Abstract

Breast cancer (BC) remains a significant global health challenge, highlighting the need for continued research into novel risk factors, diagnostic approaches, and personalized treatments. Among emerging risk factors, viral infections have been implicated as potential contributors to breast carcinogenesis and BC progression. Recent evidence suggests that specific oncogenic strains of human cytomegalovirus (HCMV) may have the capacity to transform human mammary epithelial cells. This review assesses clinical data regarding HCMV presence in both tumor and non-tumor breast tissues, examining the role of HCMV oncoproteins in BC development and progression. Current findings indicate a higher prevalence of HCMV infection in breast carcinomas compared to non-tumor tissues, associated with an elevated risk of BC. Additionally, the HCMV-driven breast carcinogenesis model proposed here suggests that HCMV oncoproteins may activate multiple oncogenic pathways, fostering cell proliferation, survival, and tumor development. A deeper understanding of the role of HCMV in BC could enhance risk stratification and support the creation of targeted therapeutic strategies.; Human cytomegalovirus (HCMV) has been suggested as a potential contributor to breast cancer (BC) development, though its role remains the subject of ongoing debate. This review examines the epidemiological evidence linking HCMV infection to BC and explores the molecular mechanisms by which the virus may contribute to cancer initiation and progression. The current literature reveals a higher prevalence of HCMV in BC tissues compared to normal or benign breast tissues. Furthermore, in vitro studies suggest that HCMV can activate key pathways involved in tumor growth, survival, and metastasis. The virus may also influence the tumor microenvironment and immune responses, fostering conditions that promote cancer progression. Finally, the evidence indicates that certain HCMV strains possess oncogenic properties and may be associated with more aggressive BC subtypes. However, further research is necessary to confirm these findings and translate them into practical clinical applications. © 2025 by the authors.; © 2025 by the authors.