Study summary: The present study was designed to investigate whether bovine leukemia virus is related to U.S. breast cancer risk. Breast cancer in mice can be caused by a retrovirus, mouse mammary tumor virus, which is transmitted from mother to nurslings. Since humans consume more cow milk than human milk, the authors were interested in determining if a bovine virus might be capable of causing human breast cancer. Bovine leukemia virus is an oncogenic retrovirus that infects more than 90% of U.S. dairy herds and more than 14% of beef herds. Fewer than five percent of infected cattle actually develop leukemia, resulting in their removal from the human food supply. The remaining infected cattle remain healthy and are sources of beef and dairy products. There is some evidence that humans can become infected with bovine leukemia virus. Previous studies have found IgG antibodies to bovine leukemia virus in 39% of study volunteers. Furthermore, bovine leukemia virus capsid protein and proviral DNA have been found in human mammary epithelium. In the current case-control study, 213 samples of formalin-fixed breast tissue sections from 110 women with breast cancer and 103 breast cancer-free controls were evaluated. The authors tested for the presence of bovine leukemia virus and found that positive reactions were present only in mammary epithelium. Bovine leukemia virus was found in 59% of the breast cancer cases and 29% of the controls. Adjusting for donor age, race, catchment area, and length of time in formalin-fixed state, the odds ratio for breast cancer associated with the presence of bovine leukemia virus was 3.22 (95% confidence interval = 1.7-6.2, P < .0005). The data indicates that 39% of the breast cancer cases were attributable to BLV infection. 69% of the specimens from women with breast cancer had bovine leukemia virus proviral DNA in accompanying nonmalignant mammary epithelium. This suggests that cancer development may have been a rare, delayed event within a population of bovine leukemia virus-infected cells widespread in the breast tissue. The authors conclude that the study is promising first step in establishing a causal role for bovine leukemia virus in human breast cancer.