Human Cytomegalovirus Seropositivity and Viral DNA in Breast Tumors Are Associated with Poor Patient Prognosis

Abstract

Human cytomegalovirus (HCMV) infects 40–70% of adults in developed countries. Detection of HCMV DNA and/or proteins in breast tumors varies considerably, ranging from 0–100%. In this study, nested PCR to detect HCMV glycoprotein B (gB) DNA in breast tumors was shown to be sensitive and specific in contrast to the detection of DNA for immediate early genes. HCMV gB DNA was detected in 18.4% of 136 breast tumors while 62.8% of 94 breast cancer patients were seropositive for HCMV. mRNA for the HCMV immediate early gene was not detected in any sample, suggesting viral latency in breast tumors. HCMV seropositivity was positively correlated with age, body mass index and menopause. Patients who were HCMV seropositive or had HCMV DNA in their tumors were 5.61 (CI 1.77–15.67, p = 0.003) or 5.27 (CI 1.09–28.75, p = 0.039) times more likely to develop Stage IV metastatic tumors, respectively. Patients with HCMV DNA in tumors experienced reduced relapse-free survival (p = 0.042). Being both seropositive with HCMV DNA-positive tumors was associated with vascular involvement and metastasis. We conclude that determining the seropositivity for HCMV and detection of HCMV gB DNA in the breast tumors could identify breast cancer patients more likely to develop metastatic cancer and warrant special treatment.

Human Cytomegalovirus Protein Expression Is Correlated with Shorter Overall Survival in Breast Cancer Patients: A Cohort Study

“…We previously published, in a smaller cohort, that patients with a low-grade HCMV-IE infection in primary colon and breast cancers have significantly longer time to brain metastasis and OS [ 35 ]. Other researchers have also reported an association between the risk of developing metastasis in patients with breast cancer who are seropositive for HCMV or HCMV DNA positive [ 52 ]. Furthermore, HCMV was correlated to a shorter relapse free survival in patients with breast cancer [ 53 ].…”

Detection of Human cytomegalovirus UL55 Gene and IE/E Protein Expression in Colorectal Cancer Patients in Egypt

“…reported in 2 studies higher prevalence of HCMV IE DNA and protein expression in CRC and breast cancer and their metastases to the brain with poor outcome [ 30 , 31 ]. Recently, two studies reported that HCMV gB DNA detection or expression of HCMV IE in breast cancer was found to be associated with shorter survival [ 32 , 33 ]. HCMV IE and E proteins were always detected in the cytoplasm in this study.…”

Human Cytomegalovirus Oncoprotection across Diverse Populations, Tumor Histologies, and Age Groups: The Relevance for Prospective Vaccinal Therapy

“…Cytomegalovirus has been reported as a risk factor for glioma, neuroblastoma, as well as breast cancer [3,4,[71][72][73][74]. Persons suffering from breast cancer who were CMV-seropositive or had CMV DNA in tumor tissue were significantly more likely to develop Stage IV metastatic tumors, hinting at an adverse oncomodulatory role of the virus, which promotes metastases [75]. An adverse effect of CMV was also noted elsewhere regarding the same pathology [76].…”