The mammary gland life cycle is exemplified by massive, physiologically dic
tated changes in cell number and composition, architecture, and functionali
ty. These drastic upheavals, by necessity, also involve the mammary endothe
lium, which undergoes angiogenic expansion during pregnancy and lactation f
ollowed by ordered regression during involution. In this review, we summari
se data obtained using the Mercer methyl methacrylate corrosion cast techni
que to analyse the mammary gland vasculature during normal development and
carcinogenesis. Concomitant with epithelial cell expansion, the mammary vas
culature grows during the first half of pregnancy by sprouting angiogenesis
whereas the last half of pregnancy and lactation are characterised by the
non-proliferative intussusceptive angiogenesis. The vasculature of the lact
ating gland is composed of a well-developed capillary meshwork enveloping t
he secretory alveoli with basket-like honeycomb structures. During involuti
on, regression of the vasculature is achieved by regional collapse of the h
oneycomb structures, capillary retraction, and endothelial attenuation. Thi
s process appears partly to involve apoptosis. However, an additional mecha
nism involving remodelling without cell death, which we have termed angiome
iosis, must exist to explain the morphological observations. Interestingly,
in mammary tumours of neuT transgenic mice, both sprouting and intussuscep
tive angiogenesis was observed simultaneously in the same nodules, a findin
g with potential implications for cancer therapy. The underlying molecular
mechanisms controlling angiogenic modulation in the mammary gland, particul
arly angiogenic regression and the endothelial:parenchymal interplay, are p
oorly understood. However, the data summarised in this review indicate that
precisely these molecular mechanisms offer novel alternatives for specific
and effective treatment of breast cancer. (C) 2001 Wiley Liss. Inc.