Breast cancer is a leading cause of cancer-related death among women worldwide. A number of risk factors linked to breast cancer have been identified including age, sex, obesity, and family history. Recent investigations have also linked breast cancer to certain viral infections, including Epstein-Barr virus, human papilloma virus, and cytomegalovirus (“CMV”).
CMV is a widespread pathogen that infects between 50% and 80% of U.S. persons by age 40. In most individuals, primary infection with CMV is asymptomatic; however, serious symptoms can occur in patients with compromised immune symptoms. The possible relationship between CMV and cancer has been investigated for some time and increasing evidence suggests that CMV infection may be associated with several malignancies, including glioblastoma and breast cancer.
A recent investigation of breast cancer patients found that 100% of evaluated primary breast cancer samples were CMV positive. Researchers also detected viral proteins in neoplastic cells in sentinel lymph node (“SLN”) metastases. Analysis showed that virus positivity was mainly restricted to tumor cells in established tumors and metastases. The presence of CMV both in the primary breast tumor and in most SLN metastases, while adjacent healthy tissues remained CMV negative, supports the hypothesis that CMV may play an active role in tumorigenesis and metastasis of breast cancer.
While CMV is not considered an oncogenic virus at present, CMV appears to favor tumor progression through oncomodulatory effects that interfere with cellular properties. In other words, CMV infects tumor cells and upregulates their malignant properties, in a manner that directly changes the tumor cell genome. CMV proteins may alter the cell cycle, aid the cell in inhibiting apoptosis, and support malignant cells’ ability to evade the immune system response. Recent research has also demonstrated that secreted viral cytokines from CMV have immunosupressive capabilities, which mimic the cell signaling system of the host’s immune system, further downregulating the immune system response.
Researchers are continuing to study the relationship between CMV and breast cancer. Although direct evidence that CMV causes breast cancer is still lacking, some early data suggests that CMV infection may play a critical role in the survival and reproduction of breast cancer cells and could significantly contribute to breast cancer development and progression.
Further, analysis has shown that host immunity against CMV could play a significant role in keeping people free of breast cancer. A recent study demonstrated that levels of antibodies to CMV glycoprotein B (“gB”) were significantly higher in cancer-free controls than in patients with breast cancer. These results indicate that higher levels of anti-gB antibodies could play an important role in cancer immunotherapy.
With increasing evidence of a correlation, and a potentially symbiotic relationship between CMV and breast cancer, and considering that endogenous antibody responses appear to be protective, there is growing interest in exploring vaccination against CMV antigens as a potential component of immunotherapeutic strategies to treat breast cancer.