Nutritional supply to the tumor. The nutritional requirements of malignant breast tumors, which almost always originate within the milk duct system, are initially acquired by diffusion. With increasing size, the growth of solid tumors is dependent upon an increasing network of capillaries to supply it with oxygen and other essential nutrients (tumor-induced angiogenesis, or tumor angiogenesis). Impressive animal experiments have shown that malignant tumors up to a diameter of 1–2 mm are supplied with nutrients via diffusion. From a tumor diameter of 2–3 mm, the formation of a sufficient capillary network is essential for further tumor growth because the nutrient requirements can no longer be adequately met by diffusion over such distances.

Angiogenic growth factors. The growth of new, tumor-associated blood vessels is a complex physiological process. Endothelial cells, which can be in a dormant state for months or years and are necessary for the development of new blood vessel walls, are activated in angiogenesis by various growth factors such as the basic fibroblast growth factor (bFGF) and the vascular endothelial growth factor (VEGF). In addition, numerous other growth factors have been identified. During angiogenesis, angiogenic growth factors activate endothelial cells in preexisting blood vessels to release enzymes that degrade the basement membrane (lysis) and allow endothelial cells to escape. New capillaries develop by the proliferation and migration of these endothelial cells into the surrounding matrix as small sprouts. These newly formed capillaries have a discontinuous basement membrane with an elevated permeability and an increased loss of plasma proteins. The further development of capillaries to arterioles and arteries, as well as to venules and veins, constitutes the completion of the angiogenic process triggered by angiogenic growth factors and determined by the activation of certain biological messenger substances.