Mice bred to be prone to breast tumours were vaccinated with an antigen expressed in human breast carcinomas.
The team at the Lerner Research Institute in Ohio found mice vaccinated with the antigen were tumour-free at 10 months of age, while all the control mice had developed mammary tumours.
Writing in the journal Nature Medicine, the researchers said human trials for a prophylactic vaccine against breast cancer could begin next year.
How relevant are the findings?
Researchers identified the protein alpha-lactalbumin as a target autoantigen.
This is produced in high amounts in most human breast carcinomas.
Six mice genetically prone to developing breast tumours were vaccinated with the antigen plus an adjuvant that boosts immune responses. Six control mice were immunised with adjuvant alone.
After 10 months, all of the control mice had developed mammary tumours.
However, cancer was not detected in mice immunised with alpha-lactalbumin. Researchers also found the vaccine slowed tumour growth in mice inoculated with cancer cells.
Can we expect a human vaccine?
Researchers said the vaccine protected against breast cancer without any detectable autoimmune-induced breast inflammation, as the target antigen is only expressed by tumours or during lactation.
This suggests a potential human vaccine could be given to healthy women who are either willing to avoid lactation or past child-bearing age.
Cancer Research UK's professor of medical oncology Robert Hawkins, based at the University of Manchester, said: 'This very early study describes an interesting approach to the prevention of breast cancer.
'It will be several years before this vaccine can be tested fully to assess its safety and effectiveness as a way to stop the disease developing in women.'
Caitlin Palframan, policy manager at the charity Breakthrough Breast Cancer, said: 'This research could have important implications for how we might prevent breast cancer in the future.'
But she also added that women can already take steps to reduce breast cancer risk, including reducing alcohol consumption, maintaining a healthy weight and taking regular exercise.