Anatomy of the Breast

Early Embryonic Development

The milk streak appears in the fourth week, when the embryo is 2.5 mm long. It becomes the milk line, or ridge, during the fifth week (2.5 to 5.5 mm). Mammary glands begin to develop in the 6-week-old embryo, continuing their proliferation until milk ducts are developed by the time of birth ³ ( Tables 2.1 and 2.2 ).

Embryologically, the mammary glands develop as ingrowths of the ectoderm into the underlying mesodermal tissue. In the human embryo, a thickened, raised area of the ectoderm can be recognized in the region of the future gland at the end of the fourth week of pregnancy. ⁴ The thickened ectoderm becomes depressed into the underlying mesoderm, the surface of the mammary area soon becomes flat, and it finally sinks below the level of the surrounding epidermis. The mesoderm in contact with the ingrowth of the ectoderm is compressed, and its elements become arranged in concentric layers, which at a later stage give rise to the gland’s stroma. The ingrowing mass of ectodermal cells soon becomes pouch or pear shaped and then grows out into the surrounding mesoderm as a number of solid processes that represent the gland’s future ducts. These processes, by dividing and branching, give rise to the future lobes and lobules and, much later, to the alveoli.

By 16 weeks’ gestation, the branching stage has produced 15 to 25 epithelial strips or solid cords in the subcutaneous tissue that represent future secretory alveoli. The smooth musculature of the nipple and areola are developed. By apoptosis of the central epithelial cells, branching and canalization continue. ⁵

Mid to Late Embryonic Development

By 32 weeks’ gestation the primary milk ducts appear and the mammary vascular system is completely developed. From 16 to 32 weeks, the secondary mammary anlage (primordium) develops. The secondary mammary anlage then develops, with differentiation of the elements of hair follicles, sebaceous glands, and sweat glands, along with the Montgomery glands, around the alveoli. Mesenchymal cells differentiate into the smooth muscle of the nipple and areola between 12 and 16 weeks’ gestation. ⁵ Thus far, development is independent of hormone stimulation. By 28 weeks’ gestation, placental sex hormones enter the fetal circulation and induce canalization in the fetus. ⁵

The lumina develop in the outgrowths, forming the lactiferous ducts and their branches. The lactiferous ducts open into a shallow epithelial depression known as the mammary pit . The pit becomes elevated as a result of the mesenchymal proliferation forming the nipple and areola. An inverted nipple is a result of the failure of the pit to elevate. ⁶ A lumen is formed in each part of the branching system of epithelial cell processes after 32 weeks’ gestation. This canalization produces the primary milk ducts at this time along with fur02ther development of the mammary gland vascular system.

Near term, about 15 to 25 mammary ducts form the fetal mammary gland ( Fig. 2.1 ). Duct and sebaceous glands coalesce near the epidermis. Parenchymal differentiation occurs with the development of lobular-alveolar structures that contain colostrum. This change occurs at 32 to 40 weeks and is called the end-vesicle stage .

Fetal Development

Morphologic developments in the fetal breast tissue occur in response to hormonal stimuli, similar to those in the maternal breast. ⁷ From 32 to 40 weeks’ gestation the mammary gland undergoes a four-fold increase in mass along with development of the nipple-areolar structure. Pigmentation of this structure also occurs at this time.

The Golgi system and abundant reticula with dilated cisternae filled with fine granular material are present in the cellular structure. Abundant mitochondria and lipid droplets are observed. Proliferation and conditioning of the epithelial cells are evident, and, in the last trimester, microvilli along the ductal lumen are accompanied by large cytoplasmic protrusions (see Table 2.2 ).

An extensive anatomic and histologic study of the human infant breast revealed an epithelial differentiation that followed a chronologic pattern, starting with secretory changes and apparently going through a period of apocrine metaplasia before the postsecretory changes and involution. ⁴ The embryonic fat probably plays a role in growth and morphogenesis of the ductal system. The male and female mammary glands develop in a similar fashion until puberty. ⁴

The terminal end buds, lateral buds, and lobules of three to five alveolar buds predominate in prepubertal tissue. Lobules of alveolar buds and lobules of up to 60 ductules predominate in pubertal females. In prepuberty, these epithelium-lined ducts will bud out to form alveoli when stimulated by hormones of menarche (see Fig. 2.1 ).

Fully formed, the breast is made up of skin, glandular tissue, supporting connective tissue, and protective fatty tissue.

Prepubertal Development

During childhood (prepuberty), the gland merely keeps pace with physical growth ² ( Figs. 2.2 and 2.3 ).

The molecular biology of mammary gland development depends on a combination of systemic mammotropic hormones plus local cell-to-cell interactions. ² A variety of growth factors mediate the local cell interactions. These factors include epidermal growth factor (EGF), transforming growth factor-β (TGF-β), fibroblast growth factor (FGF), and the Wnt gene families. In the developing breast these factors are thought to act in concert with systemic hormones. ²

Thelarche, or development of breast buds in females, commonly occurs between the ages of 8 and 13 years of age. Race, genetics, exercise, and body mass each can influence the age of thelarche. Concerns have been raised about earlier age of onset of thelarche. In a longitudinal cohort of 6 to 8 years of age, girls were followed from 2004 to 2011 in three geographic areas in the United States. Using Tanner staging, the age at onset of breast maturation was documented. Stage 2 onset varied by race/ethnicity, body mass index (BMI) at baseline, and site. Mean onset was 8.8, 9.3, 9.7, and 9.7 years for blacks, Hispanics, whites and non-Hispanics, and Asians, respectively. The greater the BMI, the younger the age of maturation. This study confirmed earlier onset of thelarche in girls in the last decade reported by other researchers. ⁸

Organogenesis

Organogenesis involves ductal and lobular growth and begins before and continues through puberty, resulting in growth of the breast parenchyma with its surrounding fat pad. When a girl is between 10 and 12 years of age, just before puberty, the ductal tree extends and generates its branching pattern, lengthening the existing ducts, dichotomously branching the growing ductal tips, and monopodially branching, with the growth of the lateral buds at the sides of the ducts ² ( Tables 2.2 and 2.3 ). During this period of rapid growth, the ducts can develop bulbous terminal end buds. The formation of alveolar buds begins within a year or two of the onset of menses. ¹⁰

Breast Size

At puberty, the breasts of a girl enlarge to their adult size, with the left frequently slightly larger than the right. ¹⁵ In a nonpregnant woman the mature breast weighs approximately 200 g. During pregnancy, breast size and weight increase; thus when a pregnant woman is near term, the breast weighs 400 to 600 g. During lactation the breast weighs 600 to 800 g (see Fig. 2.3 ).

Breast development has traditionally been assessed by physical examination with Tanner staging from infancy through pregnancy (see Fig. 2.3 ). There is an alternative using optical spectroscopy as a noninvasive procedure if necessary. ¹⁶

Breast Shape

The shape of breasts varies from woman to woman, just as do body build and facial characteristics. Genetic, racial, and dietary variations may be associated with discoidal, hemispheric, pear-shaped, or conical forms. ¹⁴ Typically, the breast is dome-shaped or conic in adolescence, becoming more hemispheric and finally pendulous in a parous woman.

Tail of Spence

Mammary glandular tissue projects somewhat into the axillary region. This is known as the tail of Spence ( Fig. 2.5 ). Mammary tissue in the axilla, which is connected to the central duct system, becomes more obvious during pregnancy and produces milk during lactation, when it may cause various symptoms (see Chapter 16 ). ¹⁷ The tail of Spence is distinguished from a supernumerary gland because it connects to the normal duct system. Occasionally, in normal women, small masses of breast tissue may grow through the deep fascia to the muscle below. This may explain some pain distribution when the breast is engorged.

Primary Breast Structures

The three major structures of the breast are skin, subcutaneous tissue, and corpus mammae. The corpus mammae is the breast mass that remains after freeing the breast from the deep attachments and removing the skin, subcutaneous connective tissue, and adipose tissue.

The breasts of an adult woman are paired and develop from a line of glandular tissue found in the fetus and known as the milk line . This milk streak, or galactic band, develops from the axilla to the groin during the fifth to seventh week of embryonic life. ² In the thoracic region, the band develops into a ridge and the rest of the band usually regresses ( Fig. 2.6 ).

Hypermastia

Hypermastia is the presence of accessory mammary glands, which are phylogenic remnants of the embryonic mammary ridge resulting from incomplete regression or dispersion of the primitive galactic band (see Fig. 2.6 ). Because of this origin, accessory nipples and glandular tissue may be found along these lines, which extend from the clavicular to the inguinal regions. Occasionally, supernumerary glands are found in the urogenital region, on the buttocks, or on the back. ¹⁸ The glands are derived from the ectoderm, and the connective tissue stroma is mesodermal in origin.

The accessory tissue may involve the corpus mammae, the areola, and the nipple. ¹⁸ Hypermastia occurs in 2% to 6% of women. The response of hypermastia to pregnancy and lactation depends on the tissue present and its location.

Box 2.1 defines other selected breast abnormalities.

Symmastia

Symmastia is a webbing across the midline between the breasts, which are usually symmetric. ⁴ A more common variation is the presternal confluence representing blending of breast tissue associated with large breasts. These abnormalities are ectodermal in origin and have many variations, from an empty skin web to the presence of significant glandular tissue. Little is known about their function, but several procedures exist for their surgical amelioration. ⁴

Amastia and Amazia

Congenital absence of the breast is called amastia , which is rare. When a nipple is present but no breast tissue, the condition is called amazia . Another term for this condition when it occurs in addition to a normal breast is hyperthelia .

Polythelia

Some have suggested a relationship between polythelia (supernumerary nipple) and renal defect. Polythelia also has been associated with renal agenesis, renal cell carcinoma, obstructive disease, and supernumerary kidneys. ¹⁸ Others have described associations with congenital cardiac anomalies, pyloric stenosis, ear abnormalities, and arthrogryposis multiplex congenita. ¹⁸

Poland Syndrome

Poland syndrome, first described in 1841 ( Box 2.2 ), includes absence of the pectoral muscle, chest wall deformity, and breast anomalies. ⁵ It is now known also to include symbrachydactyly, with hypoplasia of the middle phalanges and central skin webbing. Breast hypoplasia is underdevelopment of the breast. Although 90% of cases of breast hypoplasia are associated with hypoplasia of the pectoral muscles, 92% of women with pectoral muscle abnormalities have normal breasts. Box 2.2 lists types of breast hypoplasia, hyperplasia (overdevelopment), and acquired breast abnormalities.