THE BREAST

POSITION AND STRUCTURE

The breast is shown in its partially dissected state in the upper part of the plate and below in sagittal section. The size of the breast is variable, but in most instances it extends from the second through the sixth rib, and from the sternum to the anterior axillary line, with an axillary tail in the outer and upper portions, which can be palpated along the outer border of the pectoralis major muscle. The mammary tissue lies directly over the pectoralis major muscle and is separated from the outer fascia of this muscle by a layer of adipose tissue, which is continuous with the fatty stroma of the gland itself.

Fatty deposits surround and intermix with the glandular elements and make up a significant portion of the breast structure, providing much of its bulk and shape. The ratio of fatty to glandular tissue varies among individuals and with the stage of life; with menopause, the relative amount of fatty tissue increases as the glandular tissue declines. A rich vascular and lymphatic network (discussed subsequently) supplies the breasts.

The sensory innervation of the breast follows the normal distribution of the dermatomes and is mainly derived from the anterolateral and anteromedial branches of thoracic intercostal nerves T ₃ -T ₅ . Supraclavicular nerves from the lower fibers of the cervical plexus also provide innervation to the upper and lateral portions of the breast. Sensory enervation of the nipple is from the lateral cutaneous branch of T ₄ .

The center of the dome-shaped, fully developed breast in the adult woman is marked by the areola mammae, a circular, pigmented skin area from 1.5 to 2.5 cm in diameter. The surface of the areola appears rough because of large, somewhat modified sebaceous glands, the glands of Montgomery, which are located directly beneath the skin in the thin subcutaneous tissue layer. The fatty secretion of these glands is said to lubricate the nipple. Bundles of smooth muscles in the areolar tissue serve to stiffen the nipple for a better grasp by the suckling infant.

The nipple or mammary papilla is elevated a few millimeters above the breast and contains 15 to 20 lactiferous ducts surrounded by fibromuscular tissue and covered by wrinkled skin. Partly within this compartment of the nipple and partly below its base, these ducts expand to form the short sinus lactiferi or ampullae in which the milk may be stored. These ampullae are the continuation of the mammary ducts, which extend radially from the nipple toward the chest wall, and from them sprout variable numbers of secondary tubules. These end in epithelial masses forming the lobules or acinar structures of the breast. The number of tubules and the size of the acinar structures vary greatly in different individuals and at different periods in life. In general, the terminal tubules and acinar structures are most numerous during the childbearing period and reach their full physiologic development only during pregnancy and lactation. These epithelial structures constitute collectively the parenchyma of the gland. The stroma is composed of a mixture of fibrous and fatty tissue, and, in the absence of pregnancy and lactation, the relative amounts of fatty and fibrous tissue determine the size and consistency of the breast.

The enveloping fascia of the breast is continuous with the pectoral fascia. It subdivides the glands into lobules and sends strands into the overlying skin, which, in the upper hemisphere, are known as the suspensory ligaments of Cooper. Because these strands are not taut, they allow for the natural motion of the breast, but result in breast ptosis as these ligaments relax with age.

BLOOD SUPPLY

The sources of the abundant vascular supply of the mammary gland are the descending thoracic aorta, from which the posterior intercostal arteries branch off; the subclavian artery, from which the internal mammary artery arises; and the axillary artery, serving the mammary gland through the lateral thoracic and sometimes through another branch, the external mammary artery. Additional blood may be supplied by branches from the thoracodorsal artery and the thoracoacromial artery, which is a short trunk that arises from the forepart of the axillary artery, its origin being generally overlapped by the upper edge of the pectoralis minor.

The intercostal branches of the internal mammary artery, the thoracic portion of which lies behind the cartilage of the six upper ribs just outside the parietal layer of the pleura, supply the medial aspect of the gland. The lateral cutaneous branches of the third, fourth, and fifth aortic intercostal arteries enter the gland laterally. The lateral cutaneous branches of the intercostal arteries penetrate the muscles of the side of the chest and then divide into anterior and posterior rami, of which only the anterior rami reach the mammary gland. The branches from the lateral thoracic artery, which descends along the lower border of the minor pectoral muscle, approach the gland from behind in the region of the upper outer quadrant. One of these branches (in women more developed than the other branches) is the external mammary artery, which turns around the edge of the pectoralis major muscle, where it could be seen in the picture if the breast were lifted up. An extensive network of anastomoses exists between the lateral thoracic artery and those vessels deriving from the internal mammary artery; the latter also anastomoses with the intercostal arteries, so that two or even three of the main sources supply many parts of the gland. The ramifications of all three main arteries form a circular plexus around the areola, which ensures the blood supply of the nipple and areola. The breast skin depends on the subdermal plexus for its blood supply. This plexus is in communication with underlying deeper vessels supplying the breast parenchyma, where a second plexus from the same main vessels is formed in the deeper regions of the gland.

A number of variations of this vascular distribution exist and should be considered to avoid the danger of necrosis, for example, in circular incisions around the nipple. The rich blood supply of the breast allows for a variety of surgical procedures, therapeutic or cosmetic, to be performed while ensuring the viability of the skin flaps and breast parenchyma after surgery. This advantage can become a disadvantage by providing a point of systemic spread for infection or malignancy.

The veins follow the course of the arteries. Venous drainage is primarily into the axillary vein, with some blood draining into the internal thoracic vein. The axillary vein has an irregular anatomy, which complicates surgery under the arm. The surface veins encircle the nipple and carry blood to the internal mammary, axillary, and intercostal veins, and to the lungs. These connections can allow breast cancer cells to travel to the lungs via these surface veins to form metastatic tumors. The intercostal veins join a complex network of vertebral veins in and around the spine, providing an additional path for cancer to spread to bone.

The veins draining the breast parenchyma are subject to inflammation and thrombosis as in other areas in the body. This can result in Mondor disease and thrombophlebitis, respectively.

LYMPHATIC DRAINAGE

The lymphatic distribution of the breast is complex. The mammary gland has a very rich network of lymph vessels, which is separated into two planes, the superficial or subareolar plexus of lymphatics and the deep or fascial plexus. Both originate in the interlobular spaces and in the walls of the lactiferous ducts. The lymph nodes that drain the breast are not linked in a straight line; instead, they are staggered, variable, and fixed within fat pads. This arrangement complicates lymph node removal during breast cancer surgery.

Collecting lymph from the central parts of the gland, the skin, areola, and nipple, most of the superficial plexus drains laterally toward the axilla, passing first to the anterior pectoral group of nodes, which are often referred to as the low axillary group of glands. The anterior pectoral nodes, four to six in number, lie along the border of the pectoral muscles adjacent to the lateral thoracic artery. The drainage passes thence to the central axillary nodes, which lie along the axillary vein, or to the midaxillary nodes. From there, the drainage is to the subclavian nodes at the apex of the axilla where the axillary and subclavian veins join. The axilla contains a varying number of nodes, usually between 30 and 60. Approximately 75% of the breast lymphatic drainage goes to these axillary regional nodes.

The deep fascial plexus extends through the pectoral muscles to Rotter lymph nodes, situated beneath the pectoralis major muscle, and thence to the subclavian nodes. This is known as Groszman pathway. The rest of the fascial plexus, for the most part, extends medially along the internal mammary artery via the internal mammary nodes to the mediastinal nodes. Other paths of lymphatic drainage proceed from the lower and medial portions of the breast. One of these is the paramammary route of Gerota, through the abdominal lymphatics to the liver or subdiaphragmatic nodes. Another is a cross-mammary pathway, via superficial lymphatics to the opposite breast and opposite axilla. Metastases from one breast across the midline to the other breast or chest wall occur occasionally via this pathway. From the lower medial portion of the breast, some lymphatics of the fascial group drain, passing beneath the sternum, to the anterior mediastinal nodes situated in front of the aorta. Lymphatic drainage to the intercostal glands, which are located posteriorly along the vertebral column, and to subpectoral and subdiaphragmatic areas may also occur.

Lymph nodes play a central role in the spread of breast cancer. The axillary lymph nodes are particularly important, as they are among the first places that cancer is likely to metastasize from the breast. This cluster of lymph nodes is often referred to as level I nodes. (Level II nodes are located underneath the pectoralis minor muscle, and level III nodes are found near the center of the collarbone.) Other metastatic routes include lymphatics adjacent to the internal mammary vessels, allowing direct spread into the mediastinum.

Lymph drainage usually moves toward the most adjacent group of nodes: this is the basis for the concept of sentinel node mapping in breast cancer. In most instances, breast cancer spreads in a predictable way within the axillary lymph node chain based on the location of the primary tumor and the associated sentinel nodes. However, lymphatic metastases from one specific area of the breast may be found in any or all of the groups of regional nodes. Despite this observation, the concept of using a sentinel node to detect spread is still useful because in only about 3% of these women does the positive node occur outside of the axilla.

DEVELOPMENTAL STAGES

In a human newborn at birth, in the female as well as in the male, the mammary glands have developed sufficiently so that they appear as distinct hemispheroidal elevations, palpable as movable soft masses. This is especially prominent in postterm infants. Histologically, a number of branching channels with layers of lining cells and plugs of basal cells at their ends, the future milk ducts and glandular lobules, respectively, can easily be recognized. In a great number of infants an everted nipple is observed, and in about 10% a greatly enlarged gland can be palpated, a condition that received the unfortunate name of mastitis neonatorum, though no signs of inflammation exist. These early glandular structures may produce a milklike secretion, the “witch's milk,” starting 2 or 3 days after birth. All these neonatal phenomena in the breast are the result of the very intensive, maternal estrogen–driven developmental processes in the last stages of intrauterine life. The changes subside within the first 2 to 3 weeks of life. It is during this period that the breast undergoes marked involutional changes leading to the quiescent stage, which is characteristic of infancy and childhood. During these periods, the male and the female glands consist of a few branching rudimentary ducts lined by flattened epithelium, surrounded by collagenous connective tissue.

For most girls, the first sign of puberty is usually the appearance of breast budding. In the United States, this early breast change begins at an average age of 10.8 (±1.1) years of age. With the onset of puberty and during adolescence, follicular ripening in the ovaries, in response to follicular-stimulating hormone (FSH) of the anterior pituitary gland, is accompanied by an increased output of estrogen. In response to the latter, the mammary ducts elongate and their lining epithelium reduplicates and proliferates at the ends of the mammary tubules, forming the sprouts of the future lobules. This growth of ductal epithelium is accompanied by growth of periductal fibrous tissue, which is largely responsible for the increasing size and firmness of the adolescent female gland. During this period, the areola and nipple also grow and become pigmented.

With the onset of maturity, that is, when ovulation occurs and the progesterone-secreting corpora lutea are formed, the second stage of mammary development occurs. It is essentially concerned with the formation of the lobules and acinar structures. Although in the adult woman, progesterone always asserts its influence when estrogen is simultaneously present, overwhelming experimental evidence indicates that this beginning unfolding of the lobules is a specific effect of progesterone. This gives the mammary gland the characteristic lobular structure found during the childbearing years. This differentiation into a lobular gland is finished approximately 1 to 1½ years after the first menstruation, but further acinar development continues in proportion to the intensity of the hormonal stimuli during each menstrual cycle and especially during pregnancies. Fat deposition and formation of fibrous stroma contribute to the increasing size of the gland in the adolescent period.

The predictable sequence of breast development brought on during adolescence forms one part of the sexual maturation scale (Tanner staging) that is used to assess the degree and sequence of pubertal development. In 1969, Marshall and Tanner defined five stages of breast development and pubic hair development that are combined and called Tanner, or pubertal, stages 1 through 5. For most girls, breast budding is the earliest sign of puberty and menarche the latest.

FUNCTIONAL CHANGES AND LACTATION

The maturational changes in hormones from the anterior pituitary gland and ovary are major factors in the development and functioning of the mammary gland. Follicle-stimulating and luteinizing hormones are indispensable for the production of ovarian estrogen and progesterone, which, in turn, control mammary gland development. These are necessary but not sufficient to prepare the breast for lactation.

The mammary gland of a nonpregnant woman is inadequately prepared for secretory activity. Only during pregnancy do those changes normally occur that make milk production possible. In the first trimester of pregnancy, the terminal tubules sprouting from the mammary ducts proliferate in order to provide a maximum number of epithelial elements for future acinar formation. In the midtrimester, the reduplicated terminal tubules are grouped together to form large lobules. Their lumina begin to dilate, and the acinar structures thus formed are lined by cuboidal epithelium; occasional acini contain small amounts of colostrum secretion. In the last third of pregnancy, the acini formed in early and midpregnancy are progressively dilated. The high levels of circulating estrogens and progesterone during pregnancy are responsible for these alterations in the breast.

During pregnancy, as estrogen levels increase, there is a parallel hypertrophy and hyperplasia of the pituitary lactotrophs. An increase in prolactin occurs soon after implantation, concomitant with the increase in circulating estrogen. Circulating levels of prolactin steadily increase throughout pregnancy, peaking at about 200 ng/mL during the third trimester. This rise is in parallel with the continued increase in circulating estrogen levels over this time. Despite these elevated prolactin levels, lactation does not occur because estrogen inhibits the action of prolactin on the breast (most likely blocking interaction with the prolactin receptor).

Following childbirth, active secretion begins in the now maximally dilated acinar structures as a result of the stimulation by prolactin from the anterior pituitary gland and by the nursing of the infant. A day or two following delivery of the placenta, both estrogen levels and prolactin levels decline rapidly and lactation is initiated. Prolactin levels reach basal concentrations after 2 to 3 weeks in women who do not breastfeed. In nursing women, basal levels of prolactin decline to the nonpregnant range within 6 months after parturition; after each act of suckling, prolactin increases markedly.

Lactation, starting 3 to 4 days after delivery, is stimulated and maintained through the mechanical act of sucking. In addition to prompting a pulse in prolactin, stimulation of the areola causes the secretion of oxytocin, which is responsible for the letdown reflex and ductal contraction that expels the milk. Therefore, it is through these feedback mechanisms that suckling ensures further milk production.

Prolactin has not been shown to affect the macro- or microscopic changes in the gland. Its only function is to stimulate milk secretion after the tissues have been previously adequately prepared (by estrogen and progestin). During consistent breastfeeding, follicular ripening and ovulation are suppressed for approximately 6 months.

The secretion of true milk takes place in the epithelial lining of the dilated acini by cuboidal or columnar cells with nuclei at their bases or tips. This epithelium rests on a narrow band of connective tissue that encloses thin-walled capillaries. Secretory globules and desquamated epithelial cells distend the acini and their afferent channels. During the height of lactation, milk secretion and its storage account for one-fifth to one-third of the breast volume.

Nipple and breast stimulation can also increase prolactin levels in the nonpregnant woman. Prolactin levels normally rise following ingestion of the noonday meal and may increase in response to exercise, sleep, and stress. For these reasons, prolactin levels normally fluctuate throughout the day, with maximal levels observed during nighttime sleep and in the early afternoon.

POLYTHELIA, POLYMASTIA, HYPERTROPHY

Congenital anomalies of the breast, such as agenesis or amastia, aplasia, or the absence of nipple and/or areola, are extremely rare. (Athelia or amastia is sometimes associated with Poland syndrome, consisting of absent chest wall muscles, absence of ribs 2 to 5, and deformities of hands or vertebrae.) An increase in the number of mammae or of nipples only is encountered somewhat more frequently. Both these conditions find ready explanation in the embryologic development of the breast. During the 6th to the 12th week of fetal life, the mammary glands first develop as solid down growths of the epidermis that extend into the mesenchyme from the axilla to the inguinal regions—the milk lines. Later, these ridges disappear, except in the pectoral area where the normal breast develops.

Accessory or supernumerary nipples (polythelia) occur in about 1% of men and 2% of women. These cases are sporadic; although familial polythelia is recognized, it is extremely rare. Most supernumerary nipples resemble a mole or birthmark and are only recognizable because of their anatomic location. Most often the supernumerary nipples are found 5 or 6 cm below the normal pair and toward the midline. They are usually not associated with significant amounts of underlying mammary tissue. The accessory nipples without accessory mammary tissue are found anywhere in the course of the milk lines of the embryo. In the adult, this extends from the axillary to the inguinal regions. In the regions below the breast, the milk line runs medially to the normal nipple; above the breast it runs laterally toward each axilla. Supernumerary mammary glands (polymastia) situated laterally are more apt to be of considerable size and to undergo normal lactation compared with those situated medially. Bilateral axillary breasts that are of small size may develop during pregnancy and undergo lactation. They occur in approximately 1% to 2% of women of European descent and 5% to 6% of Asian women. Accessory breast tissue has been classified into eight levels of completeness from a simple patch of hair to a milk-bearing breast in miniature. This classification is based on the presence of glandular and fat tissue, a nipple, an areola, or tufts of hair.

Aberrant mammary tissue in the axilla without nipple formation is more prone to malignant change than is a supernumerary breast, in which the frequency of tumor occurrence is seemingly the same as with a normal single breast. Either benign or malignant tumors can occur in supernumerary or aberrant tissue. A 2000 American Journal of Cardiology article postulated a possible relationship with mitral valve prolapse.

Mammary hypertrophy is a common anomaly of the breast and affects both sexes. In females, the major forms of mammary hypertrophy are precocious or infantile hypertrophy and virginal or gravid hypertrophy occurring, respectively, in adolescent or pregnant women. Precocious mammary hypertrophy is associated with endocrine disturbances of the ovary. It is bilaterally symmetric and rarely of a marked degree. Virginal and gravid hypertrophies are of unknown origin and may be bilateral or unilateral, and the affected breast may grow to enormous size. The enlarging organs are composed of increased amounts of fibrous stroma with hypertrophied ducts, associated at times with lobular formation. The enlargement, once formed, persists. When this type of hypertrophy occurs in teenage girls, it can have a deeply disturbing effect on a teenager's self-image and social development. The only effective treatment is reductive mammoplasty.

Some degree of asymmetry of breast development is common, with roughly 3% of patient examinations notable for asymmetric volume differences relative to the contralateral breast. This asymmetry represented a benign, normal variation unless an associated palpable abnormality is present.

GYNECOMASTIA

Some degree of mammary hypertrophy is normally found in the male breast during adolescence. In two-thirds of all boys between the ages of 14 and 17 years, a button-shaped plaque of mammary tissue is palpated beneath the nipple. This is known as the puberty node. Although gynecomastia is usually bilateral, it can be unilateral. Normally, this involutes before the age of 21. Rarely, this adolescent growth of tissue may be two or three times its normal size and may be persistent. Sometimes it has been found so discrete and firm that the observers classified the enlargement as a benign fibroadenoma. Fat deposition without glandular proliferation is termed pseudogynecomastia.

Gynecomastia most frequently happens in newborn, pubertal, and older males. On palpation, the enlarged mammary gland may be the seat of increased tissue, both mammary and adipose, feeling like the normal female breast. Often a discrete, firm mass is felt, which is composed microscopically of increased amounts of periductal connective tissue surrounding mammary ducts containing hyperplastic epithelium.

Growth of the mammary gland during puberty is explained by changes in the endocrine environment characteristic of this age. Gynecomastia generally results from an imbalance in the estrogen–androgen balance, in favor of estrogen (stimulatory) over androgen (inhibitory), or increased breast sensitivity to a normal circulating estrogen level. Estrogens induce ductal epithelial hyperplasia, ductal elongation and branching, proliferation of the periductal fibroblasts, and an increase in vascularity just as they do in the female breast: the histologic picture is similar in male and female breast tissue after exposure to estrogen. The Leydig cells of the testes, long accepted to be the source of the androgens, also secrete estrogens. Most estrogen production in males is from the peripheral conversion of androgens (testosterone and androstenedione to estradiol and estrone, respectively) through the action of aromatase, mainly in muscle, skin, and adipose tissue. For this reason, overweight adolescent boys are more likely to undergo these changes or to have more marked changes than those of normal weight. The overall prevalence of adolescent gynecomastia ranges from 4% to 69%.

Gynecomastia in late adolescence and in the adult is, in many instances, associated with clinical endocrine disorders that result in estrogen excess or decreased androgens. Any endocrine disorder that results in hypogonadism, either primary, such as Klinefelter syndrome (46, XXY), or secondary, such as hypopituitarism due to an adenoma, can result in gynecomastia. Other causes include testicular and feminizing adrenal neoplasms. Hyperthyroidism is also associated with gynecomastia, which is thought to be related to a relative decrease in circulating free testosterone due to thyroid stimulated increases in sex hormone binding globulin as well as increased peripheral aromatization. Genetic causes of gynecomastia include complete and incomplete forms of androgen insensitivity as well as certain types of congenital adrenal hyperplasia.

Gynecomastia in adult males is often multifactorial. Increased peripheral aromatization of testosterone to estradiol and the gradual decrease of testosterone production in the aging testes probably accounts for gynecomastia in older men. There are a number of medications associated with gynecomastia, including hormones like estrogen, some antibiotics like metronidazole, antihypertensives like spironolactone, antiulcer medications such as ranitidine, and psychoactive drugs like phenothiazines. Alcohol, especially if associated with cirrhosis, marijuana, methadone and amphetamines, has also been associated with gynecomastia.

Rather frequently, gynecomastia is found in patients with testicular tumors (especially chorioepithelioma but also teratoma and interstitial cell tumors). Testicular deficiency in all its forms may be accompanied by gynecomastia of varying degrees. Mammary hypertrophy has been originally described as an integral part of Klinefelter syndrome. Only when the underlying hyalinization process of the tubular apparatus of the testes in this condition starts late in puberty is gynecomastia a frequent but not obligatory phenomenon.

Simple mastectomy, performed through a curved incision following the margin of the areola, remains the most satisfactory treatment.