Abstract 4222: The prognostic impact of human cytomegalovirus infection in breast cancer
Authors: Touma Joel , Rahbar Afsar , Davoudi Belghis , Lindstrom Jonas Christoffer , Sauer Torill , Bukholm Ida Rashida , Vetvik Katja , Soderberg-Naucler Cecilia , Geisler Jurgen 
Published: August 2018

Abstract
Emerging evidence demonstrates a frequent presence of Human Cytomegalovirus (HCMV) proteins and nucleic acids in several primary malignant tumours including breast cancer (BC). HCMV maintains latency in monocytes and reactivates in an inflammatory or immune-suppressive state. The virus infection expresses more than 750 proteins, many has revealed both oncogenic and onco-modulatory properties which fulfil all the criteria for the hallmarks of cancer. HCMV is not believed to transform the host cell itself, but HCMV-encoded proteins are involved in cell cycle progression, interact with key proteins in the extrinsic and intrinsic apoptotic signalling cascade, and can induce drug resistance to chemotherapeutic agents. Earlier studies from our lab detected HCMV-IE (immediate early) and HCMV-LA (late antigen) proteins in &gt;90% of analysed primary breast cancer tumours, sentinel lymph node and brain metastasis, and that their prevalence is higher in advanced breast cancer. We have reported a significant correlation between HCMV and hormone receptor expression in a certain subgroup of breast cancer patients. The purpose of this study is to retrospectively investigate the prognosis and overall survival of 120 patients diagnosed and treated for breast cancer at the Akershus University Hospital, Norway, between 1996 and 2010. Material/methods: Formalin-fixed, paraffin-embedded, consecutively collected breast tumour samples and metastases, from clinically well-characterized patients were examined for HCMV-IE and HCMV-LA, using immuno-histochemical techniques. HCMV values was then correlated with BC subtypes: HER-2 positive, luminal A (LUM-A), luminal B (LUM-B) and triple negative breast cancer (TNBC). As well as time to: distant metastasis, loco-regional relapse and overall relapse. All data were defined in Kaplan-Meier curves for survival and a Cox regression model was fitted to each subgroup. Results: Both HCMV-IE and HCMV-LA was present in &gt;99% of the tissue samples analysed. We found a significant association between HCMV-LA and overall survival in TNBC patients (Hazard ratio 2.502; P-value 0.025). In addition, HCMV-LA was significantly correlated to the risk of local relapses in TNBC patients (Hazard ratio 4.149; P-value: 0.026). Finally, we also found the risk for local relapses and distant metastasis to be significantly tied to HCMV-LA levels in TNBC patients (Hazard ratio 4.126; P-value: 0.032). HCMV-LA and HCMV-IE levels were not found to be associated with either survival or risk for relapses in any other BC subtype. Conclusion: Our findings reveal a significant correlation between HCMV-LA expression and TNBC subtype concerning both risk of recurrence and overall survival. While no other BC subtype was found to be significantly influenced by the presence of HCMV-related proteins, the presence of HCMV-LA that imply an active HCMV infection seems to indicate a more aggressive disease when detected in TNBC patients.
Citation Format: Joel Touma, Afsar Rahbar, Belghis Davoudi, Jonas Christoffer Lindstrom, Torill Sauer, Ida Rashida Bukholm, Katja Vetvik, Cecilia Soderberg-Naucler, Jurgen Geisler. The prognostic impact of human cytomegalovirus infection in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4222.