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A human murine mammary tumour virus‐like agent is an unconvincing aetiological agent for human breast cancer

There has recently been renewed interest in both the scientific literature, and in the media, that a human relative (HMLV) of murine mammary tumour virus (MMTV) may be implicated in the aetiology of up to 42% of sporadic cases of human breast cancer. Such reports are potentially of considerable clinical significance, as aside from the small percentage of genetically acquired breast cancers, the cause of sporadic cases of breast cancer is completely unknown. Indeed, convincing proof of an infectious cause for human breast malignancies would permit the development of new preventative measures, treatment modalities and raise the possibility of prophylactic and therapeutic vaccines. Here we review the historical background for a retroviral cause of human breast cancers and give an up‐to‐date critique of the most recent research findings. We conclude that the available evidence for an infectious aetiology of human breast cancers is unconvincing. Amongst the many cognate arguments against an infective hypothesis for sporadic cases of human breast cancer are the facts that: (i) human tissues lack the appropriate cell‐surface receptor for entry of MMTVs/HMLVs; (ii) unlike all other virally caused human malignancies, immunodeficiency does not predispose to an increased incidence, or prevalence, of human breast cancers; and, (iii) reports of PCR amplification of MMTV/HMLV sequences from breast cancers have been robustly disputed by four independent laboratories. Indeed positive PCR results may be readily explained by the mis‐amplification of host genomic DNA. Hence, the burden of proof currently lies with those who champion a viral cause for sporadic cases of breast cancer. Copyright © 2004 John Wiley & Sons, Ltd.