At the time of surgery for
breast cancer,
cancer cells released from the primary
tumor have most likely entered blood or lymphatic vessels, leading to the development of
micrometastases.
Cancer cells directly produce
angiogenesis stimulators, provoke the release of stimulators bound to the surrounding extracellular matrix and induce macrophages to secrete
angiogenesis stimulators, thereby promoting angiogenesis.
Metastasis dormancy is characterized by a balance between cell proliferation and apoptosis and is thought to be controlled by increased apoptosis, indirectly induced by
angiogenesis inhibitors. Many patients with solid
tumors already have
micrometastases at the time of detection and surgical removal of their primary
tumors. Primary
tumor resection is believed to stimulate angiogenesis, initiating the proliferation of latent
micrometastases. Latent
micrometastases have already acquired angiogenic potential. The provision of additional
therapy to inhibit angiogenesis after surgery is therefore considered a rational approach. The effectiveness of dormancy
therapy should be evaluated in the prospective clinical trials of
chemotherapy with drugs such as
cyclophosphamide and UFT, which have been reported to inhibit angiogenesis as demonstrated by the numbers of circulating endothelial cells and circulating endothelial progenitors in peripheral blood before and after surgery in women with primary
breast cancer.