Chemoprevention through nutritional and dietary changes may offer an important means of inhibiting the development and progression of
breast cancer, which would have a major impact on public health. Studies to assess the efficacy of potential chemopreventive compounds are difficult to perform in large human populations, whereas the use of genetically engineered mice (GEM) for preclinical testing offers several advantages. GEM models can be utilized to assess the inhibitory effects of nutritional and chemopreventive agents on well-defined oncogenic signaling pathways. Because several transgenic mouse models progress through a well-defined temporal series of stages leading to invasive
carcinoma formation, they may be particularly useful for determining
cancer stage-specific responses to nutritional and chemopreventive agents. The C3(1)SV40 T/
t-antigen transgenic mouse
mammary cancer model has been utilized for chemopreventive research in which mammary
tumors develop over a well-characterized time course. Several compounds have been shown to inhibit mammary
tumor development in this model, including
retinoids, di-fluoromethylornithine (DFMO),
dehydroepiandrosterone (
DHEA), antiangiogenic compounds and nonsteroidal antiinflammatory drugs (
NSAID). All of the chemopreventive agents used in the C3(1)Tag mammary mouse model appear to affect the promotion stage of
tumorigenesis, suggesting that these agents may be useful in inhibiting the transition of human
ductal carcinoma in situ (
DCIS) to invasive
carcinoma. Selective combinations of chemopreventive agents may be particularly useful for targeting multiple signaling pathways involved in
cancer development and progression leading to improved clinical responses. The application of gene expression profiling to chemopreventive studies will aid in the selection of appropriate models for preclinical testing and further define mechanisms of action.