Abstract
The three viruses most studied as possible causes of human breast cancer are mouse mammary tumor virus-like sequences (MMTV-LS), Epstein-Barr virus (EBV), and oncogenic (high risk) types of human papilloma virus (HPV). The first step in fulfilling traditional criteria for inferring that a cancer is caused by a virus is to demonstrate the virus in the affected tissue. Molecular techniques, compared to host antibody assessment and immunohistochemistry, are the most definitive in establishing viral presence. Results of 85 original molecular research investigations to detect one or more of the three viruses have been extremely divergent with no consensus reached. We evaluated the methodology of these studies for the following: type of molecular assay, DNA/RNA quality control, positive and negative assay controls, type of fixation, genome targets, methods for preventing and detecting molecular contamination, pathology of specimens processed, sample size, and proportion of specimens positive for the viral genome region targeted. Only seven of the studies convincingly demonstrated the presence of an oncogenic virus biomarker (EBV: 4/30 studies (13%); HPV 3/29 studies (10%), whereas 25 convincingly demonstrated absence of the virus studied (MMTV-LS: 4/25 (16%); EBV: 15/30 (50%); 6/29 (21%). The remainder of the studies suffered shortcomings, which, in our opinion, prevented a definitive conclusion. Only one of the studies compared frequency of the virus in breast tissue of breast cancer patients versus appropriate normal control subjects with no history of breast cancer. None of the studies were designed as epidemiologic studies to determine if the presence of the virus was significantly associated with breast cancer. Based on our evaluation, the data in the publications reviewed here remain preliminary, and do not justify a conclusion that MMTV-LS, HPV, or EBV are causally associated with breast cancer. However, they form a valuable basis for redirecting future studies.
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References
Dumitrescu RG, Cotarla I (2005) Understanding breast cancer risk—Where do we stand in 2005? J Cell Mol Med 9:208–221
Collaborative Group on Hormonal Factors in Breast Cancer (2005) Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease. Lancet 358:1389–1399
Bittner JJ (1943) Possible relationships of oestrogenic hormones, genetic susceptibility, and milk influence in the production of mammary cancer in mice. Cancer Res 2:710–721
Butel JS (2000) Viral carcinogenesis: revelation of molecular mechanisms and etiology of human disease. Carcinogenesis 21:405–426
Moore PS, Chang Y (2010) Why do viruses cause cancer? Highlights of the first century of human tumor virology. Nat Rev Cancer 10:878–889
Mant C, Hodgson S, Hobday R, D’Arrigo C, Cason J (2004) A viral aetiology for breast cancer: time to re-examine the postulate. Intervirology 47:2–13
Robert-Guroff M, Buehring GC (2000) In pursuit of a human breast cancer virus, from mouse to human. In: Goedert JJ (ed) Infectious causes of cancer: targets for intervention. Humana Press, Totowa, pp 475–487
Szabo S, Haislip AM, Garry RF (2005) Of mice, cats, and men: Is human breast cancer a zoonosis? Microsc Res Tech 68:197–208
Mant C, Cason J (2004) A human murine mammary tumour virus-like agent is an unconvincing aetiological agent for human breast cancer. Rev Med Virol 14:169–177
May FE, Westley BR, Rochefort H, Buetti E, Diggelmann H (1983) Mouse mammary tumour virus related sequences are present in human DNA. Nucleic Acids Res 11:4127–4139
de Parseval N, Heidmann T (2005) Human endogenous retroviruses: from infectious elements to human genes. Cytogenet Genome Res 110:318–332
Wang Y, Holland JF, Bleiweiss IJ, Melana S, Liu X, Pelisson I, Cantarella A, Stellrecht K, Mani S, Pogo BG (1995) Detection of mammary tumor virus env gene-like sequences in human breast cancer. Cancer Res 55:5173–5179
Beaulieu BL, Sullivan JL (2002) Epstein-Barr virus. In: Richmann DD, Whitley RJ, Hayden FG (eds) Clinical virology, 2nd edn. ASM Press, Washington, p 483
Higgins CD, Swerdlow AJ, Macsween KF, Harrison N, Williams H, McAulay K, Thomas R, Reid S, Conacher M, Britton K et al (2007) A study of risk factors for acquisition of Epstein-Barr virus and its subtypes. J Infect Dis 195:474–482
Labrecque LG, Barnes DM, Fentiman IS, Griffin BE (1995) Epstein-Barr virus in epithelial cell tumors: a breast cancer study. Cancer Res 55:39–45
Sasco AJ, Lowenfels AB, Pasker-de Jong P (1993) Review article: epidemiology of male breast cancer. A meta-analysis of published case-control studies and discussion of selected aetiological factors. Int J Cancer 53:538–549
Abhyankar SH, Chiang KY, McGuirk JP, Pati AR, Godder KT, Welsh JA, Waldron RL, McElveen JL, Henslee-Downey PJ (1998) Late onset Epstein-Barr virus-associated lymphoproliferative disease after allogeneic bone marrow transplant presenting as breast masses. Bone Marrow Transplant 21:295–297
Lespagnard L, Cochaux P, Larsimont D, Degeyter M, Velu T, Heimann R (1995) 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 103:449–452
Bonnez W (2002) Papillomavirus. In: Richmann DD, Whitley RJ, Hayden FG (eds) Clinical virology, 2nd edn. ASM Press, Washington, p 583
Hobbs CGL, Sterne JAC, Bailey M, Heyderman RS, Birchall MA, Thomas SJ (2006) Human papillomavirus and head and neck caner: a systematic review and meta-analysis. Clin Otolaryngol 31:259–266
Band V, Zajchowski D, Kulesa V, Sager R (1990) Human papilloma virus DNAs immortalize normal human mammary epithelial cells and reduce their growth factor requirements. Proc Natl Acad Sci USA 87:463–467
Lawson JS, Gunzburg WH, Whitaker NJ (2006) Viruses and human breast cancer. Future Microbiol 1:33–51
Lawson JS, Tran D, Rawlinson WD (2001) From Bittner to Barr: a viral, diet, and hormone breast cancer aetiology hypothesis. Breast Cancer Res 3:81–85
Brower V (2009) Mouse mammary tumor virus: New tumor virus or just a rumor virus? J Natl Cancer Inst 101:293–295
Hill AB (1965) The environment and disease: Association or causation? Proc R Soc Med 58:295–300
Evans AS, Mueller NE (1990) Viruses and cancer. Causal associations. Ann Epidemiol 1:71–92
Susser M (1991) What is a cause, how do we know one? A grammar for pragmatic epidemiology. Am J Epidemiol 133:635–648
Pogo BG, Melana SM, Holland JF, Mandeli JF, Pilotti S, Casalini P, Menard S (1999) Sequences homologous to the mouse mammary tumor virus env gene in human breast carcinoma correlate with overexpression of laminin receptor. Clin Cancer Res 5:2108–2111
Etkind P, Du J, Khan A, Pillitteri J, Wiernik PH (2000) Mouse mammary tumor virus-like ENV gene sequences in human breast tumors and in a lymphoma of a breast cancer patient. Clin Cancer Res 6:1273–1278
Wang Y, Pelisson I, Melana SM, Go V, Holland JF, Pogo BG (2001) MMTV-like env gene sequences in human breast cancer. Arch Virol 146:171–180
Melana SM, Holland JF, Pogo BG (2001) Search for mouse mammary tumor virus-like env sequences in cancer and normal breast from the same individuals. Clin Cancer Res 7:283–284
Wang Y, Pelisson I, Melana SM, Holland JF, Pogo BG (2001) Detection of MMTV-like LTR and LTR-env gene sequences in human breast cancer. Int J Oncol 18:1041–1044
Zangen R, Harden S, Cohen D, Parrella P, Sidransky D (2002) Mouse mammary tumor-like env gene as a molecular marker for breast cancer? Int J Cancer 102:304–307
Ford CE, Tran D, Deng Y, Ta VT, Rawlinson WD, Lawson JS (2003) Mouse mammary tumor virus-like gene sequences in breast tumors of Australian and Vietnamese women. Clin Cancer Res 9:1118–1120
Wang Y, Melana SM, Baker B, Bleiweiss I, Fernandez-Cobo M, Mandeli JF, Holland JF, Pogo BG (2003) High prevalence of MMTV-like env gene sequences in gestational breast cancer. Med Oncol 20:233–236
Witt A, Hartmann B, Marton E, Zeillinger R, Schreiber M, Kubista E (2003) The mouse mammary tumor virus-like env gene sequence is not detectable in breast cancer tissue of Austrian patients. Oncol Rep 10:1025–1029
Ford CE, Faedo M, Crouch R, Lawson JS, Rawlinson WD (2004) Progression from normal breast pathology to breast cancer is associated with increasing prevalence of mouse mammary tumor virus-like sequences in men and women. Cancer Res 64:4755–4759
Lawson JS, Tran DD, Ford C, Rawlinson WD (2004) Elevated expression of the tumor suppressing protein p53 is associated with the presence of mouse mammary tumor-like env gene sequences (MMTV-like) in human breast cancer. Breast Cancer Res Treat 87:13–17
Mant C, Gillett C, D’Arrigo C, Cason J (2004) Human murine mammary tumour virus-like agents are genetically distinct from endogenous retroviruses and are not detectable in breast cancer cell lines or biopsies. Virology 318:393–404
Faedo M, Ford CE, Mehta R, Blazek K, Rawlinson WD (2004) Mouse mammary tumor-like virus is associated with p53 nuclear accumulation and progesterone receptor positivity but not estrogen positivity in human female breast cancer. Clin Cancer Res 10:4417–4419
Levine PH, Pogo BG, Klouj A, Coronel S, Woodson K, Melana SM, Mourali N, Holland JF (2004) Increasing evidence for a human breast carcinoma virus with geographic differences. Cancer 101:721–726
Etkind PR, Stewart AFR, Dorai T, Purcell DJ, Wiernik PH (2004) 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 10:5656–5664
Ford CE, Faedo M, Rawlinson WD (2004) Mouse mammary tumor virus-like RNA transcripts and DNA are found in affected cells of human breast cancer. Clin Cancer Res 10:7284–7289
Zammarchi F, Pistello M, Piersigilli A, Murr R, Di Cristofano C, Naccarato AG, Bevilacqua G (2006) MMTV-like sequences in human breast cancer: a fluorescent PCR/laser microdissection approach. J Pathol 209:436–444
Lawson JS, Tran DD, Carpenter E, Ford CE, Rawlinson WD, Whitaker NJ, Delprado W (2006) Presence of mouse mammary tumour-like virus gene sequences may be associated with morphology of specific human breast cancer. J Pathol 59:1287–1292
Bindra A, Muradrasoli S, Kisekka R, Nordgren H, Warnberg F, Blomberg J (2007) Search for DNA of exogenous mouse mammary tumor virus-related virus in human breast cancer samples. J Gen Virol 88:1806–1809
Zapata-Benavides P, Saavedra-Alonso S, Zamora-Avila D, Vargas-Rodarte C, Barrera-Rodríguez R, Salinas-Silva J, Rodríguez-Padilla C, Tamez-Guerra R, Trejo-Avila L (2007) Mouse mammary tumor virus-like gene sequences in breast cancer samples of Mexican women. Intervirology 50:402–407
Mok MTS, Lawson JS, Lacopetta BJ, Whitaker NJ (2008) Mouse mammary tumor virus-like env sequences in human breast cancer. Int J Cancer 122:2864–2870
Fukuoka H, Moriuchi M, Yano H, Nagayasu T, Moriuchi H (2008) No association of mouse mammary tumor virus-related retrovirus with Japanese cases of breast cancer. J Med Virol 80:1447–1451
Hachana M, Trimeche M, Ziadi S, Amara K, Gaddas N, Mokni M, Korbi S (2008) Prevalence and characteristics of the MMTV-like associated breast carcinomas in Tunisia. Cancer Lett 271:222–230
Park DJ, Southey MC, Giles GG, Hopeer JL (2011) No evidence of MMTV-like env sequences in specimens from the Australian Breast Cancer Family Study. Breast Cancer Res Treat 125:229–235
Gaffey MJ, Frierson HF Jr, Mills SE, Boyd JC, Zarbo RJ, Simpson JF, Gross LK, Weiss LM (1993) Medullary carcinoma of the breast. Identification of lymphocyte subpopulations and their significance. Mod Pathol 6:721–728
Horiuchi K, Mishima K, Ohsawa M, Aozasa K (1994) Carcinoma of stomach and breast with lymphoid stroma: localisation of Epstein-Barr virus. J Clin Pathol 47:538–540
Luqmani YA, Shousha S (1995) Presence of Epstein-Barr virus in breast carcinoma. Int J Oncol 6:899–903
Chu JS, Chen CC, Chang KJ (1998) In situ detection of Epstein-Barr virus in breast cancer. Cancer Lett 124:53–57
Glaser SL, Ambinder RF, DiGiuseppe JA, Horn-Ross PL, Hsu JL (1998) Absence of Epstein-Barr virus EBER-1 transcripts in an epidemiologically diverse group of breast cancers. Int J Cancer 75:555–558
Bonnet M, Guinebretiere JM, Kremmer E, Grunewald V, Benhamou E, Contesso G, Joab I (1999) Detection of Epstein-Barr virus in invasive breast cancers. J Natl Cancer Inst 91:1376–1381
Brink AA, van Den Brule AJ, van Diest P, Meijer CJ (2000) Re: detection of Epstein-Barr virus in invasive breast cancers. J Natl Cancer Inst 92:655–656 author reply 656
Dadmanesh F, Peterse JL, Sapino A, Fonelli A, Eusebi V (2001) Lymphoepithelioma-like carcinoma of the breast: lack of evidence of Epstein-Barr virus infection. Histopathology 38:54–61
McCall SA, Lichy JH, Bijwaard KE, Aguilera NS, Chu WS, Taubenberger JK (2001) Epstein-Barr virus detection in ductal carcinoma of the breast. J Natl Cancer Inst 93:148–150
Fina F, Romain S, Ouafik L, Palmari J, Ben Ayed F, Benharkat S, Bonnier P, Spyratos F, Foekens JA, Rose C et al (2001) Frequency and genome load of Epstein-Barr virus in 509 breast cancers from different geographical areas. Br J Cancer 84:783–790
Chu PG, Chang KL, Chen YY, Chen WG, Weiss LM (2001) No significant association of Epstein-Barr virus infection with invasive breast carcinoma. Am J Pathol 159:571–578
Kijima Y, Hokita S, Takao S, Baba M, Natsugoe S, Yoshinaka H, Aridome K, Otsuji T, Itoh T, Tokunaga M et al (2001) Epstein-Barr virus involvement is mainly restricted to lymphoepithelial type of gastric carcinoma among various epithelial neoplasms. J Med Virol 64:513–518
Deshpande CG, Badve S, Kidwai N, Longnecker R (2002) Lack of expression of the Epstein-Barr virus (EBV) gene products, EBERs, EBNA1, LMP1, and LMP2A, in breast cancer cells. Lab Invest 82:1193–1199
Grinstein S, Preciado MV, Gattuso P, Chabay PA, Warren WH, De Matteo E, Gould VE (2002) Demonstration of Epstein-Barr virus in carcinomas of various sites. Cancer Res 2002(62):4876–4878
Herrmann K, Niedobitek G (2003) Lack of evidence for an association of Epstein-Barr virus infection with breast carcinoma. Breast Cancer Res 5:R13–R17
Murray PG, Lissauer D, Junying J, Davies G, Moore S, Bell A, Timms J, Rowlands D, McConkey C, Reynolds GM et al (2003) Reactivity with A monoclonal antibody to Epstein-Barr virus (EBV) nuclear antigen 1 defines a subset of aggressive breast cancers in the absence of the EBV genome. Cancer Res 63:2338–2343
Xue SA, Lampert IA, Haldane JS, Bridger JE, Griffin BE (2003) Epstein-Barr virus gene expression in human breast cancer: protagonist or passenger? Br J Cancer 89:113–119
Huang J, Chen H, Hutt-Fletcher L, Ambinder RF, Hayward SD (2003) Lytic viral replication as a contributor to the detection of Epstein-Barr virus in breast cancer. J Virol 77:13267–13274
Tsai JH, Tsai CH, Cheng MH, Lin SJ, Xu FL, Yang CC (2005) Association of viral factors with non-familial breast cancer in Taiwan by comparison with non-cancerous, fibroadenoma, and thyroid tumor tissues. J Med Virol 75:276–281
Preciado MV, Chabay PA, De Matteo EN, Gonzalez P, Grinstein S, Actis A, Gass HD (2005) Epstein-Barr virus in breast carcinoma in Argentina. Arch Pathol Lab Med 129:377–381
Thorne LB, Ryan JL, Elmore SH, Glaser SL, Gulley ML (2005) Real-time PCR measures Epstein-Barr virus DNA in archival breast adenocarcinomas. Diagn Mol Pathol 14:29–33
Perrigoue JG, den Boon JA, Friedl A, Newton MA, Ahlquist P, Sugden B (2005) Lack of association between EBV and breast carcinoma. Cancer Epidemiol Biomarkers Prev 14:809–814
Kalkan A, Ozdarendeli A, Bulut Y, Yekeler H, Cobanoglu B, Doymaz MZ (2005) Investigation of Epstein-Barr virus DNA in formalin-fixed and paraffin-embedded breast cancer tissues. Med Princ Pract 14:268–271
Arbach H, Viglasky V, Lefeu F, Guinebretiere JM, Ramirez V, Bride N, Boualaga N, Bauchet T, Peyrat JP, Mathieu MC et al (2006) Epstein-Barr virus (EBV) genome and expression in breast cancer tissue: effect of EBV infection of breast cancer cells on resistance to paclitaxel (Taxol). J Virol 80:845–853
Perkins RS, Sahm K, Marando C, Dickson-Witmer D, Pahnke GR, Mitchell M, Petrelli NJ (2006) Analysis of Epstein-Barr virus reservoirs in paired blood and breast cancer primary biopsy specimens by real time PCR. Breast Cancer Res 8:R70
Fawzy S, Sallam M, Awad NM (2008) Detection of Epstein-Barr virus in breast carcinoma in Egyptian women. Clin Biochem 41:486–492
Mazouni C, Fina F, Romain S, Ouafik L, Bonnier P, Brandone J-M, Martin P-M (2011) Epstein-Barr virus as a marker of biological aggressiveness in breast cancer. Br J Cancer 104:332–337
Kadivar M, Monabati A, Joulaee A, Hosseini N (2011) Epstein-Barr virus and breast cancer: lack of evidence for an association in Iranian Women. Pathol Oncol Res, January 6, 2011. Epub ahead of print
Di Lonardo A, Venuti A, Marcante ML (1992) Human papillomavirus in breast cancer. Breast Cancer Res Treat 21:95–100
Bratthauer GL, Tavassoli FA, O’Leary TJ (1992) Etiology of breast carcinoma: no apparent role for papillomavirus types 6/11/16/18. Pathol Res Pract 188:384–386
Wrede D, Luqmani YA, Coombes RC, Vousden KH (1992) Absence of HPV 16 and 18 DNA in breast cancer. Br J Cancer 65:891–894
Czerwenka K, Heuss F, Hosmann JW, Manavi M, Lu Y, Jelincic D, Kubista E (1996) Human papilloma virus DNA: A factor in the pathogenesis of mammary Paget’s disease? Breast Cancer Res Treat 41:51–57
Gopalkrishna V, Singh UR, Sodhani P, Sharma JK, Hedau ST, Mandal AK, Das BC (1996) Absence of human papillomavirus DNA in breast cancer as revealed by polymerase chain reaction. Breast Cancer Res Treat 39:197–202
Hennig EM, Suo Z, Thoresen S, Holm R, Kvinnsland S, Nesland JM (1999) Human papillomavirus 16 in breast cancer of women treated for high grade cervical intraepithelial neoplasia (CIN III). Breast Cancer Res Treat 53:121–135
Yu Y, Morimoto T, Sasa M, Okazaki K, Harada Y, Fujiwara T, Irie Y, Takahashi E, Tanigami A, Izumi K (1999) HPV33 DNA in premalignant and malignant breast lesions in Chinese and Japanese populations. Anticancer Res 19:5057–5061
Yu Y, Morimoto T, Sasa M, Okazaki K, Harada Y, Fujiwara T, Irie Y, Takahashi E, Tanigami A, Izumi K (2000) Human papillomavirus type 33 DNA in breast cancer in Chinese. Breast Cancer 7:33–36
Liu Y, Klimberg VS, Andrews NR, Hicks CR, Peng H, Chiriva-Internati M, Henry-Tillman R, Hermonat PL (2001) Human papillomavirus DNA is present in a subset of unselected breast cancers. J Hum Virol 4:329–334
Li T, Lu ZM, Guo M, Wu QJ, Chen KN, Xing HP, Mei Q, Ke Y (2002) p53 codon 72 polymorphism (C/G) and the risk of human papillomavirus-associated carcinomas in China. Cancer 95:2571–2576
Damin AP, Karam R, Zettler CG, Caleffi M, Alexandre CO (2004) Evidence for an association of human papillomavirus and breast carcinomas. Breast Cancer Res Treat 84:131–137
Widschwendter A, Brunhuber T, Wiedemair A, Mueller-Holzner E, Marth C (2004) Detection of human papillomavirus DNA in breast cancer of patients with cervical cancer history. J Clin Virol 31:292–297
de Villiers EM, Sandstrom RE, zur Hausen H, Buck CE (2005) Presence of papillomavirus sequences in condylomatous lesions of the mamillae and in invasive carcinoma of the breast. Breast Cancer Res 7:R1–R11
Kan CY, Iacopetta BJ, Lawson JS, Whitaker NJ (2005) Identification of human papillomavirus DNA gene sequences in human breast cancer. Br J Cancer 93:946–948
Kroupis C, Markou A, Vourlidis N, Dionyssiou-Asteriou N, Lianidou ES (2006) Presence of high-risk human papillomavirus sequences in breast cancer tissues and association with histopathological characteristics. Clin Biochem 39:727–731
Gumus M, Yumuk PF, Salepci T, Aliustaoglu M, Dane F, Ekenel M, Basaran G, Kaya H, Barisik N, Turhal NS (2006) HPV DNA frequency and subset analysis in human breast cancer patients’ normal and tumoral tissue samples. J Exp Clin Cancer Res 25:515–521
Choi YL, Cho EY, Kim JH, Nam SJ, Oh YL, Song SY, Yang JH, Kim DS (2007) Detection of human papillomavirus DNA by DNA chip in breast carcinomas of Korean women. Tumor Biol 28:327–332
Lindel K, Forster A, Altermatt HJ, Greiner R, Gruber G (2007) Breast cancer and human papillomavirus (HPV) infection: no evidence of a viral etiology in a group of Swiss women. The Breast 16:172–177
Akil N, Yasmeen A, Kassab A, Ghabreau L, Darnel AD, Al Moustafa A-E (2008) High-risk human papillomavirus infections in breast cancer in Syrian women and their association with Id-I expression: a tissue microarray study. Br J Cancer 99:404–407
de Cremoux P, Thioux M, Lebigot I, Sigal-Zafrani B, Salmon R, Sastre-Garau X (2008) No evidence of human papillomavirus DNA sequences in invasive breast carcinoma. Breast Cancer Res 109:55–58
Khan NA, Castillo A, Koriyama C, Kijima Y, Umekita Y, Ohi Y, Higashi M, Sagara Y, Yoshinaka H, Tsuji T et al (2008) Human papillomavirus detected in female breast carcinomas in Japan. Br J Cancer 99:408–414
De Leon DC, Montiel DP, Nemcova J, Mykyskova I, Turcios E, Villavicencio V, Cetina L, Coronel A, Hes O (2009) Human Papillomavirus (HPV) in breast tumors: prevalence in a group of Mexican patients. BMC Cancer 9:26
Mendizabul-Ruiz AP, Morales EJA, Rami’rez-Jirano LJ, Padilla-Rosa EM, Mora’n-Moguel MC, Montoya-Fuentes EH (2009) Low frequency of human papillomavirus DNA in breast cancer tissue. Breast Cancer Res 114:189–194
Heng B, Glenn WK, Ye Y, Tran B, Delprado W, Lutze-Mann L, Whitaker NJ, Lawson JS (2009) Human papilloma virus is associated with breast cancer. Br J Cancer 101:1345–1350
Hachana M, Ziadi S, Amara K, Toumi I, Korbi S, Trimeche M (2010) No evidence of human papillomavirus DNA in breast carcinoma in Tunisian patients. The Breast 19:541–544
Hedau S, Kumar U, Hussain S, Shukla S, Pande S, Jain N et al (2011) Breast cancer and human papillomavirus infection: no evidence of HPV etiology of breast cancer in Indian women. BMC Cancer 11:27–37
Silva RG, da Silva BB (2011) No evidence for an association of human papillomavirus and breast carcinoma. Breast Cancer Res Treat 125:261–264
Baltzell K, Buehring GC, Krishnamurthy S, Kuerer H, Shen HM, Sison JD (2011) Limited evidence of human papillomavirus in breast tissue using molecular in situ methods. Cancer. doi:10.1002/cncr.26389
Liu B, Wang Y, Melana SM, Pelisson I, Najfeld V, Holland JF, Pogo BG (2011) Identification of a proviral structure in human breast cancer. Cancer Res 61:1754–1759
Wang Y, Go V, Holland JF, Melana SM, Pogo BG (1998) Expression of mouse mammary tumor virus-like env gene sequences in human breast cancer. Clin Cancer Res 4:2565–2568
Resnick RM, Cornelissen MTE, Wright DK, Eichinger GH, Fox HS, Schegget JT, Manos MM (1990) Detection and typing of human papillomavirus in archival cervical cancer specimens by DNA. J Natl Cancer Inst 82:148–1477
Smits HL, Tieben LM, Tjong AHSP, Jebbink MF, Minnaar RP, Jansen CL, ter Schegget J (1992) Detection and typing of human papillomaviruses present in fixed and stained archival cervical smears by a consensus polymerase chain reaction and direct sequence analysis allow the identification of a broad spectrum of human papillomavirus types. J Gen Virol 73:3263–3268
Gillio-Tos A, De Marco L, Fiano V, Garcia-Bragado F, Dikshit R, Boffetta P, Merletti F (2007) Efficient DNA extraction from 25-year-old paraffin-embedded tissues: study of 365 samples. Pathology 39:345–348
Kadin ME, Vonderheid EC, Weiss LM (1993) Absence of Epstein-Barr viral RNA in lymphomatoidpapulosis. J Pathol 170:145–148
Morris B (2005) Cervical human papillomavirus screening by PCR: advantages of targeting the E6/E7 region. Clin Chem Lab Med 43:1171–1177
Glaser SL, Hsu JL, Gulley ML (2004) Epstein-Barr virus and breast cancer: state of the evidence for viral carcinogenesis. Cancer Epidemiol Biomarkers Prev 13:688–697
Longworth MS, Laimins LA (2004) Pathogenesis of human papillomaviruses in differentiating epithelia. Microbiol Molec Biol Rev 68:362–372
Fitzgibbons PL, Henson DE, Hutter RVP (1998) Benign breast changes and the risk for subsequent breast cancer: an update of the 1985 consensus statement. Arch Pathol Lab Med 122:1053–1055
Chu TY, Shen SY, Lee HS, Liu HS (1999) Monoclonality and surface lesion-specific microsatellite alterations in premalignant and malignant neoplasia of uterine cervi: a local field effect of genomic instability and clonal evolution. Genes Chromosome Cancer 24:127–134
Slaughter DP, Southwick HW, Smejkal W (1953) Field cancerization in oral stratified squamous epithelium: clinical implications of multicentric origin. Cancer 6:963–968
Heaphy CM, Griffith JK, Bisoffi M (2009) Molecular field cancerization: molecular evidence and clinical importance. Breast Cancer Res Treat 118:229–239
Dryden J (1972) All for Love. In: Vieth DM (ed) Regents restoration drama series. University of Nebraska Press, Lincoln, NE, prologue, lines 13–14
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We thank Diana Jin and David Chu for help in manuscript preparation.
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Joshi, D., Buehring, G.C. Are viruses associated with human breast cancer? Scrutinizing the molecular evidence. Breast Cancer Res Treat 135, 1–15 (2012). https://doi.org/10.1007/s10549-011-1921-4
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DOI: https://doi.org/10.1007/s10549-011-1921-4