Mammakarzinom und Viren

Zusammenfassung

Auf der Suche nach neuen Therapieformen zur Behandlung des metastasierenden Mammakarzinoms stellt die Virotherapie eine Erfolg versprechende Methode dar. In der folgenden Übersicht werden das Konzept, Strategien und der gegenwärtige Stand der Virotherapie beim Mammakarzinom dargelegt. Ferner wird die virale Ätiologie des Mammakarzinoms evaluiert und diskutiert.

Abstract

In the search for new forms of therapy to treat metastasizing breast carcinoma virotherapy appears to offer some promise. In the following, the concept, strategies and current state of knowledge on virotherapy for the treatment of breast carcinoma is presented. The viral etiology of breast carcinoma is evaluated and discussed.

Mammakarzinom - Viren - Virotherapie - Gentherapie - CRAds - Adenovirus - Maus-Mamma-Tumor Virus (MMTV)

Breast carcinoma - virotherapy - gene therapy - CRAds - adenovirus - mouse-mammary-tumor virus (MMTV)

Literatur

• 1 Jemal A, Clegg L X, Ward E, Ries L A, Wu X, Jamison P M, Wingo P A, Howe H L, Anderson R N, Edwards B K. Annual report to the nation on the status of cancer, 1975 - 2001, with a special feature regarding survival.  Cancer. 2004;  101 3-27
• 2 Bilbao R, Bustos M, Alzuguren P, Pajares M J, Drozdzik M, Qian C, Prieto J. A blood-tumor barrier limits gene transfer to experimental liver cancer: The effect of vasoactive compounds.  Gene Ther. 2000;  7 1824-1832
• 3 Stoff-Khalili M A, Dall P, Curiel D T. From gene therapy to virotherapy for ovarian cancer.  Minerva Ginecol. 2004;  56 503-514
• 4 Alemany R, Balague C, Curiel D T. Replicative adenoviruses for cancer therapy.  Nat Biotechnol. 2000;  18 723-727
• 5 Nettelbeck D M. Virotherapeutics: Conditionally replicative adenoviruses for viral oncolysis.  Anticancer Drugs. 2003;  14 577-584
• 6 Kruyt F A, Curiel D T. Toward a new generation of conditionally replicating adenoviruses: Pairing tumor selectivity with maximal oncolysis.  Hum Gene Ther. 2002;  13 485-495
• 7 Bauerschmitz G J, Hemminki A, Curiel D T, Dall P. Tumour-dependent replicating adenoviruses in the treatment of carcinomas.  Zentralbl Gynakol. 2004;  126 280-281
• 8 Kirn D, Martuza R L, Zwiebel J. Replication-selective virotherapy for cancer: Biological principles, risk management and future directions.  Nat Med. 2001;  7 781-787
• 9 Kirn D. Replication-selective oncolytic adenoviruses: Virotherapy aimed at genetic targets in cancer.  Oncogene. 2000;  19 6660-6669
• 10 Yang W Q, Senger D L, Lun X Q, Muzik H, Shi Z Q, Dyck R H, Norman K, Brasher P M, Rewcastle N B, George D, Stewart D, Lee P W, Forsyth P A. Reovirus as an experimental therapeutic for brain and leptomeningeal metastases from breast cancer.  Gene Ther. 2004;  11 1579-1589
• 11 Norman K L, Coffey M C, Hirasawa K, Demetrick D J, Nishikawa S G, DiFrancesco L M, Strong J E, Lee P W. Reovirus oncolysis of human breast cancer.  Hum Gene Ther. 2002;  13 641-652
• 12 Ebert O, Harbaran S, Shinozaki K, Woo S L. Systemic therapy of experimental breast cancer metastases by mutant vesicular stomatitis virus in immune-competent mice.  Cancer Gene Ther. 2005;  12 350-358
• 13 Stojdl D F, Lichty B, Knowles S, Marius R, Atkins H, Sonenberg N, Bell J C. Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus.  Nat Med. 2000;  6 821-825
• 14 Mundschau L J, Faller D V. Endogenous inhibitors of the dsRNA-dependent eIF‐2 alpha protein kinase PKR in normal and ras-transformed cells.  Biochimie. 1994;  76 792-800
• 15 Stojdl D F, Lichty B D, tenOever B R, Paterson J M, Power A T, Knowles S, Marius R, Reynard J, Poliquin L, Atkins H, Brown E G, Durbin R K, Durbin J E, Hiscott J, Bell J C. VSV strains with defects in their ability to shutdown innate immunity are potent systemic anti-cancer agents.  Cancer Cell. 2003;  4 263-275
• 16 Fabra A, Parada C, Vinyals A, Martin Duque P, Fernandez V, Sanchez-Prieto R, Ramon y Cajal S. Intravascular injections of a conditional replicative adenovirus (adl118) prevent metastatic disease in human breast carcinoma xenografts.  Gene Ther. 2001;  8 1627-1634
• 17 Coukos G, Makrigiannakis A, Kang E H, Rubin S C, Albelda S M, Molnar-Kimber K L. Oncolytic herpes simplex virus-1 lacking ICP34.5 induces p 53-independent death and is efficacious against chemotherapy-resistant ovarian cancer.  Clin Cancer Res. 2000;  6 3342-3353
• 18 Todo T, Martuza R L, Rabkin S D, Johnson P A. Oncolytic herpes simplex virus vector with enhanced MHC class I presentation and tumor cell killing.  Proc Natl Acad Sci USA. 2001;  98 6396-6401
• 19 Liu R, Varghese S, Rabkin S D. Oncolytic herpes simplex virus vector therapy of breast cancer in C3(1)/SV40 T-antigen transgenic mice.  Cancer Res. 2005;  65 1532-1540
• 20 Liu R, Martuza R L, Rabkin S D. Intracarotid delivery of oncolytic HSV vector G47Delta to metastatic breast cancer in the brain.  Gene Ther. 2005;  12 647-654
• 21 Glasgow J N, Bauerschmitz G J, Curiel D T, Hemminki A. Transductional and transcriptional targeting of adenovirus for clinical applications.  Curr Gene Ther. 2004;  4 1-14
• 22 Hernandez-Alcoceba R, Pihalja M, Qian D, Clarke M F. New oncolytic adenoviruses with hypoxia- and estrogen receptor-regulated replication.  Hum Gene Ther. 2002;  13 1737-1750
• 23 Yu L, Yamamoto N, Kadomatsu K, Muramatsu T, Matsubara S, Sakiyama S, Tagawa M. Midkine promoter can mediate transcriptional activation of a fused suicide gene in a broader range of human breast cancer compared with c-erbB‐2 promoter.  Oncology. 2004;  66 143-149
• 24 Zhang L, Akbulut H, Tang Y, Peng X, Pizzorno G, Sapi E, Manegold S, Deisseroth A. Adenoviral vectors with E1A regulated by tumor-specific promoters are selectively cytolytic for breast cancer and melanoma.  Mol Ther. 2002;  6 386-393
• 25 Zhu Z B, Makhija S K, Lu B, Wang M, Kaliberova L, Liu B, Rivera A A, Nettelbeck D M, Mahasreshti P J, Leath C A, Barker S, Yamaoto M, Li F, Alvarez R D, Curiel D T. Transcriptional targeting of tumors with a novel tumor-specific survivin promoter.  Cancer Gene Ther. 2004;  11 256-262
• 26 Akbulut H, Zhang L, Tang Y, Deisseroth A. Cytotoxic effect of replication-competent adenoviral vectors carrying L-plastin promoter regulated E1A and cytosine deaminase genes in cancers of the breast, ovary and colon.  Cancer Gene Ther. 2003;  10 388-395
• 27 Godbey W T, Atala A. Directed apoptosis in Cox-2-overexpressing cancer cells through expression-targeted gene delivery.  Gene Ther. 2003;  10 1519-1527
• 28 Lu B, Makhija S K, Nettelbeck D M, Rivera A A, Wang M, Komarova S, Zhou F, Yamamoto M, Haisma H J, Alvarez R D, Curiel D T, Zhu Z B. Evaluation of tumor-specific promoter activities in melanoma.  Gene Ther. 2005;  12 330-338
• 29 McLaughlin P M, Trzpis M, Kroesen B J, Helfrich W, Terpstra P, Dokter W H, Ruiters M H, de Leij L F, Harmsen M C. Use of the EGP‐2/Ep-CAM promoter for targeted expression of heterologous genes in carcinoma derived cell lines.  Cancer Gene Ther. 2004;  11 603-612
• 30 McLaughlin P M, Harmsen M C, Dokter W H, Kroesen B J, van der Molen H, Brinker M G, Hollema H, Ruiters M H, Buys C H, de Leij L F. The epithelial glycoprotein 2 (EGP‐2) promoter-driven epithelial-specific expression of EGP‐2 in transgenic mice: A new model to study carcinoma-directed immunotherapy.  Cancer Res. 2001;  61 4105-4111
• 31 Zabner J, Freimuth P, Puga A, Fabrega A, Welsh M J. Lack of high affinity fiber receptor activity explains the resistance of ciliated airway epithelia to adenovirus infection.  J Clin Invest. 1997;  100 1144-1149
• 32 Okegawa T, Li Y, Pong R C, Bergelson J M, Zhou J, Hsieh J T. The dual impact of coxsackie and adenovirus receptor expression on human prostate cancer gene therapy.  Cancer Res. 2000;  60 5031-5036
• 33 Shayakhmetov D M, Li Z Y, Ni S, Lieber A. Targeting of adenovirus vectors to tumor cells does not enable efficient transduction of breast cancer metastases.  Cancer Res. 2002;  62 1063-1068
• 34 Li Y, Pong R C, Bergelson J M, Hall M C, Sagalowsky A I, Tseng C P, Wang Z, Hsieh J T. Loss of adenoviral receptor expression in human bladder cancer cells: A potential impact on the efficacy of gene therapy.  Cancer Res. 1999;  59 325-330
• 35 Seidman M A, Hogan S M, Wendland R L, Worgall S, Crystal R G, Leopold P L. Variation in adenovirus receptor expression and adenovirus vector-mediated transgene expression at defined stages of the cell cycle.  Mol Ther. 2001;  4 13-21
• 36 Okegawa T, Pong R C, Li Y, Bergelson J M, Sagalowsky A I, Hsieh J T. The mechanism of the growth-inhibitory effect of coxsackie and adenovirus receptor (CAR) on human bladder cancer: A functional analysis of car protein structure.  Cancer Res. 2001;  61 6592-6600
• 37 Walters R W, Freimuth P, Moninger T O, Ganske I, Zabner J, Welsh M J. Adenovirus fiber disrupts CAR-mediated intercellular adhesion allowing virus escape.  Cell. 2002;  110 789-799
• 38 Wu H, Seki T, Dmitriev I, Uil T, Kashentseva E, Han T, Curiel D T. Double modification of adenovirus fiber with RGD and polylysine motifs improves coxsackievirus-adenovirus receptor-independent gene transfer efficiency.  Hum Gene Ther. 2002;  13 1647-1653
• 39 Stoff-Khalili M A, Stoff A, Rivera A A, Mathis J M, Everts M, Wang M, Kawakami Y, Waehler R, Mathews Q L, Yamamoto M, Rocconi R P, Siegal G P, Richter D F, Dall P, Zhu Z B, Curiel D T. Gene Transfer to carcinoma of the breast with fiber-modified adenoviral vectors in a tissue slice model system.  Cancer Biology Therapy. 2005;  4 11
• 40 Dmitriev I, Krasnykh V, Miller C R, Wang M, Kashentseva E, Mikheeva G, Belousova N, Curiel D T. An adenovirus vector with genetically modified fibers demonstrates expanded tropism via utilization of a coxsackievirus and adenovirus receptor-independent cell entry mechanism.  J Virol. 1998;  72 9706-9713
• 41 Sirena D, Lilienfeld B, Eisenhut M, Kalin S, Boucke K, Beerli R R, Vogt L, Ruedl C, Bachmann M F, Greber U F, Hemmi S. The human membrane cofactor CD46 is a receptor for species B adenovirus serotype 3.  J Virol. 2004;  78 4454-4462
• 42 Short J J, Pereboev A V, Kawakami Y, Vasu C, Holterman M J, Curiel D T. Adenovirus serotype 3 utilizes CD80 (B7.1) and CD86 (B7.2) as cellular attachment receptors.  Virology. 2004;  322 349-359
• 43 Stoff-Khalili M A, Rivera A A, Glasgow J N, Le L P, Stoff A, Everts M, Tsuruta Y, Kawakami Y, Bauerschmitz G J, Mathis J M, Pereboeva L, Seigal G P, Dall P, Curiel D T. A human adenoviral vector with a chimeric fiber from canine adenovirus type 1 results in novel expanded tropism for cancer gene therapy.  Gene Ther. 2005;  12 1696-1706
• 44 Gromeier M, Lachmann S, Rosenfeld M R, Gutin P H, Wimmer E. Intergeneric poliovirus recombinants for the treatment of malignant glioma.  Proc Natl Acad Sci USA. 2000;  97 6803-6808
• 45 Gromeier M, Wimmer E. Viruses for the treatment of malignant glioma.  Curr Opin Mol Ther. 2001;  3 503-508
• 46 Merrill M K, Bernhardt G, Sampson J H, Wikstrand C J, Bigner D D, Gromeier M. Poliovirus receptor CD155-targeted oncolysis of glioma.  Neuro Oncol. 2004;  6 208-217
• 47 Ochiai H, Moore S A, Archer G E, Okamura T, Chewning T A, Marks J R, Sampson J H, Gromeier M. Treatment of intracerebral neoplasia and neoplastic meningitis with regional delivery of oncolytic recombinant poliovirus.  Clin Cancer Res. 2004;  10 4831-4838
• 48 Kelm J M, Timmins N E, Brown C J, Fussenegger M, Nielsen L K. Method for generation of homogeneous multicellular tumor spheroids applicable to a wide variety of cell types.  Biotechnol Bioeng. 2003;  83 173-180
• 49 Le L P, Everts M, Dmitriev I P, Davydova J G, Yamamoto M, Curiel D T. Fluorescently labeled adenovirus with pIX-EGFP for vector detection.  Mol Imaging. 2004;  3 105-116
• 50 Krumdieck C. A new instrument for the rapid preparation of tissue slices.  Anal Biochem. 1980;  104 118-123
• 51 Kirby T O, Rivera A, Rein D, Wang M, Ulasov I, Breidenbach M, Kataram M, Contreras J L, Krumdieck C, Yamamoto M, Rots M G, Haisma H J, Alvarez R D, Mahasreshti P J, Curiel D T. A novel ex vivo model system for evaluation of conditionally replicative adenoviruses therapeutic efficacy and toxicity.  Clin Cancer Res. 2004;  10 8697-8703
• 52 Bischoff J R, Kirn D H, Williams A, Heise C, Horn S, Muna M, Ng L, Nye J A, Sampson-Johannes A, Fattaey A, McCormick F. An adenovirus mutant that replicates selectively in p 53-deficient human tumor cells.  Science. 1996;  274 373-376
• 53 Vasey P A, Shulman L N, Campos S, Davis J, Gore M, Johnston S, Kirn D H, O'Neill V, Siddiqui N, Seiden M V, Kaye S B. Phase I trial of intraperitoneal injection of the E1B‐55-kd-gene-deleted adenovirus ONYX‐015 (dl1520) given on days 1 through 5 every 3 weeks in patients with recurrent/refractory epithelial ovarian cancer.  J Clin Oncol. 2002;  20 1562-1569
• 54 Reid T, Warren R, Kirn D. Intravascular adenoviral agents in cancer patients: lessons from clinical trials.  Cancer Gene Ther. 2002;  9 979-986
• 55 Reid T, Galanis E, Abbruzzese J, Sze D, Andrews J, Romel L, Hatfield M, Rubin J, Kirn D. Intra-arterial administration of a replication-selective adenovirus (dl1520) in patients with colorectal carcinoma metastatic to the liver: A phase I trial.  Gene Ther. 2001;  8 1618-1626
• 56 Nemunaitis J, Ganly I, Khuri F, Arseneau J, Kuhn J, McCarty T, Landers S, Maples P, Romel L, Randlev B, Reid T, Kaye S, Kirn D. Selective replication and oncolysis in p 53 mutant tumors with ONYX‐015, an E1B‐55 kD gene-deleted adenovirus, in patients with advanced head and neck cancer: A phase II trial.  Cancer Res. 2000;  60 6359-6366
• 57 Kirn D. Clinical research results with dl1520 (Onyx-015), a replication-selective adenovirus for the treatment of cancer: What have we learned?.  Gene Ther. 2001;  8 89-98
• 58 Reid T, Galanis E, Abbruzzese J, Sze D, Wein L M, Andrews J, Randlev B, Heise C, Uprichard M, Hatfield M, Rome L, Rubin J, Kirn D. Hepatic arterial infusion of a replication-selective oncolytic adenovirus (dl1520): phase II viral, immunologic, and clinical endpoints.  Cancer Res. 2002;  62 6070-6079
• 59 Khuri F R, Nemunaitis J, Ganly I, Arseneau J, Tannock I F, Romel L, Gore M, Ironside J, MacDougall R H, Heise C, Randlev B, Gillenwater A M, Bruso P, Kaye S B, Hong W K, Kirn D H. A controlled trial of intratumoral ONYX‐015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer.  Nat Med. 2000;  6 879-885
• 60 Wu H, Han T, Lam J T, Leath C A, Dmitriev I, Kashentseva E, Barnes M N, Alvarez R D, Curiel D T. Preclinical evaluation of a class of infectivity-enhanced adenoviral vectors in ovarian cancer gene therapy.  Gene Ther. 2004;  11 874-878
• 61 Heise C C, Williams A, Olesch J, Kirn D H. Efficacy of a replication-competent adenovirus (ONYX‐015) following intratumoral injection: Intratumoral spread and distribution effects.  Cancer Gene Ther. 1999;  6 499-504
• 62 Toda M, Rabkin S D, Martuza R L. Treatment of human breast cancer in a brain metastatic model by G207, a replication-competent multimutated herpes simplex virus 1.  Hum Gene Ther. 1998;  9 2177-2185
• 63 Herrlinger U, Kramm C M, Aboody-Guterman K S, Silver J S, Ikeda K, Johnston K M, Pechan P A, Barth R F, Finkelstein D, Chiocca E A, Louis D N, Breakefield X O. Pre-existing herpes simplex virus 1 (HSV‐1) immunity decreases, but does not abolish, gene transfer to experimental brain tumors by a HSV‐1 vector.  Gene Ther. 1998;  5 809-819
• 64 Ganly I, Kirn D, Eckhardt G, Rodriguez G I, Soutar D S, Otto R, Robertson A G, Park O, Gulley M L, Heise C, Von Hoff D D, Kaye S B. A phase I study of Onyx-015, an E1B attenuated adenovirus, administered intratumorally to patients with recurrent head and neck cancer.  Clin Cancer Res. 2000;  6 798-806
• 65 Rogulski K R, Freytag S O, Zhang K, Gilbert J D, Paielli D L, Kim J H, Heise C C, Kirn D H. In vivo antitumor activity of ONYX‐015 is influenced by p 53 status and is augmented by radiotherapy.  Cancer Res. 2000;  60 1193-1196
• 66 Breasted J. The Edwin Smith Surgical Papyrus. Chicago; University of Chicago Press 1930: 403-406
• 67 de Moulin D. Historical notes on breast cancer, with emphasis on the Netherlands; III. The growth of scientific surgery in the 19th century.  Neth J Surg. 1982;  34 193-200
• 68 Hedenfalk I, Duggan D, Chen Y, Radmacher M, Bittner M, Simon R, Meltzer P, Gusterson B, Esteller M, Kallioniemi O P, Wilfond B, Borg A, Trent J. Gene-expression profiles in hereditary breast cancer.  N Engl J Med. 2001;  344 539-548
• 69 Schmutzler C, Vogel W. An interdisciplinary approach to breast and PCA. International Symposium: Breast and PCA: Genes, Hormones and the Environment, Garmisch-Partenkirchen, Germany, 22 - 24 April 1999.  Trends Endocrinol Metab. 2000;  11 115-116
• 70 Dumitrescu R G, Cotarla I. Understanding breast cancer risk - where do we stand in 2005?.  J Cell Mol Med. 2005;  9 208-221
• 71 Hulka B S, Moorman P G. Breast cancer: Hormones and other risk factors.  Maturitas. 2001;  38 103-113 113-106 (discussion)
• 72 Levi F, Randimbison L, Te V C, La Vecchia C. Invasive breast cancer following ductal and lobular carcinoma in situ of the breast.  Int J Cancer. 2005;  116 820-823
• 73 Mc Pike H B. et al . Oral contraceptive use and early abortion risk as factors for breast cancer in young women.  Br J Cancer. 1981;  43 72-76
• 74 Henderson I C. What can a woman do about her risk of dying of breast cancer?.  Curr Probl Cancer. 1990;  14 161-230
• 75 Dupont W D, Page D L. Risk factors for breast cancer in women with proliferative breast disease.  N Engl J Med. 1985;  312 146-151
• 76 Kelsey J L, Gammon M D. The epidemiology of breast cancer.  CA Cancer J Clin. 1991;  41 146-165
• 77 Harris J R, Lippman M E, Veronesi U, Willett W. Breast cancer (1).  N Engl J Med. 1992;  327 319-328
• 78 Harris J R, Lippman M E, Veronesi U, Willett W. Breast cancer (2).  N Engl J Med. 1992;  327 390-398
• 79 Harris J R, Lippman M E, Veronesi U, Willett W. Breast cancer (3).  N Engl J Med. 1992;  327 473-480
• 80 Bodian C A. Benign breast diseases, carcinoma in situ, and breast cancer risk.  Epidemiol Rev. 1993;  15 177-187
• 81 Grady D, Rubin S M, Petitti D B, Fox C S, Black D, Ettinger B, Ernster V L, Cummings S R. Hormone therapy to prevent disease and prolong life in postmenopausal women.  Ann Intern Med. 1992;  117 1016-1037
• 82 zur Hausen H. Cervical carcinoma and human papillomavirus: On the road to preventing a major human cancer.  J Natl Cancer Inst. 2001;  93 252-253
• 83 Stuver S O, Boschi-Pinto C, Trichopoulos D. Infection with hepatitis B and C viruses, social class and cancer.  IARC Sci Publ. 1997;  138 319-324
• 84 Bangham C R. HTLV‐1 infections.  J Clin Pathol. 2000;  53 581-586
• 85 Bittner J. Some possible effects of nursing on the mammary gland tumor incidence in mice.  Science (Wash DC). 1936;  84 162
• 86 Callahan R, Smith G H. MMTV-induced mammary tumorigenesis: gene discovery, progression to malignancy and cellular pathways.  Oncogene. 2000;  19 992-1001
• 87 Kordon E C, Smith G H. An entire functional mammary gland may comprise the progeny from a single cell.  Development. 1998;  125 1921-1930
• 88 Pogo B G, Holland J F. Possibilities of a viral etiology for human breast cancer. A review.  Biol Trace Elem Res. 1997;  56 131-142
• 89 Seifarth W, Skladny H, Krieg-Schneider F, Reichert A, Hehlmann R, Leib-Mosch C. Retrovirus-like particles released from the human breast cancer cell line T47-D display type B‐and C-related endogenous retroviral sequences.  J Virol. 1995;  69 6408-6416
• 90 Dion A S, Girardi A J, Williams C C, Pomenti A A, Redfield E S. Responses of serum from breast cancer patients to murine mammary tumor virus: Fact or artifact?.  J Natl Cancer Inst. 1987;  79 207-211
• 91 Kovarik A, Hlubinova K, Prachar J, Simkovic D, Knotek J. No significant correlation between specific antibodies to mouse mammary tumour virus and human cancer.  Br J Cancer. 1989;  60 572-575
• 92 Wang Y, Holland J F, Bleiweiss I J, Melana S, Liu X, Pelisson I, Cantarella A, Stellrecht K, Mani S, Pogo B G. Detection of mammary tumor virus env gene-like sequences in human breast cancer.  Cancer Res. 1995;  55 5173-5179
• 93 Wang Y, Pelisson I, Melana S M, Holland J F, Pogo B G. Detection of MMTV-like LTR and LTR‐env gene sequences in human breast cancer.  Int J Oncol. 2001;  18 1041-1044
• 94 Wang Y, Pelisson I, Melana S M, Go V, Holland J F, Pogo B G. MMTV-like env gene sequences in human breast cancer.  Arch Virol. 2001;  146 171-180
• 95 Etkind P R, Stewart A F, Dorai T, Purcell D J, Wiernik P H. Clonal isolation of different strains of mouse mammary tumor virus-like DNA sequences from both the breast tumors and non-Hodgkin's lymphomas of individual patients diagnosed with both malignancies.  Clin Cancer Res. 2004;  10 5656-5664
• 96 Etkind P, Du J, Khan A, Pillitteri J, Wiernik P H. Mouse mammary tumor virus-like ENV gene sequences in human breast tumors and in a lymphoma of a breast cancer patient.  Clin Cancer Res. 2000;  6 1273-1278
• 97 Wang Y, Melana S M, Baker B, Bleiweiss I, Fernandez-Cobo M, Mandeli J F, Holland J F, Pogo B G. High prevalence of MMTV-like env gene sequences in gestational breast cancer.  Med Oncol. 2003;  20 233-236
• 98 Pogo B G, Melana S M, Holland J F, Mandeli J F, Pilotti S, Casalini P, Menard S. Sequences homologous to the mouse mammary tumor virus env gene in human breast carcinoma correlate with overexpression of laminin receptor.  Clin Cancer Res. 1999;  5 2108-2111
• 99 Yin H, Medstrand P, Andersson M L, Borg A, Olsson H, Blomberg J. Transcription of human endogenous retroviral sequences related to mouse mammary tumor virus in human breast and placenta: Similar pattern in most malignant and nonmalignant breast tissues.  AIDS Res Hum Retroviruses. 1997;  13 507-516
• 100 Stewart T H, Sage R D, Stewart A F, Cameron D W. Breast cancer incidence highest in the range of one species of house mouse, Mus domesticus.  Br J Cancer. 2000;  82 446-451
• 101 Melana S M, Holland J F, Pogo B G. Search for mouse mammary tumor virus-like env sequences in cancer and normal breast from the same individuals.  Clin Cancer Res. 2001;  7 283-284
• 102 Friedman L S, Ostermeyer E A, Lynch E D, Szabo C I, Meza J E, Anderson L A, Dowd P, Lee M K, Rowell S E. et al . 22 genes from chromosome 17q21: Cloning, sequencing, and characterization of mutations in breast cancer families and tumors.  Genomics. 1995;  25 256-263
• 103 Chan K H, Tam J S, Peiris J S, Seto W H, Ng M H. Epstein-Barr virus (EBV) infection in infancy.  J Clin Virol. 2001;  21 57-62
• 104 Sasco A J, Lowenfels A B, Pasker-de Jong P. Review article: Epidemiology of male breast cancer. A meta-analysis of published case-control studies and discussion of selected aetiological factors.  Int J Cancer. 1993;  53 538-549
• 105 Schouten J T, Weese J L, Carbone P P. Lymphoma of the breast.  Ann Surg. 1981;  194 749-753
• 106 Abhyankar S H, Chiang K Y, McGuirk J P, Pati A R, Godder K T, Welsh J A, Waldron R L, McElveen J L, Henslee-Downey P J. Late onset Epstein-Barr virus-associated lymphoproliferative disease after allogeneic bone marrow transplant presenting as breast masses.  Bone Marrow Transplant. 1998;  21 295-297
• 107 Yasui Y, Potter J D, Stanford J L, Rossing M A, Winget M D, Bronner M, Daling J. Breast cancer risk and “delayed” primary Epstein-Barr virus infection.  Cancer Epidemiol Biomarkers Prev. 2001;  10 9-16
• 108 Gaffey M J, Frierson Jr H F, Mills S E, Boyd J C, Zarbo R J, Simpson J F, Gross L K, Weiss L M. Medullary carcinoma of the breast. Identification of lymphocyte subpopulations and their significance.  Mod Pathol. 1993;  6 721-728
• 109 Lespagnard L, Cochaux P, Larsimont D, Degeyter M, Velu T, Heimann R. Absence of Epstein-Barr virus in medullary carcinoma of the breast as demonstrated by immunophenotyping, in situ hybridization and polymerase chain reaction.  Am J Clin Pathol. 1995;  103 449-452
• 110 Weiss R A. Viruses and human cancer. Bio Scientific Publishers 2000: 1-15
• 111 Liu B, Wang Y, Melana S M, Pelisson I, Najfeld V, Holland J F, Pogo B G. Identification of a proviral structure in human breast cancer.  Cancer Res. 2001;  61 1754-1759
• 112 Levine P H, Pogo B G, Klouj A, Coronel S, Woodson K, Melana S M, Mourali N, Holland J F. Increasing evidence for a human breast carcinoma virus with geographic differences.  Cancer. 2004;  101 721-726
• 113 Ford C E, Tran D, Deng Y, Ta V T, Rawlinson W D, Lawson J S. Mouse mammary tumor virus-like gene sequences in breast tumors of Australian and Vietnamese women.  Clin Cancer Res. 2003;  9 1118-1120
• 114 Melana S M. MMTV-like Particles in Human Breast Cancer. Cold Spring Harbor; Laboratory Annual Meeting on Retroviruses 2004: 178
• 115 Stewart T, Tsai S C, Grayson H, Henderson R, Opelz G. Incidence of de-novo breast cancer in women chronically immunosuppressed after organ transplantation.  Lancet. 1995;  346 796-798
• 116 Frisch M, Biggar R J, Engels E A, Goedert J J. Association of cancer with AIDS-related immunosuppression in adults.  Jama. 2001;  285 1736-1745
• 117 Lawson J S, Tran D, Rawlinson W D. From Bittner to Barr: A viral, diet and hormone breast cancer aetiology hypothesis.  Breast Cancer Res. 2001;  3 81-85