Epstein-Barr 'hit-and-run' infection may lead to breast cancer

Scientists have found evidence that Epstein–Barr virus (EBV) infection during adolescence may contribute to breast cancer development years later. According to results of a study in the July 2016 issue of EbioMedicine, EBV uses a “hit-and-run” tactic to infect mammary epithelial cells, which predisposes the cells to malignant transformation.

“We think that if a young woman develops EBV during her teenage years or later, her breast epithelial cells will be exposed to the virus and can be infected,” said lead investigator Gerburg Wulf, MD, PhD, a physician scientist in the Hematology/Oncology Division at Beth Israel Deaconess Medical Center (BIDMC) and an Associate Professor of Medicine at Harvard Medical School, in Boston, MA.

“While for most individuals, there will be no long-term consequences, in some the infection may leave genetic scars and change the metabolism of these cells,” Dr. Wulf explained. “While these are subtle changes, they may, decades later, facilitate breast cancer formation.”

If this concept proves to be true, it could lead to a major public health effort to reduce EBV infections and EBV-related breast cancer, the researchers speculated.

EBV is prevalent in humans—more than 90% of the world’s population has been infected. Although latent infection has no effect on most people, research has linked EBV to the etiology of certain cancers. But because EBV infection usually occurs years, even decades, before cancer develops, scientists have been stymied in their efforts to determine how exactly how EBV may cause cancer.

For this investigation, Dr. Wulf and colleagues obtained cultures of mammary epithelial cells (MECs), which they infected with EBV. They injected these cultures into the mammary fat of lab mice, and then watched for developing tumors. Analysis of the resulting tumors showed that EBV infection cooperated with cancer-causing proteins (activated Ras) to accelerate the formation of breast cancer.

When the investigators performed genetic analysis of MECs infected with EBV, they found clinicopathological characteristics of high-grade, estrogen-receptor-negative breast cancer, p53mutation, and poor survival.

Interestingly, not all EBV-infected tumors had EBV DNA. This led the researchers to believe that EBV used a “hit-and-run” mechanism—that is, once EBV infection predisposed MECs to become malignant, the virus was no longer needed after the cells became cancerous.

If additional research finds that EBV infection does indeed contribute to breast cancer, then this discovery opens the door for a potentially major impact on public health.

“The findings further make the case for an EBV vaccine that might protect children from infection and later EBV-associated malignancies,” Dr. Wulf predicted.