Development of the breast

The human mammary gland is derived from ectoderm. It is first visible in the 4-week embryo as a bud or nodule of epithelial tissue appearing along a line known as the milk crest. In the more developed embryo, this crest extends from the midaxilla to the inguinal region and may be the site of supernumerary breasts or nipples in the adult. The rudimentary epithelial nodule first becomes buried in embryonic mesenchyme, where it undergoes further differentiation, apparently under the influence of paracrine signals from the mesenchyme. Secondary epithelial buds form cellular cords that elongate, bifurcate and cavitate. These cords become the excretory and lactiferous ducts of the mammary gland.

The human mammary gland is a compound tuboalveolar structure composed of 15–25 irregular lobes radiating out from the nipple (Fig. 23.1). Individual lobes are embedded in adipose tissue and separated by dense layers of connective tissue. Each lobe is further subdivided into lobules, connected to the nipple by lactiferous ducts. The lactiferous ducts are lined by a stratified squamous epithelium. Loose connective tissue (stroma) surrounds the lactiferous ducts and permits their ready distension during lactation.

At birth, the breast is rudimentary and consists almost entirely of primitive lactiferous ducts. Although it may secrete a few drops of milk, called “witch’s milk,” this secretory function is short-lived and the breast quickly becomes quiescent until puberty. At puberty, ovarian estrogens stimulate the lactiferous duct system to grow. After menarche, exposure to cyclic progesterone induces further ductal growth and development of rudimentary lobules at the ends of the ducts. The breasts continue to grow for several years after menarche as the lactiferous ducts progressively subdivide, elongate and hollow out, and adipose tissue accumulates. However, complete lobular development and maturation will not occur in the absence of pregnancy.

At the beginning of pregnancy there is rapid growth and branching of the terminal portions of the rudimentary lobules under the influence of chorionic gondotropin. Vascularity increases dramatically. The pregnant woman often perceives these two changes as a “tingling” or ”tension” in her breasts. This sensation begins shortly after conception and may last throughout the first trimester. At about 8 menstrual weeks of pregnancy, sustained progesterone exposures initiates complete alveolar differentiation. True glandular acini appear as hollow alveoli lined with a single layer of myoepithelial cells. The highly branched myoepithelial cells form a loose network surrounding the alveoli. The alveoli connect to the larger lactiferous ducts through intralobular ducts. Alveolar secretion begins in the second trimester of pregnancy. By the third trimester, an immunoglobulin-rich secretion is seen distending the alveoli.

While the role of ovarian steroids in breast development is clearly clinically established (prepubertal gonadal failure is associated with absence of breast development), animal models suggest that other hormones may also be involved in human breast development. Insulin exposure causes multiplication of epithelial cells and formation of lobuloalveolar architecture. Complete cytologic and functional differentiation of the epithelial cells lining the alveoli requires exposure to cortisol, insulin and prolactin. Receptors for growth factors such as insulin-like growth factor 1 (IGF-1) and epidermal growth factor (EGF) have been demonstrated on human mammary cells, suggesting an important role for their ligands in breast development and function.