These oncogenic viruses may be present in breast tissue up to 11 years before BC manifestation. Further, multiple oncogenic viruses have been isolated in the same BC patient. Depending on the virus, it may interact to enhance or promote another virus's cancer-causing effects.
MMTV, a retrovirus, is passed on from lactating mice to their offspring, which later develop BC. MMTV has been isolated from human BC. MMTV is thought to be an external, not genetic, causal factor for BC as MMTV has been isolated from sporadic BC (30%), but it is not often found in hereditary forms (4%), such as BRCA1-associated BC. The form of MMTV identified in humans does not contain mouse mitochondrial DNA, but the gene sequence is 95% to 99% homologous with the form of MMTV isolated in mouse mammary tumors. MMTV antibodies are five times higher in women with BC than in controls. Proteins found in the MMTV envelope gene may be responsible for transforming normal human breast epithelial cells into malignant cells. Other oncogenic mechanisms that have been proposed, including insertional oncogenesis, resulting in gene mutations and interference with Apolipoprotein B Editing Enzyme (APOBEC3B), an antiviral enzyme.
HPV, like MMTV, can reduce the protective effect of APOBEC3B, resulting in an increased risk of MMTV-associated BC. Unlike in cervical cancer, the viral load of HPV is much lower in HPV-associated BC. HPV types 16 and 18 are more often associated with BC in Western populations, whereas HPV types 32, 52, and 58 are seen more commonly in BC patients from Asia and possibly, the Middle East. Women who develop HPV-associated cervical cancer are at a greater risk of developing HPV-associated BC. HPV-associated BC tends to occur in younger women. HPV transformation and oncogenic mechanisms are complex and may involve various HPV proteins, BRCA, COX-2, HER2, and EBV. HPV may be transmitted from the cervix to the breast via circulating extra-cellular vesicles (exosomes).
EBV has been associated with the development of lymphoma. It may interact with HPV, enhancing the ability of HPV to invade BC cells by interfering with APOBEC3B. Oncogenic mechanisms for EBV's involvement in BC may involve malignant transformation through activation of HER2/HER3 signaling cascades. EBV also leads to APOBEC3 genome instability. Other mechanisms for EBV's possible oncogenic effects in BC may include epithelial mesenchymal transition, BRCA-1 gene defect, or the involvement of EBV latent membrane proteins.
BLV is a retrovirus capable of integrating into a host's DNA, causing lifetime infection. It has also been associated with lymphosarcoma in cattle. The link to BLV and BC does not appear to be as strong as for the other viruses. There appear to be geographic variations between the association of BLV and BC with areas where unpasteurized milk consumption is commonly associated with higher rates of BLV in both dairy cattle and in human BC patients. It is postulated that BLV can be transmitted to humans by consumption of beef and cow's milk. However, a causal relationship between some human BCs and BLV has not been firmly established.
Pharmacists should be knowledgeable about the latest studies linking viruses to the possible development of BC as this may one day change how we treat oncologic conditions.
The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.
