Apoptosis and angiogenesis: two promising tumor markers in breast cancer (review)

Mammary epithelial homeostasis is dependent not only on the rate of cell proliferation, but also on apoptosis, a genetically programmed process of autonomous cell death. Cell death in tumours is commonly attributed to the induction of apoptosis. Angiogenesis is the process leading to the formation of new blood vessels, and it has been proposed that tumor growth is angiogenesis dependent. This review focuses on the biological role of apoptosis and angiogenesis in the development and progression of breast cancer; on the multiple genetic pathways regulating apoptosis and angiogenesis in breast cancer; and on clinical data demonstrating the prognostic significance of apoptosis and angiogenesis in breast cancer. Although evidence has suggested that decreased apoptosis and increased angiogenesis may play important roles in the biological aggressiveness of breast cancer, their precise molecular mechanisms in mammary tumorigenesis are unknown. There is accumulating evidence that apoptotic pathways and angiogenic status are controlled by a number of regulators, including inducers and inhibitors relevant to the pathogenesis of breast cancer. The inhibition of angiogenesis limits tumor growth by elevating the incidence of apoptosis. Several clinical studies have shown that apoptosis and angiogenesis are novel prognostic indicators in breast cancer, and they may have predictive value for the response to anticancer treatments. A recent study suggested that increased apoptosis plays a role in the response to hormonal treatment of breast cancer. Other studies have indicated that patients with breast cancer with high angiogenic activity have a worse prognosis. Overall, the evidence suggests that the progressive inhibition of apoptosis and induction of angiogenesis may contribute to tumor initiation, growth and metastasis in the pathogenesis of breast cancer. Apoptosis and angiogenesis may be valuable as markers for response in patients having primary or adjuvant chemotherapy for breast cancer. Furthermore, such tumor markers have the potential to develop a promising therapeutic strategy to regulate cell survival/death and neovascularization in breast cancer by the induction of apoptosis and/or the inhibition of angiogenesis.