Cytokine levels in breast cancer are highly dependent on cytomegalovirus (CMV) status

Abstract

Purpose Breast cancer accounts for 30% of all female cancers in the US. Cytomegalovirus (CMV), a herpesvirus that establishes lifelong infection, may play a role in breast cancer. CMV is not oncogenic, yet viral DNA and proteins have been detected in breast tumors, indicating possible contribution to tumor development. 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. Methods We 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 Fifty percent of the patient samples (n = 79) were CMV seropositive. There was no correlation between CMV status and diagnosis (p = 0.75). For CMV+ patients, 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). Similarly, cIL-10 levels were higher in CMV+ in situ patients compared to the Inv/LN− and Inv/LN+ groups (p = 0.043). 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). African American patients were significantly associated with CMV+ status (p = 0.001) and had lower cmvIL-10 levels than Caucasian patients (p = 0.046). Conclusion No association was observed between CMV IgG and diagnosis, but CMV infection influences cytokine production and contributes to altered cytokine profiles in breast cancer.