Embryology/Development
The mammary glands develop from ectodermal ridges that form on the ventral surface of the embryo. They extend laterally from forelimb to hindlimb and constitute the milk line. These buds occur in multiple pairs and begin appearing at around 5 weeks of gestation. Most of the pairs regress during fetal development, except for one pair in the pectoral region that eventually develops into the two mammary glands. If buds along the milk line do not completely disappear, they will develop into ectopic glandular tissue. This ectopic mammary tissue is usually seen at the extreme ends of the mammary ridge, usually in the axilla or the vulva in the adult. This can occur as extra breasts (polymastia) or nipples (polythelia). Accessory mammary tissue is found in 2 - 6% of women.

At midpregnancy, the two fetal mammary buds destined to form breasts begin to grow and divide. Fifteen to 25 secondary buds are formed that are essentially the duct system in the mature breast.

Each secondary bud elongates into a cord, bifurcates and differentiates into two concentric layers of cuboidal cells and a central lumen. Secretory epithelium is derived from the inner layer of cells. These cells are responsible for milk production during lactation.

The outer layer of cells becomes myoepithelium and is responsible for the mechanism of milk ejection.

In the last 2 months of gestation, canalization of these epithelial cords occurs, as well as development of the branching lobuloalveolar glandular structures. The lactiferous ducts converge to form the mammary pit. Near birth, evagination of the mammary pit forms the nipple.

The earliest stage of fetal mammary gland development does not appear to be dependent on steroid hormones. Testosterone, however, influences actual growth and development after the 15th week of gestation. In the last weeks of gestation, the fetal breast is responsive to maternal and placental steroid hormones and prolactin. Secretory activity may be induced from the fetal mammary ducts. At birth, secretion of colostrum and palpable enlargement of the breast buds can be seen in both sexes. Regression typically occurs during the first 2 months of neonatal life.

In the female, adolescent breast development (thelarche) occurs with onset of cyclical estrogen and progesterone. Ductal growth and differentiation of periductal stroma is influenced by estrogen, growth hormones and glucocorticoids. With onset of ovulation, progesterone stimulates development of the alveoli and prepares the breast for possible future lactation.

Mary L. Gemignani
Memorial Sloan-Kettering Cancer Center

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