There is both good news and bad news in the fight against breast cancer. The good news is that there has been a steady decline in the death rate from breast cancer in this country and abroad since 1990. A 2% annual decrease in the death rate has resulted in an overall 25% reduction in cancer deaths in 2007 compared with 1990.1
Furthermore, the development of new treatments, such as trastuzumab and the aromatase inhibitors, has offered new hope to women with both early and advanced breast cancer. However, despite these clinical advances, as well as advances in our understanding of the biology of breast cancer, more than 44,000 women still die as a result of breast cancer annually in the United States alone. Recent analysis of the fall in death rates from breast cancer indicates that approximately half of this is the result of improved early detection through mammography screening, and the other half a result of improvements in adjuvant therapies for early-stage disease.2
In contrast, there has been relatively little change in the overall survival for women with metastatic breast cancer during the last several decades.3
Furthermore, even though recurrence rates have been significantly reduced by adjuvant therapies utilizing chemotherapy, hormonal therapy, and most recently, trastuzumab, an inhibitor of human epidermal growth factor receptor 2 (HER-2), recurrence still occurs in a substantial proportion of women after these treatments.
The heterogeneity and molecular complexity of breast cancer poses many challenges for the development of effective strategies to prevent and treat this disease. In addition, there is increasing support for the cancer stem-cell hypothesis, which, if correct, provides an explanation for the limitation of many current breast cancer models and suggests new strategies for breast cancer prevention and therapy. Classical models of carcinogenesis can be described as “stochastic” or “random,” in which any cell in an organ, such as the breast, can be transformed by the right combination of mutations.4
As a result, all or most of the cells in a fully developed cancer are equally malignant. It follows that strategies designed to treat and ultimately cure these cancers require the killing of all these malignant cells. The cancer stem-cell hypothesis is a fundamentally different model composed of two separate, but interrelated, components. The first is that tumors originate in tissue stem and/or progenitor cells through the dysregulation of the normally tightly regulated process of self-renewal.5
As a consequence, tumors contain a cellular component that retains key stem-cell properties including self-renewal, which initiates and drives carcinogenesis and differentiation, albeit aberrant, that contributes to tumor cellular heterogeneity.6
Although the concept that cancers arise from germ cells or stem cells was first proposed more than 150 years ago,7
it is only recently that advances in stem-cell biology have allowed for a more direct testing of the cancer stem-cell hypothesis. We will review recent evidence supporting this hypothesis and discuss its implications for breast carcinogenesis, cancer prevention, and cancer therapy.