Breast cancer is the most commonly diagnosed form of cancer and the second leading cause of cancer deaths in western women. One out of 8 to 10 women will develop breast cancer during her lifetime. It is estimated that there are approximately 203,500 new cases in the year 2002 in the U.S. alone (Jemal et al., 2002). Among all diagnosed breast cancers, male breast carcinoma accounts for 1% of the cases. Advances have been made in breast cancer diagnosis, therapy and prevention. Significant progress in understanding of underlying genetic changes that contribute to the formation and progression of breast cancer have been made.

Human breast cancer arises from normal cells through the accumulation of multiple mutations, including loss-of-function mutations of tumor suppressor genes and activational mutations of oncogenes. Epigenetic changes, i.e. silencing of genes through promoter hypermethylationhas also been reported (reviewed in Widschwendter and Jones, 2002) Identification of tumor suppressor genes has been facilitated by the study of familial breast cancer. Approximately 10% of all breast cancer cases can be linked to heritable transmission of an autosomal dominant allele. Fifteen to twenty percent of these familial breast cancers can be accounted for by germ-line mutations in the breast cancer susceptibility genes BRCA1 and BRCA2. Rare germ-line mutations in p53 and CHK2 (Li-Fraumeni syndrome), PTEN (Cowden syndrome) and the serine threonine kinase STK11/LKB1 (Peutz-Jegher syndrome) account for another small fraction of the familial cases (Nathanson et al., 2001). Genes for the remaining familial clusters are unknown and may be caused by low-penetrance susceptibility genes. Causes for sporadic cancers are not clear, but many genes that contribute to growth and apoptosis have been found deregulated in sporadic breast cancer.

Mammography has long been the major technique for the screening of breast cancer. The US National Institute of Health recommends regular mammograms for women over 40, but there are debates regarding the effectiveness of this screening method (Nature, 415: 950, 2002). There are also emerging techniques for improved sensitivity of breast cancer imaging. For example, with the introduction of contrast agents and other advancements, magnetic resonance imaging (MRI) has the potential to become a useful adjuvant in breast imaging with the promise for detection, diagnosis, and staging of breast cancer (Orel and Schnall, 2001). But issues, including cost-effectiveness and standardized data interpretation, etc., have hampered its usage in clinical practice.

Early detection of breast cancer and optimal combination of surgery, chemotherapy, hormone therapy, and radiation therapy result in a decrease of local recurrence or development of metastatic cancer, contributing to the reduction of deaths by more than 50% (Hortobagyi, 2000). However, there is currently no effective cure for metastatic breast cancer.

The development of breast cancer models has provided important insights into breast tumor biology, and has facilitated the development and testing of novel therapeutic approaches for breast cancer. Spontaneous, chemical carcinogen-induced, or genetically modified mice are widely used as model systems. Carcinogen-induced mammary tumors in rats have also been extensively studied. There have been significant improvements in the technology of modeling human breast cancer in mice since the first transgenic mouse with mammary tumors was reported by Stewart et al. in 1984 (Stewart et al., 1984). Mouse strains harboring knockout of tumor suppressor genes, and mice strains carrying conditional alleles of oncogenes and tumor suppressor genes have been generated. The improvement has resulted in models that more accurately mimic the human situation in which genetic alterations occur in a subset of somatic cells. Some mouse models have been used in cancer prevention and cancer therapeutic studies. Importantly, mouse models have allowed the investigation of distinct pathways involved in breast cancer. These animal models are valuable for target validation in cancer drug discovery and may help alleviate the bottleneck in the drug discovery process.