Mills Ch3 Breast

70

SECTION II : Breast

TABLE 3.1 Major Steroid and Peptide Hormonal Influences on the Breast Hormone Effects Estrogen

Required for ductal growth and branching during adolescence Required for lobuloalveolar growth during pregnancy Required for induction of progesterone receptor Not necessary for maintenance of secretion or lactation Required for lobuloalveolar differentiation and growth Probable mitogen in normal estrogen-primed breast Not necessary for ductal growth and branching Stimulates breast mesenchyme during fetal development Causes mesenchymal destruction of mammary epithelium during critical period of testosterone sensitivity Enhanced ductal-alveolar growth Enhances protein synthesis in mammary epithelium Required for secretory activity (with glucocorticoids and prolactin) Stimulates epithelial growth after parturition Required for initiation and maintenance of lactation Enhances lobuloalveolar growth during pregnancy

Progesterone

During the last 8 weeks of gestation, the epithelial cords canalize and branch, forming lobuloalveolar structures as a result of mesenchymal paracrine effects. A depression in the epidermis, the mammary pit, forms at the convergence of the lactiferous ducts. The nipple forms by evagination of the mammary pit near the time of birth. During the last few weeks of gestation the fetal mam- mary gland is responsive to maternal and placental steroid hormones, and, as a result, the epithelial cells in the acinar units exhibit secretory activity. At the time of birth, with- drawal of the maternal and placental sex steroids stimulates prolactin secretion, which in turn stimulates colostrum secretion. Both male and female neonates exhibit palpa- ble enlargement of the breast bud. As the serum levels of maternal and placental sex steroid hormones and prolac- tin decline during the first month of life, secretory activ- ity ends, and the gland regresses and becomes inactive. At this stage, and until puberty, the breast consists primarily of lactiferous ducts that exhibit some branching without evi- dence of progressive alveolar differentiation, although some rudimentary lobular structures may persist. Another feature that may be seen in the fetal breast is extramedullary hematopoiesis, and this may persist in the periductal stroma until 4 months of age (Fig. 3.1) (9). ADOLESCENCE Adolescent breast development in the female begins with the onset of puberty and the cyclic secretion of estrogen and progesterone. However, a variety of other steroid and peptide hormones are also required for proper mammary gland development (Table 3.1) (8). The ducts elongate, branch, and develop a thickened epithelium primarily due to the influence of estrogen (Fig. 3.2) (10). The process FIGURE 3.1  Breast tissue from an infant showing ducts embedded in a loose connective tissue stroma. The stromal mononuclear cells are hematopoietic elements, indicative of persistent extramedullary hematopoiesis. (Courtesy of Theonia Boyd, MD, Children’s Hospital, Boston, MA)

Testosterone

Glucocorticoids Required for maximal ductal growth

Insulin

Prolactin

Human placental lactogen Able to substitute for prolactin in epithelial growth and differentiation Stimulates alveolar growth and lactogenesis in second half of pregnancy Growth hormone Required for ductal growth and branching during adolescence May contribute to lobuloacinar growth during pregnancy Thyroid hormone Increases epithelial response to prolactin May enhance lobuloacinar growth of ductal growth and branching is largely independent of progesterone. There is an increase in the density of peri- ductal connective tissue, also as a result of relative estrogen dominance. Deposition of stromal adipose tissue occurs, and it is this adipose tissue that is largely responsible for the enlargement and protrusion of the breast disk at this time. Cyclical exposure to progesterone following exposure to estrogen during ovulatory cycles promotes lobuloacinar growth, as well as connective tissue growth. Although the majority of breast development occurs during puberty, this process continues into the third decade, and terminal dif- ferentiation of the breast is only induced by pregnancy. Adapted from McCarty KS, Nath M. Breast. In: Sternberg SS, ed. Histology for Pathologists . Philadelphia, PA: Lippincott-Raven; 1997: 71–82.