Anatomy of the Breast, Axilla, Chest Wall, and Related Metastatic Sites

Form and Size

The mammary gland is located within the superficial fascia of the anterior thoracic wall. It consists of 15 to 20 lobes of glandular tissue of the tubuloalveolar type. Longitudinal fibrous connective stroma forms a latticed framework that supports the lobes; adipose tissue fills the space between the lobes. In the premenopausal female, the structure and stroma are dense; the organ remains mobile on the chest wall residing on the mammary bursae. Subcutaneous connective tissue surrounds the gland and extends as septae between the lobes and lobules, providing support for the glandular elements; however, the septae do not form a distinctive capsule around any component of the breast. The deep layer of the superficial fascia lies upon the posterior (deep) surface of the breast and resides upon the pectoral (deep) fascia of the thoracic wall. A distinct space, the retromammary bursa , can be identified surgically on the posterior aspect of the breast between the deep layer of the superficial fascia and the deep investing fascia of the pectoralis major, and contiguous muscles of the thoracic wall ( Fig. 4.3 ). As noted, the retromammary bursa contributes to the mobility of the breast on the thoracic wall. Fibrous thickenings of the connective tissue interdigitate between the parenchymal tissue of the breast. This connective tissue extends from the deep layer of the superficial fascia (hypodermis) and attaches to the dermis of the skin. These suspensory structures, called Cooper ligaments , distinctively insert perpendicular to the delicate superficial fascial layers of the cutis reticularis of the dermis, or corium, permitting remarkable mobility of the breast, while providing central support.

At maturity, the glandular portion of the breast has a unique and distinctive protuberant conical form. The base of the cone is roughly circular, measuring 10 to 12 cm in diameter and 5 to 7 cm in thickness. Commonly, breast tissue extends into the axilla as the axillary tail (tail of Spence). There is tremendous variation in the size of the breast, with frequent asymmetry in any individual. A typical nonlactating breast weighs between 150 and 225 g, whereas the lactating breast may exceed 500 g. In a study of breast volume in 55 women, Smith and colleagues reported that the mean volume of the right breast was 275.46 mL (SD = 172.65, median = 217.7, minimum = 94.6, maximum = 889.3) and of the left breast was 291.69 mL (SD = 168.23, median = 224, minimum = 106.9, maximum = 893.9).

The breast of the nulliparous female has a typical hemispheric configuration with distinct flattening above the nipple. The multiparous breast, which has experienced the hormonal stimulation associated with pregnancy and lactation, is usually larger, more dense, and more pendulous. As noted, during pregnancy and lactation, the breast increases dramatically in size, and with weight of milk assumes a more pendulous configuration. With increasing age, the postmenopausal breast usually decreases in volume, becoming somewhat flattened and gravitationally pendulous; thereafter, the organ is less dense, second to replacement of parenchyma with fat.

Extent and Location

The mature female breast extends inferiorly from the level of the second or third rib to the inframammary fold, which is at about the level of the sixth or seventh rib, and laterally from the lateral border of the sternum to the anterior or midaxillary line. The deep or posterior surface of the breast rests on portions of the deep investing fasciae of the pectoralis major, serratus anterior, and external abdominal oblique muscles and the uppermost superior extent of the rectus sheath. The axillary tail (tail of Spence) of the breast extends into the anterior axillary fold. The upper half of the breast, and particularly the upper outer quadrant, contains more glandular tissue than does the remainder of the breast. This anatomic fact accounts for the higher frequency of breast cancer in this quadrant.

Nipple and Areola

The epidermis of the nipple and areola is highly pigmented and somewhat wrinkled. It is covered by keratinized, stratified squamous epithelium. The deep surface of the epidermis is invaded by unusually long dermal papillae that allow capillaries to bring blood perfusion to its surface, giving the nipple-areola a pinkish color in young, fair-skinned individuals. At puberty, the pigmentation of the nipple and areola increases, and the nipple becomes more prominent. With the gravid state, the areola enlarges, and the degree of pigmentation increases. Deep to the areola and nipple, bundles of smooth muscle fibers are arranged radially and circumferentially in the dense connective tissue and longitudinally along the lactiferous ducts that extend up into the nipple. These muscle fibers are responsible for the erection of nipple that occurs in response to various stimuli (for a review of the anatomy of the nipple and areola, see Giacometti and Montagna ). The areola contains sebaceous glands, sweat glands, and accessory areolar glands (of Montgomery), which are intermediate in their structure between true mammary glands and sweat glands. The accessory areolar glands produce small elevations on the surface of the areola. The sebaceous glands (which usually lack associated hairs) and sweat glands are located along the margin of the areola. Whereas the apex of the nipple contains numerous free sensory nerve cell endings and Meissner corpuscles in the dermal papillae, the areola contains fewer of these structures. In a review of the innervation of the nipple and areola, Montagna and Macpherson reported observing fewer nerve endings than described by other investigators. They reported that most of the sensory endings were at the apex of the nipple. Neuronal plexuses are also present around hair follicles in the skin peripheral to the areola, and palpatory Pacinian corpuscles (vibratory pressure sensation and touch) may be present in the dermis and in the glandular tissue. The rich sensory innervation of the breast, particularly the nipple and areola, is of great functional significance. The suckling infant initiates a reflex chain of neural and neurohumoral events resulting in the release of milk and maintenance of glandular differentiation that is essential for continued lactation.

Inactive Mammary Gland

The adult mammary gland is composed of 15 to 20 irregular lobes of branched tubuloalveolar glands. The lobes, separated by fibrous bands of connective tissue, radiate from the mammary papilla, or nipple, and are further subdivided into numerous lobules. Those fibrous bands that connect with the dermis are the suspensory ligaments of Cooper. Abundant adipose tissue is present in the dense connective tissue of the interlobular spaces. The intralobular connective tissue is much less dense and contains little fat.

Each lobe of the mammary gland ends in a lactiferous duct (2–4 mm in diameter) that opens through a constricted orifice (0.4–0.7 mm in diameter) onto the nipple (see Fig. 4.3 ). Beneath the areola, each duct has a dilated portion, the lactiferous sinus. Near their openings, the lactiferous ducts are lined with stratified squamous epithelium. The epithelial lining of the duct shows a gradual transition to two layers of cuboidal cells in the lactiferous sinus and then becomes a single layer of columnar or cuboidal cells through the remainder of the duct system. Myoepithelioid cells of ectodermal origin are located within the epithelium between the surface epithelial cells and the basal lamina. These cells, arranged in a basketlike network, are present in the secretory portion of the gland but are more apparent in the larger ducts. They contain myofibrils and are strikingly similar to smooth muscle cells in their cytology.

Under light microscopy, epithelial cells are characteristically seen to be attached to an underlying layer called the basement membrane. With electron microscopy, the substructure of the basement membrane can be identified. The inner layer of the basement membrane is called the basal lamina. In the breast, the parenchymal cells of the tubuloalveolar glands, as well as the epithelial and myoepithelial cells of the ducts, rest on a basement membrane or basal lamina. The integrity of this supporting layer is of significance in evaluating biopsy specimens of breast tissue. Changes in the basement membrane have important implications in immune surveillance, transformation, differentiation, and metastasis.

Morphologically, the secretory portion of the normal mammary gland varies greatly with age and during pregnancy and lactation ( Fig. 4.2 ). In the inactive gland , the glandular component is sparse and consists chiefly of duct elements ( Fig. 4.4 ). Most investigators believe that the secretory units in the inactive breast are not organized as alveoli and consist only of ductules. During the menstrual cycle, the inactive breast undergoes slight cyclical changes. Early in the cycle, the ductules appear as cords with little or no lumen. Under estrogen stimulation, at about the time of ovulation, secretory cells increase in height, lumina appear as small amounts of secretions accumulate, and fluids and lipid accumulate in the connective tissue. Then, in the absence of continued hormonal stimulation, the gland regresses to a more inactive state through the remainder of the cycle.

Active Mammary Glands: Pregnancy and Lactation

During pregnancy, in preparation for lactation, the mammary glands undergo dramatic proliferation and development. These changes in the glandular tissue are accompanied by relative decreases in the amount of connective and adipose tissue. Plasma cells, lymphocytes, and eosinophils infiltrate the fibrous component of the connective tissue as the breast develops in response to hormonal stimulation. The development of the glandular tissue is not uniform, and variation in the degree of development may occur within a single lobule. The cells vary in shape from low columnar to flattened. As the cells proliferate by mitotic division, the ductules branch, and alveoli begin to develop. In the later stages of pregnancy, alveolar development becomes more prominent ( Fig. 4.5 ). Near the end of pregnancy, the actual proliferation of cells declines, and subsequent enlargement of the breast occurs through hypertrophy of the alveolar cells and accumulation of their secretory product in the lumina of the ductules.

The secretory cells contain abundant endoplasmic reticulum, a moderate number of large mitochondria, a supranuclear Golgi complex, and a number of dense lysosomes. Depending on the secretory state of the cell, large lipid droplets and secretory granules may be present in the apical cytoplasm. Two distinct products produced by the cells are released by different mechanisms. The protein component of the milk is synthesized in the granular endoplasmic reticulum, packaged in membrane-limited secretory granules for transport in the Golgi apparatus, and released from the cell by fusion of the granule’s limiting membrane with the plasma membrane. This type of secretion is known as merocrine secretion. The lipid, or fatty, component of the milk arises as free lipid droplets in the cytoplasm. The lipid coalesces into large droplets that pass to the apical region of the cell and project into the lumen of the acinus before their release. As they are released from the cell, the droplets are invested with an envelope of plasma membrane. A thin layer of cytoplasm is trapped between the lipid droplet and plasma membrane as lipid is being released. It should be emphasized that only a very small amount of cytoplasm is lost during this secretory process, classically known as apocrine secretion.

The milk released during the first few days after childbirth is known as colostrum. It has low lipid content, is high in carbohydrates, protein, vitamin A, and zinc, and contains considerable quantities of antibodies that provide the newborn with some degree of passive immunity. The lymphocytes and plasma cells that infiltrate the stroma of the breast during its proliferation and development are believed to be, in part, the source of the components of the colostrum. As the plasma cells and lymphocytes decrease in number, the production of colostrum stops and lipid-rich milk is produced.

Hormonal Regulation of the Mammary Gland

Physiologically enhanced production of estrogens and progesterone by the ovary at puberty induces the initial growth of the mammary gland. Subsequent to this nascent development, slight changes occur in the morphology of the glandular tissue with each ovarian, or menstrual, cycle. With pregnancy, the corpus luteum and placenta continuously produce estrogens (estrone, estradiol, estriol) and progesterone, which further stimulate proliferation and development of the mammary gland (see Fig. 4.5 ). The growth of the glands is also dependent on the presence of prolactin, produced by the adenohypophysis; somatomammotropin (lactogenic hormone), produced by the placenta; and adrenal corticoids. The level of circulating estrogens and progesterone diminishes acutely at parturition with the degeneration of the corpus luteum and loss of the placenta. The secretion of milk is then brought about by increased production of prolactin and adrenal cortical steroids. A neurohormonal reflex regulates the high level of prolactin production and release. The act of suckling by the infant initiates impulses from receptors in the nipple; these impulses provide feedback regulation for cells in the hypothalamus. The impulses also cause the release of oxytocin in the neurohypophysis. The oxytocin stimulates the myoepithelial cells of the mammary glands, causing them to contract and eject milk. In the absence of the suckling reflex stimulus, secretion of milk ceases, and the lobular glands regress and return to an inactive state. After menopause , the gland atrophies, or involutes. As the release of ovarian hormones is diminished, the secretory cells of the alveoli degenerate and disappear, but some of the ducts remain. The connective tissue also demonstrates degenerative changes that are marked by a decrease in the number of stromal cells and collagen fibers.