From Bittner to Barr: a viral, diet and hormone breast cancer aetiology hypothesis

In 1943, Bittner [1] demonstrated three cofactors in the development of spontaneous mammary tumours in mice. These were inherited susceptibility, hormonal influences, and a transmissible influence in mother's milk. This transmissible influence has since been shown to be a retrovirus, now known as the mouse mammary tumor virus (MMTV). This virus is oncogenic in the oestrogenic milieu of female mice of strains with a genetic susceptibility to mammary tumors [2]. Over the years, considerable indirect and limited direct evidence has emerged that suggests that an almost identical retrovirus to the MMTV, plus additional cofactors, may influence human breast carcinogenesis. This virus has become commonly known as HHMMTV. In addition, evidence has recently emerged that suggests additional viruses, such as the HPV and EBV, may also initiate or promote breast carcinogenesis [3,4,5,6,7].In 1971, Moore et al [2] demonstrated that human milk from women who are at high risk for breast cancer contains particles that are morphologically similar to the MMTV. As shown in Fig. 1, these particles have a 'mushroom' shape, with spikes on the viral envelope. Schlom et al [8] showed that such particles had reverse transcriptase activity, which is found in oncogenic retroviruses. Evidence has since accumulated showing the presence of a retrovirus that is homologous to MMTV in human breast cancer tissues [9,10], in cultures of normal human breast cells [11] and in cultures of human breast cancer cells [12,13].In 1971, Charney and Moore [14] showed that the serum of humans with breast cancer decreased the virility of MMTV, which suggested that antibodies to proteins of the virus may be present in humans. Antibodies that are reactive with MMTV are present at much higher levels in serum of humans with breast cancer than in serum of healthy women [15]. Such antibody levels in women with breast cancer vary from below 5% (in Chinese) to over 60% (in East Africans) among different populations [15].