DENTON, TX — Cytomegalovirus (CMV), a herpesvirus that leads to lifelong infection, appears to play some role in breast cancer, according to a new study.
“CMV is not oncogenic, yet viral DNA and proteins have been detected in breast tumors, indicating possible contribution to tumor development,” wrote a study team led by Texas Woman’s University researchers and including participation from the Murtha Cancer Center of the Uniformed Services University of the Health Sciences in Bethesda, MD. “CMV encodes cmvIL-10, a homolog of human cellular IL-10 (cIL-10) with potent immunosuppressive activities. We investigated the relationship between CMV infection, cytokines, and breast cancer.”
For the study published in Breast Cancer Research & Treatment, the study team evaluated CMV serostatus and cytokine levels in plasma of women with benign breast disease (n = 38), in situ carcinoma (n = 41), invasive carcinoma, no lymph node involvement (Inv/LN−; n = 41), and invasive with lymph node involvement (Inv/LN+; n = 37).
Results indicated that half of the patient samples (n = 79) were CMV seropositive, although there was no correlation between CMV status and diagnosis (p = 0.75). For CMV+ patients, however, there was a trend toward higher CMV IgG levels in invasive disease (p = 0.172).
CmvIL-10 levels were higher in CMV+ in situ patients compared to the Inv/LN− and Inv/LN+ groups (p = 0.020) and, cIL-10 levels were higher in CMV+ in situ patients compared to the Inv/LN− and Inv/LN+ groups (p = 0.043), according to the report.
“The results were quite different in CMV− patients where cIL-10 levels were highest in Inv/LN− compared to benign, in situ, or Inv/LN+ (p = 0.019),” the authors pointed out. “African American patients were significantly associated with CMV+ status (p = 0.001) and had lower cmvIL-10 levels than Caucasian patients (p = 0.046).”
While no association was observed between CMV IgG and diagnosis, the study concluded that CMV infection influences cytokine production and contributes to altered cytokine profiles in breast cancer.
Background information in the study noted that Identification of factors that promote in situ tumors to become invasive is necessary to improve treatment options and increase overall survival in breast cancer patients. It stated that CMV is one factor linked to invasive breast cancer.”
CMV is a herpesvirus that establishes lifelong latent infection in 70% to 90% of the general population, according to the report, which added that CMV periodically reactivates but usually causes clinical disease only in immunocompromised people. Over a lifetime, however, CMV might reduce immune function, contribute to chronic conditions and promote tumor progression, it added.
The researchers advised that CMV has been associated with tumor progression and metastatic spread, explaining, “For example, CMV antibody levels are higher in women with invasive breast cancer than in healthy women. Also, CMV DNA and proteins have been found in tumor biopsy samples and are associated with more invasive tumors, higher tumor grade and poor overall survival.”
They posit CMV might affect the ability of cancer cells to evade immune detection, adding, “Of note, CMV encodes cmvIL-10, a viral cytokine and ortholog of human cellular interleukin-10 (cIL-10) with potent immune suppressive properties. Immune suppression in the tumor microenvironment is a key factor in progression from localized to invasive tumors.”
The authors concluded that, while CMV seropositivity is not strongly associated with breast cancer, there are significant differences in CMV IgG levels between breast cancer patients and healthy women.
“Our results clearly indicate a relationship between CMV status and systemic cytokine response in women with breast cancer, but these observations lead to more questions than they answer,” they explained. “In women with CMV, cytokine levels were higher in in situ and lower in invasive disease (LN−/LN+). But in women without CMV, cytokine levels were lower in situ and higher in invasive disease (LN−/LN+). We do not yet know whether this indicates that CMV infection may suppress anti-tumor responses, or if patients with CMV already have elevated cytokine levels due to virus infection, and those levels decrease in concert with tumor progression. While a profound difference in cytokine production was observed here between CMV+ and CMV− patients, more research is needed to fully understand the impact of CMV on breast cancer.”
- Spencer JV, Liu J, Deyarmin B, Hu H, Shriver CD, Somiari S. Cytokine levels in breast cancer are highly dependent on cytomegalovirus (CMV) status. Breast Cancer Res Treat. 2024 Aug 22. doi: 10.1007/s10549-024-07459-8. Epub ahead of print. PMID: 39172306.
