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The anatomic structures in which breast cancer invasion occurs arise as paired mammary glands developing from epithelial thickenings on the ventral surface of the 5-week fetus. A mesenchymal condensation occurs around burgeoning epithelial stalks around the 15th week. A physiologic "invasion" of this mesenchyme by cords of epithelial cells creates columns, which later give rise to the lobular organization of the mammary gland. With the onset of cyclical hormonal secretion at puberty, the hormonally responsive periductal stroma differentiates, and the epithelial columns develop into elongated lactiferous ducts terminating into terminal ducts that give rise to lobuloalveolar structures responsible for breast milk production. The adult breast consists of about 15 to 25 lobes, each associated with a major lactiferous duct terminating in the nipple. The glandular and ductal structures are embedded in specialized, hormone-responsive stromal tissue, which consists of adipose tissue admixed with collagenous and vascular elements, the relative abundance of which is largely responsible for the physical and radiographic appearance of the breast (Fig. 2-1).

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Figure 2-1
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Diagram of breast lobular architecture. This is a stylized depiction of one of the 15 to 25 lobes, or segments, of the human breast. The duct architecture is drawn in orange, illustrating the tree like branching of the ducts into the periphery of the gland. The stromal tissue (ST) is indicated as blank space, and contains the supporting vasculature, of which only the blood vessels are drawn. The gray areas surrounding the terminal duct/lobular units (TDLU) represent the specialized, more dense stromal tissues surrounding the ductal system.

The insert shows a magnified view of a ductule (D) and its lumen (DL), with a layer of epithelial cells (EC), which are connected by intercellular tight junctions. Interspersed between the epithelium and the delimiting basement membrane (BM) are myoepithelial cells (MEC). The periglandular stroma (PGS), containing specialized myofibroblasts (FB), also known as delimiting fibroblasts, commonly harbors inflammatory cell (IC) infiltrates.

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There are two distinct cell types forming the epithelium of the lactiferous ducts. The majority are columnar cells lining the surface, which are interspersed with basal cells. Basal cells are thought to give rise to both columnar cells and myoepithelial cells, which separate the epithelial layer from the basal lamina in larger ducts, becoming sparser and discontinuous in the smallest branches and the lobular glands. Throughout the duct system, including terminal ductules and acini, the epithelial and myoepithelial layers are invested by a basal lamina and surrounded by delimiting fibroblasts, separating them from stromal elements of the breast.

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Invasion is the second, and arguably the most consequential, of three pivotal milestones in the evolution of breast cancer. Invasion is preceded by the molecular events initiating carcinogenesis, and it may be followed by metastasis, the seeding of cancer cells to foci with no contiguous connection to the primary tumor. Before invasion occurs, the malignant cells, which may be morphologically ...

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