Abstract
Numerous independent groups from a range of countries have reported a high prevalence of Mouse Mammary Tumour Virus (MMTV)-like env sequences in human breast cancer specimens, including a prevalence of almost 40% in Australia. MMTV-like sag sequences and a completely integrated provirus have also been described. Recently, it was reported that MMTV is capable of productive infection of human breast cells in vitro. Conclusive demonstration of an association between MMTV and human breast cancer has remained elusive, and negative findings from a number of independent studies have questioned the role of MMTV as an aetiological agent. We used breast cancer specimens from women in the Australian Breast Cancer Family Study (ABCFS) who were diagnosed with first primary invasive breast cancer before the age of 40 years. Specimens were selected for higher grade cancers and for diagnosis relatively soon after childbirth. We searched for MMTV-like env sequences in tumour-enriched DNA using a nested PCR designed to detect all MMTV variants represented in GenBank, including those reportedly detected in human breast cancers. Forty-two specimens were deemed adequate for testing based on strong β-globin PCR. Despite the MMTV nested PCR regimen consistently detecting five copies of control plasmid against a background of MMTV-negative human genomic DNA, no MMTV env sequence was detected in any of the breast cancer specimens. Our findings appear inconsistent with previous reports on Australian breast cancer specimens but consistent with a growing number of independent negative reports internationally. We recommend caution in inferring a role for MMTV or a closely related virus in human breast cancer and suggest that universally regarded alternative lines of evidence such as highly specific serology data will be required to support such an association.
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Acknowledgements
We would like to thank the women who participate in this study and gave consent for access to their tumour samples. This study was supported by the NHMRC Australia Fellowship number 466668 awarded to JLH, who is also a Victorian Breast Cancer Research Consortium Group Leader. MCS is a National Health and Medical Research Council Senior Research Fellow and a Victorian Breast Cancer Research Consortium Group Leader. The authors would like to thank Ms Veronika Gazdik for histological assistance. The ABCFS has been funded by NHMRC, the Victorian Health Promotion Foundation, and the NSW Cancer Council.
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The authors declare no conflicting interests pertaining to this study.
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Park, D.J., Southey, M.C., Giles, G.G. et al. No evidence of MMTV-like env sequences in specimens from the Australian Breast Cancer Family Study. Breast Cancer Res Treat 125, 229–235 (2011). https://doi.org/10.1007/s10549-010-0946-4
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DOI: https://doi.org/10.1007/s10549-010-0946-4