Abstract 4062: Human mammary tumor virus (HMTV) is a breast cancer pathogen

Abstract

Abstract Human mammary tumor virus (HMTV) a betaretrovirus 90-98% homologous to Mouse Mammary Tumor Virus (MMTV), the causative agent for breast cancer in mice, has been detected in approximately 40% of American women's breast cancers. Mouse DNA contamination has been definitively excluded by contamination-free guarantee techniques. In Western European countries and their former colonies, age standardized rates (ASR) of breast cancer incidence (47 to 92 per 100,000 per year) are higher than Asian incidence (29 to 43 ASR/y). This difference could be explained by excess HMTV-related breast cancer incidence. In 7 West European, American and Oceania countries, 30 to 60% contain HMTV, while in 5 Asian nations HMTV associated breast cancers range from 0 to 22%. Different indigenous murine species with disparate MMTV burdens parallel these findings: mus domesticus in the West with much MMTV in its genome, and mus castaneus or mus musculus in the East with less. HMTV is found in cells in milk of 8% of unselected American mothers and in milks of 21% of women previously biopsied for unconfirmed cancer suspicion. HMTV isolated from primary cultures of metastatic breast cells is able to infect In vitro, human mammary epithelial cells, B and T lymphocytes and dendritic cells. MCF10A breast cell line infected with HMTV shows molecular changes associated with epithelial-mesenchymal transition, such as up-regulation of vimentin, and down-regulation of E-cadherin. HMTV sequences were also shown to be more prevalent in inflammatory, gestational and familial breast cancers than in unselected sporadic samples, consistent with association with more aggressive breast cancer phenotypes. To establish a direct connection between the presence of HMTV sequences and metastatic breast cancer, we have found HMTV sequences in 94% of primary cultures of metastatic breast cells obtained directly from effusion fluids. HMTV present in primary breast tumors has been demonstrated in their metastatic axillary nodes. Taken together the results suggest an association between the presence of HMTV sequences and breast cancer aggressiveness. HMTV poses a new and challenging dimension in breast cancer research involving causation, diagnosis, molecular mechanisms, epidemiology, therapy and prevention. Citation Format: James F. Holland, Stella Melana, Teiko Nartey, Joseph Tripodi, Shabnam Jaffer, Anupna Nayak, Beatriz GT Pogo. Human mammary tumor virus (HMTV) is a breast cancer pathogen. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4062.