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Cancers (Basel). 2010 Jun; 2(2): 752–772.
Published online 2010 Apr 30. doi:  [10.3390/cancers2020752]
PMCID: PMC3835103
PMID: 24281093
Viruses and Breast Cancer
James S. Lawson* and Benjamin Heng


Abstract
Viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. For over 50 years, there have been serious attempts to identify viruses which may have a role in breast cancer. Despite these efforts, the establishment of conclusive evidence for such a role has been elusive. However, the development of extremely sophisticated new experimental techniques has allowed the recent development of evidence that human papilloma virus, Epstein-Barr virus, mouse mammary tumor virus and bovine leukemia virus may each have a role in the causation of human breast cancers. This is potentially good news as effective vaccines are already available to prevent infections from carcinogenic strains of human papilloma virus, which causes cancer of the uterine cervix.

Keywords: breast cancer, viruses, etiology, human papilloma virus, mouse mammary tumor virus, Epstein-Barr virus, bovine leukemia virus

Note: In this paper we have followed the convention that malignancies of the human breast are referred to as breast cancer or breast tumors and malignancies of mouse mammary glands are referred to as mammary tumors.

1. Introduction

The identification of the causes of breast cancer is a crucial research issue for the development of effective prevention and treatment strategies. The aim of this review is to demonstrate that oncogenic viruses may have causal roles in human breast cancer. The main candidate viruses are human papilloma virus (HPV), mouse mammary tumor virus (MMTV), Epstein-Barr virus (EBV) and bovine leukemia virus (BLV). Each of these viruses has known oncogenic potential and all have been identified in normal and malignant human breast tissues. The past priority has been to confirm the identity of these viruses in breast tumors. The new priority is to determine whether or not they are causal rather than innocuous passengers invading pre-existing malignant tissues.

The formal search for the causes of human breast cancer began over 100 years ago. Despite cancer research expenditures exceeding $100 billion US dollars during the past 30 years, that hunt, and the basic causes of breast cancer, remain elusive [1]. However, sound progress has been achieved. The risk factors, as distinct from causal factors for breast cancer, have been well identified [2,3]. In addition, patterns of genetic susceptibility, again as distinct from causal patterns, have been both specifically and broadly defined [4]. The only specific known cause of breast cancer is exposure to radiation such as Japanese victims of the atomic bomb explosions, among whom young females were at special risk

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Overall Interpretation of the Evidence

The evidence that high risk HPVs and MMTV-like viruses are present in human breast tumors is in our view, conclusive. The evidence for the presence of EBV in human breast cancer is substantial but not conclusive. More research is required to determine whether BLV is present in human breast cancer. Whether these viruses are causal rather than passengers or invaders of existing malignant tissues, has not been established.

When considered in the context of the molecular based evidence, the presence of HPV associated precancerous koilocytes in normal and breast tumor tissues is very suggestive of a causal role. Similarly, the lifecycle and oncogenic characteristics of MMTV-like virus in humans is also suggestive of a causal role. The evidence for a causal role of EBV is less substantial but the identification of EBV Reed Sternberg cells in association with the molecular based evidence is suggestive.

If conclusive evidence for a causal role for these viruses can be developed, there will be a rational explanation of the heterogeneity of human breast cancer and above all a practical possibility of effective preventive and treatment approaches.