In our adolescent years, we would often snicker at other kids who were diagnosed with mononucleosis, as it was (and often still is) colloquially referred to as the “kissing disease.” However, in recent years mounting evidence has suggested that infection with Epstein-Barr virus (EBV) has become associated with various forms of cancer—which is certainly no laughing matter.

Alarmingly, a new study led by researchers from the Beth Israel Deaconess Medical Center (BIDMC) has revealed that infection with EBV may put some women at increased risk of developing breast cancer. Yet, results from the new study—“Epstein–Barr Virus Infection of Mammary Epithelial Cells Promotes Malignant Transformation”—published recently in EBioMedicine, may provide important implications for breast cancer screening and prevention in the future.

EBV, one of eight known viruses in the herpes family (human herpes 4 or HHV4) to infect humans, is also one of the most common viruses to infect humans and is best known as the cause of infectious mononucleosis. Although more than 90% of the world’s population carries EBV, most individuals experience no effects from infection. Nonetheless, in certain individuals, EBV has been linked to various cancers, including African Burkitt’s lymphoma, Hodgkin’s disease, nasopharyngeal carcinoma, gastric adenocarcinoma, and leiomyosarcoma.

Some more recent studies have tied EBV infection to breast cancer, yet it’s unclear how the virus may play a role in breast cancer development and/or progression. To investigate EBV’s role in breast cancer development, researchers cultured breast cells called primary mammary epithelial cells (MECs) in the presence of the virus.

The authors wrote that “EBV can infect primary MECs that express the receptor CD21. EBV infection leads to the expansion of early MEC progenitor cells with a stem cell phenotype, activates MET signaling and enforces a differentiation block. When MECs were implanted as xenografts, EBV infection cooperated with activated Ras and accelerated the formation of breast cancer.”

Interestingly, when the investigators subsequently analyzed the genes of MECs infected with EBV, they found genetic characteristics associated with high-grade, estrogen-receptor-negative breast cancer (an aggressive form of the disease).

“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. 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,” explained senior study author Gerburg Wulf, M.D., Ph.D., physician scientist in the hematology/oncology division at BIDMC and associate professor of medicine at Harvard Medical School. “While these are subtle changes, they may decades later, facilitate breast cancer formation.”

The researchers feel their findings establish a close link between EBV influencing the development of malignant breast cancer.

“We conclude that a contribution of EBV to breast cancer etiology is plausible, through a mechanism in which EBV infection predisposes mammary epithelial cells to malignant transformation, but is no longer required once malignant transformation has occurred,” the authors stated.

Dr. Wulf added that his team’s findings “further make the case for an EBV vaccine that might protect children from infection and later EBV-associated malignancies.”