Abstract P4-06-01: Human mammary tumor virus, HMTV, is an MMTV-adapted human pathogen

Abstract

Abstract Forty percent of American women's breast cancers contain HMTV, a betaretrovirus 90-98% homologous to MMTV, the causative agent for breast cancer in mice. HMTV is reverse-transcribed and integrated into chromosomal DNA of human breast cells. MMTV contamination of our analyses has been definitively excluded. In 8% of unselected American mothers HMTV is found in cells in milk, but in 21% of milks from women previously biopsied for unconfirmed cancer suspicion. In breasts biopsied for suspicion of cancer before a later diagnosis of breast cancer, we see suggestive morphologic changes if the subsequent breast cancer is HMTV+. HMTV is infectious in vitro for B and T lymphocytes, dendritic cells, and human mammary epithelial cells. Infecting MCF-10 breast cell lines with HMTV produces molecular changes of epithelial-mesenchymal transition with upregulation of vimentin ,and downregualtion of E-cadherin. The excess of breast cancer in western European countries and their former colonies (age standardized rates of 47 to 92 per 100,000 per year) compared to Asian incidence (29 to 43 ASR/y) can 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 in breast cancers ranges 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 m. castaneus or m.musculus in the East with less. Ancient contamination of the food chain, and current lactational transfer perpetuate infection. HMTV poses a new and challenging dimension to breast cancer research involving diagnosis, molecular mechanisms, epidemiology, therapy and prevention. Citation Format: Holland JF, Jaffer S, Melana S, Nartey T, Gnjatic S, Pogo BG-T. Human mammary tumor virus, HMTV, is an MMTV-adapted human pathogen. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-06-01.