully prevented the development of EBV-lymphoma in all 101 patients in the at-risk group who received the therapy prophylactically and achieved sustained complete remission in 11 of the 13 patients (85 percent) treated therapeutically (those who already had the disease).

“Therapy with EBV-specific CTLs was effective for these severely immunocompromised patients. The CTLs successfully reached tumors, multiplied, and were able to kill the tumor cells,” said lead study author Helen Heslop, MD, of the Center for Cell and Gene Therapy at Baylor College of Medicine, The Methodist Hospital, and Texas Children’s Hospital.

While the successful outcomes result from a number of factors in the study, the researchers attribute some of the success of the trial to the time of treatment. The CTL lines were infused soon after stem cell transplantation, when the existing white blood cell count was still low and was not quickly regenerating, allowing the infused cells to more quickly multiply and mediate anti-viral and anti-tumor effects. In addition, by marking and tracking the CTL genes, the team was able to demonstrate that the cells could survive for up to nine years in the body, conferring long-term protection.

With strong clinical outcomes, the study team is working to determine the most appropriate role and timing for CTL infusions. Some newer therapies (such as monoclonal antibodies) offer prophylactic and therapeutic options but cannot offer long-term protection. Therefore, treatment with CTLs may be reserved for the highest risk patients — those with a diagnosis of immune deficiency or a history of EBV-lymphoma, or those who develop elevated EBV levels after therapy with monoclonal antibodies.

Importantly, the study found that this type of therapy is not only effective, but economically advantageous. A preliminary analysis showed that a patient-specific CTL line can be manufactured, tested, and infused for approximately $6,000, a cost that compares well with other modalities used in the treatment of EBV-lymphoma. Moreover, the team determined that it is possible to manufacture cells in one location and ship them to another center for infusion, with reproducible and consistent results and clinical outcomes.

“It’s important to note that this promising therapy is not only effective, but it is also a cost-effective option for high-risk patients,” said Dr. Heslop.

 

Bibliography for the Mammary Tumor Virus

Many have asked for a reference list for the mouse and human mammary tumor virus.  Given below is an abbreviated, though not short, list.  For those who enjoy a good old-fashioned hunt, have fun!

 

Bibliography

 

Andersson A, Expression of human endogenous retrovirus ERV3 (HERV-R) mRNA in normal and neoplastic tissues, Int J Onc, 1998, 12: 309-313

 

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

 

Benit L, Identification, Phylogeny, and Evolution of Retroviral Elements Based on Their Envelope Genes, J Virology, 2001, 75: 23, 11709-11719

 

Bera T, Defective Retrovirus Insertion Activates c-Ha-ras Proto-oncogene in an MNU-Induced Rat Mammary Carcinoma, Biochem Biophy Res Comm, 1998, 248: 835-840

 

Berkhout B, Identification of an Active Reverse Transcriptase Enzyme Encoded by a Human Endogenous HERV-K Retrovirus, J Virology, 1999, 73: 3, 2365-2375

 

Bittner J, Science, August 14, 1936, 84: 2171, p 162

 

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

 

Bock M, Endogenous retroviruses and the human germline, Current Opinions in Genetics & Development, 2000, 10: 651-655

 

Chopra H, Cancer Research, 1970, 30: 8, 2081-2086

 

Callahan R, Detection and cloning of human DNA sequences related to the mouse mammary tumor virus genome, Proc Natl Acad Sci USA, 1982, 79:5503-5507

 

Dalton A, Some Ultrastructural Characteristics of a Series of Primary and Transplanted Plasma-Cell Tumors of the Mouse, JNCI, 1961, 26: 5, 1221-1266

 

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

 

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

 

Fennelly J, Co-amplification of tail-to-tail copies of MuRVY and APE retroviral genomes on the Mus musculus Y Chromosome, Mammalian Genome, 1996, 7: 31-36

 

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

 

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

 

Gray D, Activation of int-1 and int-2 Loci in GRf  Mammary Tumors, Virology, 1986, 154: 271-278

 

Griffiths D, Endogenous retroviruses in the human genome sequence, Genome Biology, 2001, 2: 6, 1017.1-1017.5

 

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

 

Holland J, Breast Cancer Res Treat, 2006, 100:Absract 6

 

Hughes J, Evidence for genomic rearrangements mediated by human endogenous retroviruses during primate evolution, Nature Genetics, 2001, 29: 487-489

 

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

 

Karlsson H Retroviral RNA identified in the cerebrospinal fluids of brains of individuals with schizophrenia, PNAS, 2001, 98: 8, 4634-4639

 

Larson E, Human Endogenous Proviruses, Current Topics in Microbiology and Immunology, 1989, 148:115-132

 

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

 

Leib C, Endogenous Retroviral Elements in Human DNA, Cancer research (Supp), 1990, 50:5636-5642

 

Links J, The Growth Accelerating Effect of Bittner Virus in Monolayers of Baby Mouse Kidney Cells, J. Gen Virol, 1969, 5:547-550

 

Lower R, A General Method for the Identification of Transcribed Retrovirus Sequences (R-U5 PCR) Reveals the Expression of the Human Endogenous Retrovirus Loci HERV-H and HERV-K in teratocarcinoma Cells, Virology, 1992, Virology, 192: 501-511

 

Lower R, The pathogenic potential of endogenous retroviruses:  facts and fantasies, Trends in Microbiology, 1999, 7: 9, 350-356

 

Mager D, HERV-H Endogenous Retroviruses:  Presence in the New World Branch but Amplification in the Old World Primate Lineage, Virology, 1995, 213: 395-404

 

Mager D, Novel Mouse Type D Endogenous Proviruses and ETn Elements Share Long Terminal Repeat and Internal Sequences, J Virology, 2000, 74: 16, 7221-7229

 

Marchetti A, Host Genetic Background Effect o the Frequency of Mouse Mammary Tumor Virus-Induced Rearrangements of the int-1 and int-2 Loci in Mouse Mammary Tumors, J Virology, 1991, 65: 8, 4550-4554

 

Marrack P, A maternally inherited superantigen encoded by a mammary tumour virus, Nature, 1991, 349:524-525

 

McGrath C, J Virology, 1972, 9: 2, 367-376

 

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