March et al. lJoint Task Force 11997 |Natlonal surveys of breast core biopsy use Note: Its not within the scope of this survey to include hormonal therapy, chemotherapy, and immunotherapy. History table complied by David A. McClusky ill and John E. Skandalakis. References: Allen JG. Breast. In: Moyer CA, Rhoads JE, Allen JG, Harkins HN (eds). Surgery: Principles and Practice (3rd ed) Philadelphia: JB Lippincott, 1965, pp. 621-661 Ellis H. The treatment of breast cancer: a study in evolution. Ann R Coll Surg Eng 1987;69:212-215. Baum M. Breast cancer 2000 B.C. to 2000 A.D.: tIme for a paradigm shift? Acta Oncol 1993;32:3-8, Figueira-Fo ASS, Salvador-Silva HM, Novals-Dias E. Reconstruction of the breast: types and techniques. In: Figueira: Fo ASS, Salvador-Silva HM, Novals-Dias E, Barros ACSD (eds). Mastology: Breast Diseases. New York: Elsevier, 1995, pp. 367-374. Fisher BF. The revolution in breast cancer surgery: scence or anecdotalism? World J Surg 1985;9:655-666. Forest APM. Lister Oration: Breast cancer: 121 years on. J R Coll Surg Edin 1989;24:239-248, Goldwyn RM. Vincenz Czerny and the beginnings of breast reconstruction. Plast Reconstruct Surg 1978;61:673-681 Lewison EF. The surgical treatment of breast cancer. Surgery 1953;34:904-953, Robinson JO. Treatment of breast cancer through the ages. Am J Surg 1986;151:317-333. Rubin E, Simpson JF. Breast Specimen Radiography. Philadelphia: Lippincott-Raven, 1998. Silverstein MJ. Ductal Carcinoma in Situ of the Breast. Baltimore: Williams & Wilkins, 1997. \Vaeth JM. Historical aspects of tylectomy and radiation therapy in the treatment of cancer of the breast. Front Radiat Ther Oncol 1983;17:1-10. EMBRYOGENESIS OF THE BREAST Normal Development The breast is a group of large glands derived from the epidermis. It lies in a network of fascia derived from the dermis and the superficial fascia of the ventral surface of the thorax. The nipple itself is a local proliferation of the stratum spinosum of the epidermis. During the second month of gestation, two bands of slightly thickened ectoderm appear on the ventral body wall extending from above the axilla to below the groin. These bands are the milk lines and represent potential mammary gland tissue (Fig. 3-1). In humans, only the pectoral portion of these bands will persist and ultimately develop into adult mammary glands. Occasionally, vestigial, or even functional, breast tissue may arise from other portions of the milk line. Fig 3-1.Cgpyyere @2006, by The Mest Hil Companies, Ine Al ichte reser ‘A. The milk lines Ina generalized mammalian embryo. Mammary glands form along these lines. B. Common sites of formation of supernumerary nipples or mammary glands along the course of the miik lines in the human. (From Carlson BM. Human Embryology and Developmental Biology, 2nd ed. St. Louls: Mosby, 1999; with permission.) The glandular portion of the breast develops from the ectoderm, It arises from the local thickening of the epidermis (Fig. 3-2). From this thickening, 16 to 24 buds of ectodermal cells grow into the underlying mesoderm (dermis) during the twelfth week (Fig. 3-28). These buds, at first solid, will become canalized near term to form the lactiferous ducts (Fig. 3-2C). The tips of the buds will give rise to the secretory acini during lactation. The epidermal surface of the future nipple Is at first a shallow pit (Fig. 3-2D). Near term it becomes everted (Fig. 3-2). The areola Is said to be visible from the fifth month onward. Note that an inverted nipple may be a developmental arrest rather than a true pathological condition. Fig 3-2.Epidermis A Mesenehyme B c 0 Nipple E Lactiferous ducts enw: ©2006 by The Mecran-Hil Companies, in Alltighs reser Development of the breast. A-D. Stages in the formation of the duct system and potential glandular tissue trom the epidermis. Connective-tissue septa are derived trom the mesenchyme of the dermis. E. Eversion of the nipple near birth. (Modified trom Skandalakis JE, Gray SW, Rowe JS Jr. Anatomical Complications In General Surgery. New York: McGraw-Hill, 1983; with permission.) ‘The mammary glands form in the same manner as do sweat glands; they are often considered to be modified sweat glands. The areolar glands (of Montgomery) around, but not on the nipple, appear tc be transitional between sweat and lactiferous glands. They serve to lubricate the nipple during lactation (milk production and nursing). The connective-tissue stroma of the breast forms from the mesoderm, which will form the dermis of the skin and the superficial fascia (tela subcutanea) as well, Fibers forming the suspensory ligaments (of Cooper) will develop from both layers. This development, as well as the appearance of fat in the superficial fascia, does not occur until puberty In the female (Fig. 3-3). Fig 3-3.Estrogen Progesterone li stimulation of simulation of duct gronth “ormation of secrelary ven Posterior pituitary (ad Development of the mammary ducts and hormonal control of mammary gland development and function. A. Newborn. B. Young adult. C. Adult. D. Lactating adult. E. Postlactation. (From Carlson BM. Human Embryology and Developmental Biology, 2nd ed. St. Louis: Mosby, 1999; with permission) Although minor changes occur during each menstrual cycle, pregnancy and lactation bring about the ultimate development of the breasts. Progesterone, prolactin, and placental lactogen are key hormones in stimulating the formation of secretory alveoli which develop at the ends of the branched ducts, As development continues, the cells of the secretory alveoli acquire increased organelles related to protein synthesis and secretion During lactation, prolactin from the anterior pituitary gland causes mammary glands to secrete milk proteins and lipids. Milk ejection occurs in response to the neural impulses elicited by sucking activity at the breast. This stimulus causes release of oxytocin by the paraventricular nuclei of the hypothalamus via the posterior pituitary gland. These neural impulses also Inhibit the release of luteinizing hormone. When nursing ceases, prolactin secretion Is reduced. Nonejected milk in the alveoli effects the cessation of milk production. The alveoli regress, and the duct system regresses to the nonpregnant state Firead an Editorial Comment Congenital Anomalies The multiple but rare congenital anomalies of the breast may be associated with various other syndromes. It is not within the scope of this chapter to study these syndromes or their associated anomalies. \elanovich? reviewed the embryology of ectopic breast tissue, supernumerary breasts, and supernumerary nipples in a brief article, and we recommend it to the interested reader.Amastia, Athelia, and Amazia Absence or lack of development of the breast (amastia), or of the areola and nipple only (athelia) is rare, These conditions may be unilateral or bilateral. The corresponding pectoral muscles are often absent as well. There is some indication that the condition Is inherited.> Failure of breast tissue to form when the nipple is present is called amazia Supernumerary Breasts or Nipples Supernumerary breasts or nipples are called accessory if they are on the embryonic milk line, and ectopic if they lie elsewhere. The latter are very rare. Among accessory organs, one can distinguish (1) polymastia, in which there is glandular tissue with or without an areola and a nipple; and (2) polythelia, in which there is a nipple, an areola, or both, but no glandular tissue, as in amazia. It is not always easy to confirm the presence of glandular tissue. Swelling may be produced by subcutaneous fat only (pseudomammae) Among Caucasians, supernumerary mammary structures are thoracic in 90 percent, axillary in S percent, and abdominal in 5 percent. The actual incidence of these structures in the population is between 1 and 5 percent, depending partly on the zeal with which they are sought.+ Discomfort, the risk of neoplasm, and cosmetic considerations are indications for surgical excision of supernumerary mammary structures. Primary breast cancer in aberrant axillary breast tissue was reported by Yerra.> Bailey et al.© reported supernumerary breasts of the vulva and primary mammary carcinoma of the vulva. Congenital Inversion of the Nipple Congenital inversion is a failure of evagination of the nipple. Anomalies of Breast Size In megalomastia, the breast is extremely enlarged. According to Anastassiades and colleagues,” unilateral megalomastia Is extremely rare. However, Netscher et al.® reported massive asymmetric virginal breast hypertrophy in a 13-year-old girl. In micromastia, the breast is very small, failing to develop beyond its prepubertal state. Gynecomastia Gynecomastia refers to enlargement of the male breast. Guvenc et al.? reported on the incidence of pubertal gynecomastia in 646 Turkish boys in Ankara. The highest incidence was at age 14 years (61.1%). The incidence of gynecomastia at various pubertal stages and ages was 34.6%. The incidence of unilateral gynecomastia was 19.6%. A study of healthy young men aged 18-26 found an incidence of 40.5%.2° In a study of 115 men attending a dermatologic clinic, Seibel et al. found an incidence of 27.8% with a skinfold exceeding 2-3 cm and the diameter of the areola greater than 3 cm. Firead an Editorial Comment SURGICAL ANATOMYTopographic Anatomy and Relations Though the terms "mammary gland" and "breast are not synonymous, the latter will be used here for simplicity to indicate both the gland and the associated regional skin, fat, and connective tissues as described hereafter. The adult female breast is located within the superficial fascia of the anterior chest wall. The base of the breast extends from the second rib above to the sixth or seventh rib below, and from the sternal border medially to the midaxillary line laterally. Two-thirds of the base of the breast lies anterior to the pectoralis major muscle; the remainder lies anterior to the serratus anterior muscle. A small par may lie over the aponeurosis of the external oblique muscle.!2 In about 95 percent of women there is a prolongation of the upper lateral quadrant toward the axilla, This tail (of Spence) of breast tssue enters a hiatus (of Langer) in the deep fascia of the medial axillary wall. This is the only breast tissue found normally beneath the deep fascia. Skin The epidermis of the areola and the nipple Is distinguished from that of the surrounding skin by the pink color imparted by blood vessels carried close to the surface in long dermal papillae. In females at puberty, and with each pregnancy, there is an increase in the melanin content of the basal cells, further darkening the area. The dermis of the skin merges with the superficial fascia, which envelop: the parenchyma of the breast. Superficial Fascia The superficial fascia (Fig. 3-4) enveloping the breast is continuous with the superficial abdominal fascia (of Camper) below, and the superficial cervical fascia above. Anteriorly, it merges with the dermis of the skin Fig 3-4.Cervical fascia Clavicle Subclavius muscle Clavipectoral fascia Pectoralis major muscle Intercostal muscle Clavipectoral fascia Pectoralis minor muscle Pectoral fascia Submammary space ‘Superficial fascia Copyright ©2008 by The McGraw-Hill Companies, Ine. All ights reserved Diagrammatic sagittal section through the nonlactating female breast and anterior thoracic wall. Deep FasciaThe deep pectoral fascia envelops the pectoralis major muscle and is continuous with the deep abdominal fascia below. It attaches to the sternum medially and to the clavicle and axillary fascia above and laterally. Along the lateral border of the pectoralis major muscle, the anterior lamina of the deep pectoral fascia unites with the fascia of the pectoralis minor muscle and, more inferiorly, with the fascia of the serratus anterior. A posterior extension of this fascia is continuous with the fascia of the latissimus dorsi and forms the so-called suspensory ligament of the axilla Deep to the pectoralis major muscle, the clavipectoral fascia envelops the pectoralis minor muscle and part of the subclavius muscle and attaches to the inferior aspect of the clavicle, dividing into twc laminae, anterior and posterior to the subclavius (Fig. 3-5). The posterior layer is fused with the fascial anchor of the midportion of the omohyoid muscle and Is connected deeply with the axillary sheath. It extends between the axillary fascia, the clavicle, and the coracoid process. Laterally it unites with the anterior layer of the pectoralis major fascia. Fig 3-5. Copyright ©2008 by The MeGran-HIll Companies, [ne All tights reserved, Parasagittal section through the pectoral region. 1. Trapezius muscle. 2. Cervical investing fascia. 3. Clavicle. 4. ‘Subclavius muscle. 5. Pectoral fascla. 6. Pectoralls major. 7. Axillary sheath. 8. Lateral pectoral nerve. 9. Medialpectoral nerve, entering pectoralis minor muscle. 19. Suspensory ligament of axilla. 11. Latissimus dorsi muscle. 12. Blade of scapula. (Modiied from Colom GL, Skandalakis JE. Clinical Gross Anatomy. Pearl River NY: Parthenon, 1993; with permission.) Laterally, this fascial layer is often thickened as a stout band between the first rib and the coracold process, and Is referred to as the costocoracoid ligament. That part of the fascia between the subclavius and the superior border of the pectoralis minor muscle is sometimes referred to as the costocoracoid membrane. Between the clavicle and the upper edge of the pectoralis minor muscle, this part of the clavipectoral fascia is plerced by the cephalic vein, the thoracoacromial artery and vein, lymphatic vessels and a branch of the lateral pectoral nerve which innervates the clavicular head of the pectoralis major muscle. The axillary fascia lying across the base of the axillary pyramidal space is an extension of the pectoralis major fascia and continues as the fascia of the latissimus dorsi. It forms the dome of the axilla (Fig. 3-64). As noted earlier, the lamina of muscle fascia which interconnects the pectoral musculature and the anterior border of the latissimus dors! is referred to as the suspensory ligamery of the axilla, Occasionally, there is a muscular interconnection within this fascia, which is called the suspensory muscle of the axilla. Fig 3-6.Subslavius, Clavipectoral fascia Pectoralis| major m Aiillarya. Pectoralis ‘minor m. ‘Suspensory Serratus. ligament anterior Deep fascia of armpit (axillary) A Anterior wall C Medial wall Teres major Subscapularis Humerus. Serratus anterior Biceps. Coracobrachilis m, Teres major Skin 3rd rib Pectoralis’ ‘Sternum Latissimus dorsi major m. B Posterior wall D Lateral wail Copyright ©2005 by The Mesrau-tlll Companies, Tne. Allah reserved Diagram of the walls of the axilla. (Skandalakis JE, Skandalakis PN, Skandalakis LJ. Surgical Anatomy and Technique: A Pocket Manual, 2nd Ed. New York: Springer-Verlag, 2000; moaified by permission of Basmalian JV, Slonecker CE. Grant's Method of Anatomy, 1 1th Ed. Baltimore: Williams & Wilkins, 1989.) ‘The prevertebral fascia gives off a sheet that covers the floor of the posterior triangle of the neck Where the axillary vessels and the nerves to the arm pass through the fascia, they take with them a tubular fascial sleeve, the axillary sheath. The axillary vessels and the nerves to the arm pass through the sheet and floor, and take with them a tubular fascial sleeve, the axillary sheath. The clavipectoral fascia can be thought of as consisting of five parts (Fig. 3-6) » The attachment to the clavicle and the envelope of the subclavius muscle + That part between the subclavius and pectoralls minor muscles, referred to by some as the "costocoracold membrane" + The thickened lateral band between the first rib and the coracoid process, the costocoracoid ligament+ The pectoralls minor envelope «The suspensory ligament of the axilla attaching to the axillary fascla. Axilla The axilla is defined as a pyramidal space having an apex, a base, and four walls. The apex is a triangular space bordered by the clavicle, the upper border of the scapula, and the first rib, which is sometimes called the cervicoaxillary canal. The base consists of the axillary fascia beneath the skin of the axillary fossa. The anterior wall is composed of three muscles (the pectoralis major, the pectoralis minor, and the subclavius) and the clavipectoral fascia, which envelops the muscles and fills the spaces between them (Fig. 3-6A). The posterior wall is formed by the scapula and three muscles: the subscapularis, the latissimus dorsi, and the teres major (Fig. 3-68). The medial wall consists of the lateral chest wall, with the second to sixth ribs, and the serratus anterior muscle (Fig 3-6C). The lateral wall Is the narrowest of the walls, being formed by the bicipital groove of the humerus (Fig. 3-6D). Firead an Editorial Comment The axilla contains lymph nodes (about which more will be said later in this chapter); the axillary sheath (which covers blood vessels and nerves); and the tendons of the long and short heads of the biceps brachii muscle and the coracobrachialis muscle (Fig. 3-7) Fig 3-7.Thoracoacromial a pillar a (axillary v.not shown) Lateral pectoral n. Biceps (short) m. Coracobrachialis m. Pectoralis minor Lateral thoracie a Pectoralis major Subscapularis m. wubscapularis m. Medial pectoral n Thoracodorsal n Latissimus dorsi m Serratus anterior m.. Long thoracic n. Copynght @2006 py The Mesraw-Hil Companiae. Ins Allnighis vesersad Topography of the axilla. Anterior view. (Modiied trom Skandalakis JE, Gray SW, Rowe JS Jr. Anatomical Complications in General Surgery. New York: McGraw-Hill, 1983; with permission) A Read an Editori Muscles ‘The muscles and nerves with which the surgeon must be familiar are listed in Table 3-2. However, the surgeon should also be familiar with their related fasciae and with the topography of the blood vessels Table 3-2. Muscles and Nerves Involved in Mastectomy Muscle (origin Insertion epply Comments. Pectoralis Medial half of clavicle, —_|Laterallip, __|Lateraland _|Ciavicular portion of pectoralls forms upper major lateral hait of sternum, 2nd |picipital Imedial lextent of radical mastectomy; lateral border ito 6th costalcartllages, _fgroove lpectoral ltorms medial boundary of modified radicallaponeurosis of external nerves mastectomy; both nerves should be loblique muscle preserved in modified radical procedure Pectoralis [2°10 57 ribs [Coracoid —_|Lateral and minor lprocess ot medial lscapula pectoral nerves Dettoid [Lateralhalfofciavicle, _ |Deltold [axillary nerve lateral border of acromion tuberosity of process, spine of scapula _[numerus Serratus 1. 1Sand 2¢ribs [Costal surface|Long thoracic [injury produces "winged scapula” lanterior (3 jot scapula at {nerve parts) |superior angle 2. 20d to at ribs \Vertebral lborder of [scapula [3.410 at ribs [Costal surface jot scapula at inferior angle Latissimus |Back, tocrestotiium _ |Crest of lesser| Thoracodorsail The anterior border forms the lateral extent ldors! jubercle and |nerve lot radical mastectomy; injury resutts In intertubercular hweakness of rotation and abduction of arm Igroove of humerus [Subclavius [Junctionof 1stribandits [Groove ot |Subclavian (cartilage lower surface |nerve jot clavicle /Subscapularis|Coslal surface of scapula |Lesser lUpperand — |Subscapular nerves should be spared tubercle ot flower lhumerus subscapular nerves Exemal [External oblique muscle [Recius sheath Remember the interdigitation with serratus loblique land linea alba, lanterior and pectoralis muscles laponeurosis rest of Ilium Rectus Ventral surface of Sto |Crestand [Branches of |The rectus sheath Is the lower limit of Jabdominis [7m costal cartilages and |superior ——_|7th-12t radical mastectomy ixiphold process ramus of thoracic pubis nerves ‘Source: Skandalakis JE, Gray SW, Rowe JS Jr. Anatomical Complications in General Surgery. New York: McGraw- Hill, 1983; with permission. Morphology Each breast is composed of between 15 and 20 lobes, some larger than others, within the superficia fascia, which is loosely connected with the deep fascia. These lobes, together with their ducts, are anatomic units, but not surgical units. A breast biopsy is not a lobectomy; In such a procedure, part: of one or more lobes are removed. Between the superficial and deep fasciae is the retromammary (submammary) space, which is rich in lymphatics (Fig. 3-8, Fig. 3-4). This space was at one time used for submammary infusions when the venous route was not used Fig 3-8.Cgpuyare @2006 09 The Mecraw Hil Companis, Inc Al ichis reserve The retromammary space. 1. Membranous layer of superficial fascla. 2. Retromammary space. 3. Muscle fascia. (Moaiied from Colborn GL, Skandalakis JE. Clinical Gross Anatomy. Pearl River NY: Parthenon, 1993; with permission.) ‘The lobes of parenchyma and their ducts are arranged radially with respect to the position of the nipple, so that the ducts pass centrally toward the nipple like spokes of a wheel and terminate separately upon the summit of the nipple. The segment of the duct within the nipple is the narrowest portion of the duct. Therefore, secretions or sloughed cells tend to collect within the part of the duct just deep to the nipple, resulting in apparent expansion of the ducts which, when dilated by their contents, are called lactiferous sinuses (Fig. 3-9) Copyright ©2008 by The McGraw-Hill Companies, Inc. All igh's reserved Breast topography. From a dissection photograph. 1. Retinacula cutis. 2. Membranous layer. 3. Serratus anterior fascia. 4, Serratus anterior muscle. 5. Pectoral fascia. 6. Pectoralis major muscle. 7. Suspensory ligament of axilla. Lobe of breast parenchyma. 9. Lactiferous duct. 19. Ampulla. (Modified from Colborn GL, Skandalakis JE. Clinical Gross Anatomy. Pearl River NY: Parthenon, 1993; with permission.) In the fat-free area under the areola, the dilated portions of the lactiferous ducts (the lactiferoussinuses) are the only sites of actual milk storage. Intraductal papillomas may develop here. The ducts are surrounded by a sheath of soft, cellular, intralobular connective tissue derived from the upper papillary layer of the dermis. Between the ducts Is the denser, less cellular connective tssue from the reticular layer of the dermis. Because of the radial arrangement of the lobes with respect tc the nipple, the site of production of serous or sanguinous fluid emerging upon the surface of the nipple can be determined by stroking the breast tissue with the tip of a finger, beginning peripherally and terminating at the nipple The suspensory ligaments of Cooper form a network of strong, irregularly-shaped connective-tissue strands or bands connecting the dermis of the skin with the deep layer of superficial fascia, passing between the lobes of parenchyma and attaching to the parenchymal elements and ducts Occasionally, the superficial fascia Is fixed to the skin in such a way that ideal subcutaneous total mastectomy is impossible Firead an Editor: With malignant invasion, portions of the ligaments of Cooper may contract, producing a characteristic fixation and retraction or dimpling of the skin (Fig. 3-10). This must not be confused with the irregular, roughened appearance of the skin called peau d'orange, which Is secondary to obstruction of the superficial subcuticular lymphatic vessels. In peau d'orange, the subdermal attachment of hair follicles and the edematous skin results in the pitted appearance of the skin Comment Fig 3-10. Copyright ©2008 by The McGraw-Hill Companies, Ine. All ights reserved, Dimpling of the breast, resulting from involvement of Cooper's ligaments by invasive disease. The dimpling Is ‘emphasized by the pressure of the hand of the examiner. From a clinical photograph. (Modified trom Colborn GL, ‘Skandalakis JE. Clinical Gross Anatomy. Pearl River NY: Parthenon, 1993; with permission.) In the resting (nonlactating) breast, the main duct system is present, but there are few or nosecretory acini. During pregnancy, the ducts proliferate, and secretory acini develop at the ends of each of the smaller branches. The intralobular connective tissue becomes thinned to form well- vascularized septa separating adjacent acini. Although there is a relative reduction in the quantity of adipose tissue present, there is an increase in the size of the breast because of duct and acinus formation Blood Supply Arterial Supply With considerable variation, the breast is supplied with blood from three sources: the internal thoracic artery, branches of the axillary artery, and the intercostal arteries (Fig. 3-7, Fig. 3-11). Fig 3-11.A18% Axillary artery Internal thoracic arte B30% Intercostal arteries, Branches of intemal thoracic arta i oc C 50% Intercostal arteries, wwillary artery a Branches of internal thoracic artery copyright 92008 by The Mesrav-vill Companies, Inc All ights reserved,‘A. The breast may be supplied with blood from the internal thoracic, the axillary, and the intercostal arteries In 18 percent of individuals. B. In 30 percent, the contribution from the axillary artery Is negligible. C. In 50 percent, the Intercostal arteries contribute little or no blood to the breast. In the remaining 2 percent, other variations may be found. (Modified trom Skandalakis JE, Gray SW, Rowe JS Jr. Anatomical Complications in General Surgery. New York: McGraw-Hill, 1983; with permission.) INTERNAL THORACIC ARTERY The internal thoracic branches supply most of the blood to the breast. The internal thoracic (or internal mammary) artery Is a branch of the subclavian artery; it courses parallel with the lateral border of the sternum behind the transversus thoracis muscles. From the internal thoracic artery, perforating branches pass through the intercostal muscles of the first six interspaces and the pectoralis major muscle to supply the medial half of the breast and surrounding skin. The mammary rami of the first two of these perforating branches are the largest, although in some cases, the first and third or second and fourth are the largest. Typically these arteries descend laterally toward the nipple-areolar complex so that most of the arterial supply arises above the level of the nipple (Fig. 3-12). Therefore, radial incisions in the upper half of the breast are less likely to injure the major arterial supply than transverse incisions. We agree with Morehead! that the inferior parts of the breast below the level of the nipple are almost free of major vessels. Fig 3-12. Copyright ©2008 by The MeGray-HIll Companies, Ine All tights reserved, Blood supply of the breast; drawing from a dissection photograph. The arterial supply Is here derived chietly trom (A) direct mammary branches of the axillary artery; (B) branches of the lateral thoracic artery; (C) perforating branches of the internal thoracle artery. The venous drainage is comparable, and Is illustrated on the right side of the drawing The rib levels are Indicated by numbers. (Modified from Colborn GL, Skandalakis JE. Clinical Gross Anatomy. Pear! River NY: Parthenon, 1993; with permission.) BRANCHES OF THE AXILLARY ARTERYFour branches of the axillary artery may supply the breast. They are, in order of appearance, (1) the supreme thoracic branch, (2) the pectoral branches of the thoracoacromial artery, (3) the lateral thoracic arteries, and (4) unnamed mammary branches. The lateral thoracic artery is the most Important of these vessels. The axillary vasculature supplies the lateral portion of the breast. INTERCOSTAL ARTERIES The lateral half of the breast may also receive branches of the third, fourth, and fifth intercostal arteries. Only about 18 percent of breasts are supplied by all three of these sources.14 only the branches from the internal thoracic artery are always present to some degree (Fig. 3-11). In most breasts, there are free anastomoses between the arteries supplying the breast; occasionally all three arterial sources remain separate.14 Venous Drainage The axillary, internal thoracic, and the third to fifth intercostal veins drain the mammary gland. These veins follow the arteries (Fig. 3-12) The perforating tributaries from the medial half of the breast carry the greater part of the venous drainage. They enter the internal thoracic vein, which joins the brachiocephalic vein. The axillary vein is formed by the junction of the basilic and brachial veins. It lies medial or superficial to the axillary artery and receives one or two pectoral branches from the breast. As it crosses the lateral border of the first rib, the axillary vein becomes the subclavian vein. The intercostal veins communicate posteriorly with the vertebral venous system, which enters the azygos, hemiazygos, and accessory hemiazygos veins, which in turn drain to the superior vena cava Anteriorly, they communicate with the brachiocephalic vein by way of the internal thoracic veins. By the first two pathways, metastases of the breast readily reach the lungs. By the third pathway, metastases may travel to the skeleton and the central nervous system (Fig. 3-13). Fig 3-13.Aint thoracic v. to rightieart & lungs i brs of axillary. to right Peart & lungs C.Intercostalv tosup. epigastric w. & liver (at umbilicus) Cgpyyare @2026 07 Me Mes Hil Compania, In Al iches reser Diagram of a frontal section through the right breast showing pathways of venous drainage. A. Medial drainage through internal thoracic vein to the right heart. B. Posterior drainage to vertebral veins. C. Lateral drainage to intercostal, superior epigastric veins, and liver. D. Lateral superior drainage through axillary vein to the right heart. (Moaiied from Skandalakis JE, Gray SW, Rowe JS Jr. Anatomical Complications in General Surgery. New York: McGraw-Hill, 1983; with permission.) ‘There are several places in the body where communication exists between the systemic and the portal venous systems. With obstruction of the portal vein, these communications may permit portal blood to enter the systemic veins. Even in the absence of portal obstruction, there Is no reason why systemic blood might not enter the portal system. One such location is the lower esophagus. It is drained by anastomosing tributaries of the azygos (systemic) vein and tibutaries of the left gastric (portal) vein. Another such site is in the region of the navel, where there are anastomoses between small veins of the portal system, which pass from the umbilicus to the liver through the falciform ligament, and the epigastric veins, which also drain the umbilical region into the internal thoracic veins. Through one or more of these portocaval anastomoses, metastatic cells from the breast may reach the liver. Firead an Editorial Comment Lymphatic Drainage Lymph nodes of the breast region occur in inconstant groups of varying numbers. This inconstancy |: mirrored, if not magnified, by the terminology presented by different authors. We find the terminology of Haagensen!® most useful. Keep in mind that the lymph nodes are not neatly grouped, and that many nodes are very small (Fig. 3-14). Only the most careful search of the pathologic specimen will reveal all the lymph nodes present. Fig 3-14,Subclavicular nodes ilar vein nodes Interpectoral Extemal mammary nodes nodes Copyright ©2008 by The McGraw-Hill Companies, Ine. All ighis reserved Lymph nodes of the breast and axilla. Classitication of Haagensen. (Moditied from Skandalakis JE, Gray SW, Rowe JS Jr. Anatomical Complications in General Surgery. New York: McGraw-Hill, 1983; with permission.) ‘The major groups of Haagensen! are 1) axillary, and 2) internal thoracic (mammary). The average number of nodes in each group follows. Axillary Drainage (35.3 Nodes) Group 1. External mammary nodes (1.7 nodes), also called the anterior pectoral nodes. These lie along the lateral edge of the pectoralis minor, deep to the pectoralis major muscle, along the medial side of the axilla following the course of the lateral thoracic artery on the chest wall from the second to the sixth rib (Fig. 3-15). Deep to the areola there is an extensive network of lymphatic vessels, the so-called subareolar plexus of Sappey. In the circumareolar region, large lateral and medial trunks receive much of the lymph from the breast parenchyma. The lateral trunk receives collateral from the upper half of the breast and the internal trunk drains the lower part of the breast. These vessels pass around the lateral border of the pectoralis major muscle to reach the external mammary nodes. Ess‘Sprache @z03¢ by The MeGraw-Htl Companies, In Lymphatic drainage of the breast. Direction of lymph flow trom skin Indicated by arrows on right breast and medial side of left breast. 1. Areolar plexus of vessels, draining areola, nipple and some parenchyma. 2. Anterior pectoral nodes. 3. Central axillary nodes. 4. Interpectoral nodes (a path which can bypass central axillary nodes). 5. Apical, infraclavicular nodes. 6. Retrosternal nodes. (Modified trom Colborn GL, Skandalakis JE. Clinical Gross Anatomy. Pearl River NY: Parthenon, 1993; with permission.) Group 2. Scapular nodes (5.8 nodes). These lie on the subscapular vessels and their thoracodorsal branches. Lymphatics from these intercommunicate with intercostal lymphatic vessels. Group 3. Central nodes (12.1 nodes). This is the largest group of lymph nodes; they are the nodes most easily palpated in the axilla, because they are generally larger in size. They are embedded in fat in the center of the axilla, When these nodes enlarge, they can compress the intercostobrachial nerve, the lateral cutaneous branch of the second or third thoracic nerve, causing accompanying pain. Group 4. Interpectoral nodes (Rotter's nodes) (1.4 nodes). These lie between the pectoralis major and minor muscles. Often there is a single node. They are the smallest group of axillary nodes and will not be found unless the pectoralis major is removed. Group 5. Axillary vein nodes (10.7 nodes). This Is the second largest group of lymph nodes in the axilla. They lie on the caudal and ventral surfaces of the lateral part of the axillary vein, Group 6. Subclavicular nodes (3.5 nodes). These lie on the caudal and ventral surfaces of the media part of the axillary vein. Haagensen?5 considered them to be inaccessible unless the pectoralis minor muscle is sacrificed. Internal Thora (Mammary) Drainage (8.5 Nodes)Lymphatic vessels emerge from the medial edge of the breast on the pectoralis fascla. They accompany the perforating blood vessels, which, at the end of the intercostal space, plerce the pectoralis major and intercostal muscles to reach the internal thoracic nodes. These nodes also receive lymphatic trunks from the skin of the opposite breast, the liver, the diaphragm, the rectus sheath, and the upper part of the rectus abdominis.15 The nodes, about four to five on each side, are small and are usually In the fat and connective tissue of the intercostal spaces. The internal thoracic trunks empty into the thoracic duct or the right lymphatic duct. This route to the venous system Is shorter than the axillary route Since dissection of the internal mammary nodes is not done today, Scatarige et al.1© advised lateral chest radiography, computed tomography, high-resolution sonography, magnetic resonance imaging and radionuclide lymphoscintigraphy. Firead an Editorial Comment Winer et al.27 expanded the regional lymph node terminology to include a transpectoral route in the axillary group. We present their classification verbatim. The breast lymphatics drain by way of three major routes: axillary, transpectoral, and internal mammary. Intramammary lymph nodes are considered with, and coded as, axillary lymph nodes for staging purposes; metastasis to any other lymph node is considered distant (M1), including supraclavicular, cervical, or contralateral internal mammary. The regional lymph. nodes are presented here! 1. Axillary (ipsilateral): interpectoral (Rotter's) nodes and lymph nodes along the axillary vein and its tributaries that may be (but are not required to be) divided into the following levels: a. Level I (low axilla): lymph nodes lateral to the lateral border of the pectoralis minor muscle b. Level II (midaxilla): lymph nodes between the medial and lateral borders of the pectoralis minor muscle and the interpectoral (Rotter's) lymph nodes c. Level III (apical axillary): lymph nodes medial to the medial margin of the pectoralis minor muscle including those designated as subclavicular, infraclavicular, or apical Note: Intramammary lymph nodes are coded as axillary lymph nodes. 2. Internal mammary (ipsilateral): lymph nodes in the intercostal spaces along the edge of the sternum in the endothoracic fascia Any other lymph node metastasis is coded as a distant metastasis (M1), including supraclavicular, cervical, or contralateral internal mammary lymph nodes. Arrangement of Lymph Nodes and Metastasis The spread of malignancy of the breast is via a hematogenous route, via the lymphatics, and through local infiltration. From a purely surgical standpoint, the axillary lymph nodes can be divided into 3 levels Level I: lateral to the lateral border of the pectoralis minor muscle Level II: under the pectoralis minor muscle Level III: medial to the medial border of the pectoralis minor muscleSome authors have stated that regional lymph nodes are primary indicators and not instigators of distal disease. They advise that lower axillary dissection is more than adequate to fulfill the aims of the operation. These authors believe that with removal of a few lymph nodes, the qualitative axillary node status (positive or negative) can be determined with accuracy. We quote from Brand et al. 28: The nearly identical patterns of treatment failure in lymph node negative and positive breast cancer patients suggest that metastasis in node negative patients occurs by a similar mechanism. The shorter time to recurrence and larger primary tumor may only reflect a lead time bias, in that node-positive patients have a greater tumor burden in their lymph nodes that facilitates identification by pathologists. The pathway of metastasis follows the direction of lymph flow to the lymph nodes (I, then to II and mn. However, Veronesi et al.19 reported that with a tumor mass measuring up to 2 cm, metastasis to lymph nodes of level I was 69.9%, to levels I and II was 13.2%, and to all levels was 11.3%. Robinson et al.2° reported skip metastasis to levels II and III in 5.6% of cases. In general, the lymphatic drainage of the breast accompanies the blood supply. Hultborn and colleagues?! concluded that drainage from any quadrant of the breast passes to axillary nodes (75 percent) and to the internal mammary chain (25 percent). Haagensen? traced lymph flow upward and laterally through the tail of the breast to the central lymph nodes (Fig. 3-16). It is here that metastases are most frequently found. Another drainage path is by way of lymphatics that pierce the pectoralis major muscle and pass upward between the pectoralis major and minor muscles to reach the axillary vein group or the subclavicular group of nodes. Between the two muscles there may be a few interpectoral nodes (of Rotter). Lymphatics from these nodes may bypass the central axillary group and drain directly to subclavicular nodes. The subclavicular group of nodes is important, since Haagensen!® believed that metastasis to these nodes renders a surgical cure impossible Fig 3-16.Subclavicular (apical) nodes ae Nrillary nodes Central nodes Interpectoral (Rotter) nodes int. mammary (parasternal, mediastinal) nes — 25% Scapular nodes { Ext. mammary (pectoral) nodes Copyright ©2096 by The McGraw-Hill Companies, Inc AI NGH reserved Diagram of lymphatic drainage of the breast. (Modified trom Skandalakls JE, Gray SW, Rowe JS Jr. Anatomical Complications in General Surgery. New York: McGraw-Hill, 1983; with permission) Read an Editorial Comment Innervation (Fig. 3-17, Fig. 3-18) Sarhadi et al.22 stated that their findings". . are uncannily like those of Cooper23 who described the nerves supplying the breast as arising from the 2nd-6th intercostal nerves, with mammary branches passing on the surface of the gland and intercommunicating. He [Cooper] also described the two mammary branches from the 4th lateral cutaneous nerve and mentioned that the nipple receives its innervation through a plexus under it." Fig 3-17.‘Thoracodorsal n. Copyright ©2008 by The McGraw-Hill Companies, Inc All ights reserved Diagrammatic representation of Important peripheral nerves encountered during mastectomy. (Modified from Aitken DR, Minton JP. Complications associated with mastectomy. Surg Clin North Am 1983;63:1331-1352; with permission)Dorsal scapular nerve To phrenic nerve From C4 cs To scaleni Suprascapular nerve Nerve to subolavius. co Lateral pectoral nerve Toscaleni cr Lateral cord Toscaleni Long thoracic nerve ca Posterior cord Toscaleni u Musculocutaneous nerve ‘villary nerve Radial nerve From 12 First intercostal nerve Median nerve ‘Medial pectoral nerve ‘Thoracodorsal Upper subscapular newve nerve Ulnar nerve Medial cord Lower subscapular nerve Medial cutaneous Medial cutaneous nerve of forearm nerve of arm Cosysight #2006 by The Media Hill Commpeniag, ne Ab vigite veveren ‘A planof the brachial plexus. The posterior division of the trunks and their derivatives are shaded. The tibers trom C7 which enter the ulnar nerve are shownas a heavy black line. Letters and numbers C4-C8 and T1-T2 indicate the ventral rami of these cervical and thoracic spinal nerves. (Modified from Williams PL (ed). Gray's Anatomy (38th ed). New York: Churchill Livingstone, 1995; with permission) Thoracodorsal Nerve The thoracodorsal nerve (middle subscapular) arises deeply from the posterior cord of the brachial plexus, ventral to the subscapularis muscle (Fig. 3-19); it passes downward and medially to reach and innervate the latissimus dorsi muscle. Feller and Woodburne?¢ stated that the nerve and its associated vessels can best be found near the medial border of the latissimus dorsi about 5 cm above a plane passing through the third sternochondral junction, Once located, the neurovascular bundle should be marked with umbilical tape for protection. If there Is obvious involvement of lympr nodes around the nerve, it must be sacrificed. Fig 3-19.Upper subscapular n, willayy. Long thoracic n Pectoralis major & Thoracodorsal a. minor (cut) Sudscapularis m. Serratus anterior m. Medial border of latissimus dorsi m Copyright @2008 by The McGraw-Hill Companies, Ine All tights reserved, The triangular bed of an axillary dissection. (Modified trom Skandalakis LJ, Vohman MD, Skandalakis JE, Gray SW. ‘The axillary lymph nodes in radical and moalied radical mastectomy. Am Surg 1979;45:552; with permission.) Long Thoracic Nerve The long thoracic nerve innervates the serratus anterior muscle and lies on it (Fig. 3-19). When the superficial fascia is reflected, the nerve or branches from It can be reflected also, making identification of the nerve difficult. Unless actually invaded by cancer, this nerve should be spared to avoid "winging" of the inferior angle of the scapula. The landmark for locating the nerve is the point at which the axillary vein passes over the second rib. Careful dissection of this area will reveal the nerve descending on the second rib posterior to the axillary vein.2+ Anterior Thoracic Nerves (Pectoral) The importance of the medial and lateral pectoral (anterior thoracic) nerves was emphasized by Scanlon and Caprini,25 Moosman,2® and Scanlon.27 The medial pectoral nerve is superficial to the axillary vein and lateral to the pectoralis minor muscle. The lateral pectoral nerve, which is larger than the medial nerve, Is the nerve supply of the clavicular part of the muscle as well as the sternal portions of the pectoralis major muscle. It is also superficial to the axillary vein and lies at the medial edge of the pectoralis minor muscle. The branch of the lateral pectoral nerve to the clavicular head of the pectoralis major muscle arises proximal to, or beneath, the clavicle The medial pectoral nerve arises from the medial cord of the brachial plexus near the origin of the thoracoacromial artery from the axillary artery. The lower part of the lateral pectoral nerve crosses the axillary artery just distal to the origin of the thoracoacromial artery and joins the medial pectora nerve, forming a neural loop of varying size. From this loop, several branches arise which pass into the pectoralis minor muscle, some penetrating that muscle to enter the overlying pectoralis major muscle. Such branches supply the sternal and costal parts of the pectoralis major muscle. Intercostobrachial NerveThe intercostobrachial nerve is the lateral cutaneous branch of the 2nd or 3rd intercostal nerve, or a combination of the two intercostal nerves. After crossing the fatty and lymphatic tissues of the axilla posteromedially, it reaches the medial area of the skin of the arm. Usually, this nerve Is sacrificed. Firead an Editorial Comment HISTOLOGY AND PHYSIOLOGY The majority of the material presented here is based on Ham's Histology2® and Gray's Anatomy.29 Breasts (Mammary Glands) There are approximately 20 individual compound alveolar glands in each breast. Independent ducts open onto the surface through the nipple. Arudimentary duct system is present at birth, and remains in that state until the onset of puberty in females. At puberty, the breasts enlarge and become more rounded. The nipples become more prominent. Growth is largely due to increased fat between the lobes and the lobules. There is some development of the duct system, but secretory structures develop only in response to pregnancy. A-small amount of breast tissue develops in 50% of adolescent boys but usually regresses after approximately one year. An approximately similar incidence of this phenomenon is seen In old men. Estrogen affects breast development in both males and females, physiologically and pathologically. Pregnancy brings about the addition of progesterone, which affects the development of secretory alveoli. Prolactin and chorionic somatomammotrophin complete the development of the secretory alveoli. Glucocorticoids, growth hormone, thyroid hormone, and insulin are also present during pregnancy. Nipples (Fig. 3-20) The nipple, which is well innervated by the 4th intercostal nerve, Is surrounded by the areola, The pigmentation of the areola increases with pregnancy. Within the nipple and areola are some dermal papillae, and a very thin epithelium Fig 3-20.Lactiferous duct Smooth muscle Copyright @2008 by The MeGran-HIll Companies, Ine All tights reserved, Photomicrograph of a section of a nipple, cut perpendicular to the skin surface (very low power). (Modified from Cormack DC. Ham's Histology (3th ed). Philadelphia: JB Lippincott, 1987; with permission.) Approximately 20 ducts open onto the surface of each nipple. The main ducts are called the lactiferous ducts. Stratified squamous keratinizing cells make up the epithelium of the ducts near their surface. Deeper in the ducts, the epithelium becomes a double layer of columnar cells, Smooth muscle is embedded within the dense connective tissue which supports the parenchymatous tissue. Some muscle Is oriented circularly around the ducts; other muscle Is longitudinally parallel with the ducts. Lactiferous sinuses are the dilated terminal portions of the lactiferous ducts, capable of storing milk during milk ejection. Due to loss of the placenta at birth, nipples can suffer from estrogen deficiency for a transient perioc until the ovaries increase hormone production Resting Breast (Fig. 3-21) The resting breast is defined as a postpubertal breast in an inactive state, not stimulatec to become secretory by adequate hormone levels. The lactiferous sinus constitutes a lobe, with numerous lobules per lobe. It develops as a downgrowth of surface epithelium. Growth continues through the dermal papillary layer and into the reticular layer as the duct system is formed Fig 3-21.Epidermis Papillary layer of dermis, Reticular layer of dermis Intralobular connective tissue derived by downgrowth of papillary layer of dermis Interlobular connective tissue containing regions of adipose tissue Ducts Copyright ©2008 by The MeGran-Hill Companies, [ne All tights reserved, ‘Schematic diagram of the organization of the resting breast, Illustrating how its intralobular connective tissue corresponds to the papillary layer of the dermis. Extensions of the reticular layer of dermis constitute interlobular suspensory ligaments and septa. (Modified from Cormack DC. Ham's Histology (Sth ed). Philadelphia: JB Lippincott, 1987; with permission.) Dermis Ussue surrounding the duct system Is more cellular than in typical dermis and becomes the intralobular connective tissue. Less cellular dermis forms a coarser tissue which separates the lobules; itis thus interlobular connective tissue, with regions of adipose tissue contained within it. Some of the larger of these interlobular support structures form the suspensory ligaments (of Cooper). Intralobular ducts are lined with cuboidal epithelium: narrower ones have a simple cuboidal epithelium, larger ones a double layer of cuboldal epithelium. Lactation (Fig. 3-22) With pregnancy, the duct system completes its development. Many intralobular ducts form extensively during the proliferative phase. Secretory alveoli form at the tip of the smallest intralobular ducts and complete the lobules. Each secretory alveolus forms a small cul de sac (secretory lobule) lined with columnar epithelium. Myoepithelial cells are related to the basal side of each secretory alveolus. Fig 3-22.Interlabula septa (fibrous) conan @2006 ty The Mesian Hil Corpor, ie Photomicrograph of fully developing breast. This tissue was obtained during the fifth month of pregnancy, when the secretory changes associated with lactation become manifest. Alveoll at upper right are distended with colostrum; many of those at bottom right have not yet begun to secrete. (Modified trom Cormack DC. Ham's Histology (3th ed), Philadelphia: JB Lippincott, 1987; with permission.) The secretory phase is brought on by changed levels of progesterone, lactogenic hormones (maternal and placental), and estrogen. Colostrum is secreted during the third trimester, milk shortly after birth. Not all lobules secrete at the same level. Therefore, under the microscope some lobules are distended, others are not. Interlobular partitions of connective tissue become considerably thinned as the secretory portions of the breast become more active and enlarged. Secretory cells produce numerous lipid droplets of widely varying sizes. While intracellular, lipid droplets are not surrounded by a membrane, but during exocytosis, they become enwrapped by cell membrane. Electron-dense secretory granules containing milk proteins also are found in secretory cells. These, too, undergo exocytosis. Columnar cells with sparse populations of microvilli are another component of secretory lobules. Milk Ejection Milk ejection occurs only during nursing. The sucking stimulation of the breast sends neural impulse: to the hypothalamus. The hypothalamus stimulates oxytocin secretion by paraventricular nucle! cells, and suppresses the release of prolactin-inhibiting hormone (PIH). Oxytocin stimulates myoepithelial cells of secretory alveoli of the breast, effecting milk passage through the lactiferous ducts. Prolactin secretion is maintained when the PIH Is suppressed and lactation continues. Regression of Breast Tissue During regression of breast tissue, alveoli disappear and lobules greatly reduce in size. Partitions formed by connective tissue become thicker again.‘At menopause the estrogen level falls, resulting in atrophy of stroma and parenchymal elements. Changes Include Irregular growth and some secretory fluctuation; some ducts proliferate, while others may secrete and form cysts SURGICAL APPLICATIONS There are several types of mastectomy, distinguished by the extent of axillary dissection. Radical mastectomy involves removal of the breast and axillary lymph nodes, as well as the pectoralis major and minor muscles and the fascia. Modified radical mastectomy involves removal of the breast and axillary lymph nodes, preserving the pectoralis muscles. Simple, or total, mastectomy involves removal of the breast only. Lumpectomy or removal of a small malignant tumor can be performed in combination with axillary node dissection. Excisional biopsy involves removal of a small tumor, perhaps not palpable, with a rim of healthy breast ssue around it Peralta et al.3° found that contralateral prophylactic mastectomy prevented contralateral breast cancer, prolonging both disease-free survival and overall survival. Our late friend John Bostwick?! stated: Today, women diagnosed with breast cancer have more and better options for treatment, preservation, and reconstruction of the breast. The breast management team epitomizes the optimal care now available to women with immediate breast reconstruction. Patient education and added value placed on this important part of the care of the woman with breast cancer are needed so that more women can have breast cancer treatment and still have a breast. Another procedure, for very small multiple tumors detected by mammography, is subcutaneous mastectomy, in which the glandular tissue is excised, but the skin of the breast is preserved. However, this is controversial. In many patients, some peripheral glandular tissue will be overlooked.32 The pectoral fascia must be removed in order to extirpate deep mammary tissue Frequent follow-up examinations are mandatory.33 Park et al.34 support the use of stereotactic large-core needle breast biopsies as a diagnostic procedure for suspicious lesions. D'Angelo et al.35 also support stereotactic excisional breast biopsy for nonpalpable mammographic breast lesions. Lanstberg et al.,3& who consider mammography the “gold standard for breast imaging and early detection of breast cancer, also found wire-guided surgical breast biopsy "accurate and successful. . . for diagnosing pathology at the price of invasive technique. Early detection and treatment leads to improved survival and less disfiguring treatments." Wellman et al.37 advocated the use of the imaging modality, tactile imaging, to estimate the size of breast masses, enhancing cancer surveillance for patients with benign masses due to fibrocystic changes or scarring. Meyer et al.38 advised that in suspicious nonpalpable breast abnormalities, image-guided large-core needle biopsy is a reliable diagnostic alternaltive to surgical excision. Smith et al.39 found ultrasound an effective technique for localizing and excising nonpalpable lesions. However, Dent,49 in a review of axillary lymphadenectomy for breast cancer, stated, "The criterion standard of assessing axillary lymph node involvement is stil full histological assessment.” He concluded: "During the course of a mastectomy, if glands are palpable (or selected glands are positive on frozen section or on contact cytology) axillary clearance could be undertaken."Winchester et al.41 reported the anatomic subsite (distribution) of lobular and ductal carcinoma of the breast in Table 3-3. Table 3-3. Distribution of Tumor Location According to Histology, All Patients| Location [Lobutar (%) [Ductal (7) [Combination (%) Nipple 2 7 1.9 (Central [6.0 [53 61 [Upper inner 73 [a2 a3 Lower inner [3.8 [a7 39 [Upper outer [37.0 [36.9 374 Lower outer [58 lea 57 [axillary tall foe los (06 [Overiapping™ 18.6 18.2 19.9 INOSF 186 168 165 “Lesions overlap between two quadrants within the breast. Nos, not otherwise specitied. ‘Source: Winchester DJ, Chang HR, Graves TA, Menck HR, Bland KI, Winchester DP. A comparative analysis of lobular and ductal carcinoma of the breast: presentation, treatment, and outcomes. J Am Coll Surg 186: 416-422, 1998; with permission. Foster and Wood*2 have attempted to forecast the future of treatment of breast cancer. They believe that the current treatment of breast cancer will be changed by advances in molecular biology and other technological advances. We advise the interested student to read their excellent presentation. In a personal communication (2000) to the senior author of this chapter (JES), William C. Wood emphasized that successful treatment of breast cancer depends on understanding the anatomy of the breast: The local therapy of breast cancer has been anatomically based from the time of Halstead a century ago. As better understanding of the biology of the disease, both cellular and genetic, developed there came a sense that knowledge of the anatomy and embryology of the breast and its environs was less important, perhaps even anachronistic. The new techniques for diagnosis, prediction, and local therapy are rapidly reversing such ideas. A knowledge of lymphatic drainage, reflected in sentinel lymph node mapping and biopsy, makes it possible to perform surgical clearance of residual axillary metastases only for those patients whose disease warrants it. Understanding the non-segmental nature of breast ductal anatomy Is essential to properly evaluating and treating ductal carcinoma in situ (DCIS). The ability to identify genetic predisposition to breast cancer relieves half of the women with familial mutations already identified that they are free of the mutation. For those found to have BRCA 1 or BRCA 2 mutations, prophylactic ovarian surgery is a major consideration. Most do not require serious consideration of prophylactic mastectomy, butt for those who do, detailed anatomical knowledge required for prophylactic skin-sparing mastectomy with immediate reconstruction is essential for surgeons who would provide the best care. It is as true today as it was in the days of John Hunter that the best anatomist makes the best surgeon. The dictionary defines sentinel as "one who or that which watches or stands as if watching." Therefore, in anatomy or surgery, perhaps the sentinel node is the first site of metastatic disease,the watchdog in cancer. We agree with Borgstein and Meijer*3 that "the role of regional lymph node dissection in the treatment of most solid tumors remains enigmatic and controversial." To be more anatomically correct, the sentinel node is the first node receiving lymph from the primary tumor. The topographic and anatomic location of this node is not certain, but injection of blue dye or radio-labelled technicium will locate the node in the ipsilateral axilla by careful dissection. As Singletary“ stated, "Because of the significant frequency of false-negative results in [sentinel lymph node biopsy], which will depend upon the surgeon's experience, caution Is urged in determining when [axillary lymph node biopsy] can be safely eliminated in patients with a negative [sentinel lymph node biopsy). In 1977, Cabanas*® postulated the existence of a specific lymph node center relatively proximate tc a primary tumor and differentially identfable by lymphangiography, the first site of possible metastasis. The significance of his work on penile carcinoma was not fully appreciated at that time. In 1992, Morton et al.4€ independently hypothesized the existence of the sentinel node. We quote from their report on early stage melanoma Anew procedure was developed using vital dyes that permits intraoperative identification of the sentinel lymph node, the lymph node nearest the site of the primary melanoma, on the direct drainage pathway. The most likely site of early metastases, the sentinel node can be removed for immediate intraoperative study to Identify clinically occult melanoma cells. We successfully identified the sentinel node(s) in 194 of 237 lymphatic basins and detected metastases In 40 specimens (21%). . . Metastases were present in 47 (18%) of 259 sentinel nodes, while nonsentinel nodes were the sole site of metastases in only two of 3079 nodes from 194 lymphadenectomy specimens that had an Identifiable sentinel node, a false-negative rate of less than 1%. Thus, this technique identifies, with a high degree of accuracy, patients with early stage melanoma who have nodal metastases and are likely to benefit from radical lymphadenectomy. For the senior author (JES), questions surrounding the intersection of anatomy, biology and surgery make the sentinel node concept perhaps difficult to accept. Certainly, more work needs to be done ‘on the topographic anatomy of the sentinel node of the given anatomic entity with a solid tumor. The biology and overall philosophy of cancer is still an unsolved problem. Finally, the "radicality” of surgery and the type chosen for different cancers are points on which surgeons agree to disagree. The study of Albertini et al.47 indicated that lymphatic mapping Is possible in breast cancer patients and that the histologic status of the sentinel lymph node (or nodes) probably reflects the histologic status of the axillary nodes at risk. They concluded that if their results are confirmed by other Investigators, the combination of lymphatic mapping and selective lymphadenectomy might lead to more conservative treatment. O'Hea et al.4® advised that lymphatic mapping in breast surgery is technically feasible by injecting 0.3 mCi of technetium-39m unfiltered sulfur colloid in 4 ml of saline at 12, 3, 6, and 9 o'clock positions around the tumor in the breast tissues prior to surgery. This reliably identifies a sentinel node in most cases, and appears more accurate for T1 tumors than for larger lesions. Kern#? published an illustrated study in the hope that "the illustrations....will enable surgeons to perform subareolar injections of radiocolloid and blue dye in a safe and effective manner. Although dye-only SLN [sentinel lymph node] mapping can be successfully performed with high accuracy using the SA [subareolar] route, the addition of SA radiocolloid serves as an important aid to increase the efficiency of SLN biopsy, while keeping morbidity to a minimum." We quote from Smith et al.2°[S]ubareolar injection was as accurate, if not more accurate, than peritumoral injection for locating the [sentinel lymph node]. This technique is simpler than peritumoral injection and does not require injection under image guidance for nonpalpable lesions. Foster®! stated the following: “Initial data®2 indicate that if there is no evidence of metastasis to the sentinel node, the likelihood of detection of metastasis in other nodes in the regional basin Is very low (<2%). If this concept Is proved by confirmatory studies, complete axillary dissection may then be avoided in one half to two thirds of patients with invasive breast cancer." Snider et al.53 reported that in the staging of breast cancer, sentinel node biopsy with serial sectioning and immunohistochemical staining precisely predicts the status of the axillary lymph nodes and that most likely it will replace full axillary lymph node dissection. Linehan et al.54 advised blue-dye mapping and gamma-probe localization of sentinel lymph nodes using unfiltered Tc-99m sulfur colloid. \Velanovich and Szymanski°> found that of 827 patients with carcinoma of the breast who had had axillary lymph node dissection, 8.3 percent developed lymphedema, and that diminutions in quality of life accompanied lymphedema. They advised use of sentinel lymph node biopsy or selective axillary lymph node dissection to reduce the incidence of lymphedema. Nwariaku et al.5© reported that sentinel lymph node biopsy accurately predicts total axillary status and Is valuable in the surgical staging of carcinoma of the breast. Rubio et al.>7 also stated that the sentinel lymph node biopsy for carcinoma of breast staging is highly accurate. Bass et al.2% reportec that lymphatic mapping and sentinel lymph node biopsy are indispensable tools for treatment of breast cancer. Tanis et al.59 commented on lymphatic mapping. : Choosing the most attractive approach requires determining the aim of lymphatic mapping. A superficial injection technique may be adequate when the purpose is to spare patients without lymph node metastases in the axilla an unneccasry axillary node dissection. An intraparenchymal injection technique should be used when the additional purpose is to determine the stage as accurately as possible and to identify sentinel nodes elsewhere Feldman et al.6° reported that the accuracy of sentinel node biopsy in correctly predicting the status of remaining axillary lymph nodes may be limited in patients with large segmental breast excision before radiolocalization of the sentinel node. Their findings suggest that excisional biopsy should be avoided prior to lymphatic mapping for sentinel node biopsy (Fig. 3-23, Fig. 3-24). Fig 3-23.4 injection sites: Sentinel node Lymphatic dreinage pathway Large excision cavity Copyright 62006 by The MeGray-Hill Companias, Ine Al iches reserved Injections around the perimeter of the biopsy excision site with lymphatic drainage from the site are completely missing the sentinel node. Large excision biopsy results in Inaccurate lymphatic mapping (false negative). (Modified trom Feldman SM, Krag DN, McNally RK, Moor BB, Weaver DL, Klein P. Limitation in gamma probe localization of the sentinel node in breast cancer patients with large excisional biopsy. J Am Coll Surg 188:248-254, 1999; with, permission.)Injection sites Sentinel node lymphatic drainage pathway Large excision cavity Copyright ©2008 by The MeGran-HIll Companies, Ine All tights reserved, This ilustration shows injections around the perimeter of the biopsy site with lymphatic drainage to the sentinel node. Muttipte injections around large excision biopsy may improve accuracy of lymphatic mapping. (Modified trom Fekiman SM, Krag DN, McNally RK, Moor 88, Weaver DL, Klein P. Limitation in gamma probe localization of the sentinel node in breast cancer patients with large excisional biopsy. J Am Coll Surg 188:248-254, 1999; with permission.) Firead an Editorial Comment Giuliano®! stated, "There is no doubt that SLND [sentinel lymph node dissection] can accurately stage patients with breast cancer.” Winer et al.17 cautioned, "The initial results of lymphatic mapping and sentinel node biopsy are extremely promising. However, data on the long-term outcome of sentinel node biopsy alone in unselected populations and information on the ability of surgeons outside of centers of expertise doing a low volume of breast surgery are needed before it can be determined if sentinel node biopsy will replace axillary dissection as the standard of care for the node-negative or node-positive breast cancer." Luce! et al.©? wrote: SLND may indeed prove to be a major advance in the surgical treatment of breast cancer, but there remain a number of troubling issues, including routine use of IHC [immunohistochemistry] outside the clinical trial setting, and surgeon training in the procedure. We propose that surgeons with a high volume of breast cancer patients gain experience by performing confirmatory ALND [axillary lymph node dissection], and once eligible, enroll patients in the ongoing SLND clinical trials. These trials should answer many ofthe questions surrounding SLND, while protecting patient interests through the informed consent process, Tafra et al.63 proposed credentialing criteria for institutional acceptance of sentinel lymphadenectomy in lieu of axillary dissection, since badly performed sentinel node biopsy may be linked to unacceptably high false-negative rates, Bland®4 wrote that the status of the axillary lymphatics remains the single most important prognostic predictor for outcomes of carcinoma of the breast. Bland et al.©5 reported that the 10- year survival is worse in women with stage I or II breast cancer and who did not have axillary node dissection. Pack and Thomas® stated that positive axillary lymph nodes in early breast cancer are an indication for axillary node dissection Mustafa et al.©7 found that small breast cancer size does not affect survival and that nodal status remains the most powerful determinant in survival From an anatomic standpoint, we agree with the following statement by Bale et al.©8 : "In upper quadrants or deep breast cancers the interpectoral nodes may be the earliest sites of nodal metastasis, This may lead to false negative results in some sentinel node biopsies.” Winchester et al.©9 advised that if the sentinel node is free of metastatic disease, axillary node dissection "must be omitted" in patients with mammary carcinoma. By definition, a sentinel lymph node is the first lower node that receives lymph from the primary tumor. Hsueh et al.7° stated that sentinel node biopsy (SNB) is less invasive and as accurate as axillary lymph node dissection (ALND: in determining whether or not there is axillary node involvement. They cautioned, however, that because the accuracy of the procedure Is dependent upon the surgeon's capacity to Identify the sentinel node, patients should not be offered SNB without ALND until the surgeon Is confident in his skill with the technique. Kern?! demonstrated that "study of dye-only injections into the subareolar plexus demonstrates a high sentinel node identification rate, absent false-negative rate, and rapid learning curve." Morrow et al.72 stated that their study does not identify any advantage for the use of the more expensive and complex method of sentinel node identification using blue dye plus radioactivity compared with blue dye alone, even for surgeons learning the techniques. Morton and Ollila73 present the following thoughts about the "sentinel node hypothesis." Intraoperative lymphatic mapping and sentinel lymphadenectomy (LM/SL) is of potential diagnostic value for breast cancer and other solid tumors that metastasize to the regional lymph nodes, but unless we can demonstrate a survival benefit for early excision of tumor- Involved nodes, then LM/SL will not have direct therapeutic relevance. In other words, unless a tumor metastasizes to the regional nodes before distant sites, then a tumor-positive SN Is merely a marker for the metastatic phenotype. Hopefully, blood and tissue analyses using molecular and immunologic markers will confirm the sequential passage of tumor cells to regional lymph nodes and then to distant sites, thereby creating a therapeutic window of opportunity for lymphadenectomy while the tumor cells are confined to the SNs. However appealing the theory underlying LM/SL is, until the long-term results of the MSLT (Multicenter Selective Lymphadenectomy Trial) Indicate the efficacy of LM/SL as a therapeutic procedure, the theory remains a hypothesis with little scientific support from randomized trials. \Vetto et al.75 concluded that an accurate diagnosis of breast masses in males can be made by physical examination and fine needle aspiration. Vetto et al.76 reported that prognostic factors ofcarcinoma of the breast in males are similar to those of females. Contrary to anatomic evidence, there is a marked difference In mortality from lesions in different locations in the breast. In a series of 142 patients reported by Skandalakis et al.,77 the inner lower quadrant was the least frequently affected, but it had the highest relative mortality (Fig. 3-25). Fig. 3-25. 15 Incidence 328 cases Med. . ns 38.5 Mortality (% dying <5 yrs.) 142 patients allages Copygh: @2006 by The MeGrav-Hil Companies, tre i ches reserved ‘A. Localization of breast tumors in $28 patients. The upper lateral quadrant Is the most frequertly affected. B. Five- year mortality from breast tumors by location. Tumors of the inner lower quadrant are the most frequently fatal, (Moditied trom Skandalakis JE, Gray SW, Rowe JS Jr. Anatomical Complications in General Surgery. New York:McGraw-Hill, 1983; with permission) Cady78 posited breast cancer as largely a progressive disease, not a systemic one, and lists three basic principles of surgical oncology. The extent or radicalness of local resection, while directly related to local recurrence risk, does not affect survival «Lymph node metastases are also Indicators, but not governors, of outcome. «Lymph node metastatic cells, which have the capacity to lodge and grow in lymph nodes, may have no capacity to lodge or grow elsewhere. Ever the philosopher, Cady concluded: When I look back on the treatment of breast cancer patients during my career from training In the 1960s with the routine application of radical mastectomy, to patients seen in 2000, I can only imagine how foolish our current therapy will look to our successors In 2015. Morton7? gives this same theme a wry twist: A mammographic lesion that a skilled mammographer wished to re-evaluate in 3 months, an excisional biopsy specimen that was unimpressive grossly and initially interpreted officially as benign disease, a mastectomy specimen with 2 involved axillary lymph nodes, a patient living and well 15 years later after a course of chemotherapy - do these events represent a triumph of careful follow-up and appropriate therapy? Or do they represent the natural history of this disease in this particular patient? I still wonder. In agreement with Cady (quoted previously), Gervasoni et al.2° observed that "lymph node metastasis functions as an indicator of prognosis, not the controlling or determining factor of prognosis." The senior author of this chapter feels that more investigative work is necessary regarding the anatomic, biologic, and surgical approach to the lymphatics of cancer in general and to the sentinel lymph nodes in particular. Itis not our intention to become involved in the controversy surrounding the relative merits of the preceding procedures, or to discuss the virtues of radiation or chemotherapy, or the combinations of the various courses of treatment. The biology of breast cancer is not yet completely known. DeCosse8! wondered if the demise of radical mastectomy was premature. The water is muddy; we must wait for it to clear. orr et al.82 advised axillary lymph node dissection in all patients with carcinoma of the breast. Axillary dissection should be omitted only for women who have had an accurate sentinel node biopsy. Anatomy of the Triangular Bed of Mastectomy The triangular bed of radical mastectomy is formed by the cut pectoralis major and minor muscles medially (Fig. 3-19), the medial border of the latissimus dorsi muscle laterally, and the axillary vein superiorly. The serratus anterior and the subscapularis muscles form the floor of the triangle. The long thoracic nerve (Bell's) lies on the external surface of the serratus anterior muscle slightly anterior to the midaxillary line; the thoracodorsal and subscapular nerves lie on the subscapularis muscle.The triangular bed of a modified radical mastectomy, as described by Pickren and associates, 83 is similar, but the medial side is the upward and medially retracted axillary margin of the pectoralis major muscle (Fig. 3-26). This results in a smaller triangle, but one that is adequate for good dissection. Fig 3-26. Retractors Rotracted axillary margin (pectoralis ‘major & minar) Copyright ©2008 by The McGraw-Hill Companies, Ine. All tights reserved, The triangular bed of a modified radical mastectomy. The pectoralls muscles are retracted rather than removed. The {langle is only slightly smaller than that in Figure 3-19. (Moditied trom Skandalakis LJ, Vohman MD, Skandalakis JE, Gray SW. The axillary lymph nodes In radical and modified radical mastectomy. Am Surg 1979;45:552; with permission.) After the breast and the underlying fascia are removed, a good dissection consists of (1) removing remnants of the pectoralis major fascia at its axillary border; (2) entering the axilla by incising and stripping the axillary fascia; (3) further stripping the fascia of the pectoralis minor muscle (lower clavipectoral fascia); (4) exposing the axillary vein; (5) downward dissection of axillary fat and lymph nodes after ligating tributaries of the axillary vein from the thoracic wall; and (6) continuing the dissection downward, partially removing the fasciae of the serratus anterior muscle, the subscapularis muscle, and the medial border of the latissimus dorsi muscle. When the preceding steps are complete, the triangle is clean, The beautiful description of this procedure by Madden®4 is worth reading.Firead an Editorial Comment ANATOMIC COMPLICATIONS OF MASTECTOMY Skin Skin flaps must be kept thin, and all fat and glandular tissue must be removed to avoid recurrence of malignant disease. The choice of cautery or knife is up to the surgeon. Remember that the most frequent complication of mastectomy is skin necrosis. Abad incision of the axilla can, after cicatrization, leave a vertical scar that limits movement of the arm. An inadequate incision will invite local recurrence. The general rule is to remove healthy tissue three fingerbreadths (approximately 5 cm or 2 inches) from the edge of the tumor. Vascular Injury The sources of bleeding during mastectomy are: + the perforating arteries and veins, especially those of the first and second intercostal vessels + the axillary vein and its tributaries «the axillary artery and Its branches Firead an Editorial Comment The average blood loss during radical mastectomy has been estimated to be 732 ml.85 The perforating vessels should be ligated; the first three are too large for cautery. The axillary vein, if torn, must be ligated. The axillary artery is rarely injured; ®© but when repair is necessary, it must be done between bulldog clamps. Postoperative edema of the arm is a common sequel to radical mastectomy and extensive lymphadenectomy. According to Horsley,87 about 10% of radical mastectomy patients experience disabling lymphedema. At one time, obstruction to the axillary vein was considered an important factor in edema formation. Subsequent studies®8-89 have shown this is not so. Lymphatic obstruction or destruction appears to be the sole cause of edema, which appears transiently in abou half of the patients undergoing radical mastectomy. Organ Injury Pneumothorax is a possible danger during ligation of perforating vessels. The surgeon should use curved hemostats and not apply them at right angles. The pneumothorax is easily repaired, but the possible contamination of the pleural cavity with malignant cells is a delayed catastrophe. Zintel and Nay®6 had one pneumothorax among 249 consecutive radical mastectomies. Nerve Injury Thoracodorsal Nerve If the thoracodorsal nerve (middle subscapular) is cut, internal rotation and abduction are weakened, although there is no deformity.Long Thoracic Nerve Section of the nerve results in the "winged scapula" deformity Anterior Thoracic Nerves (Pectoral) Inadvertent division of the lateral pectoral nerve results in atrophy of the clavicular head, with resulting unsightly cosmetic deformity just inferior to the clavicle If branches of one or both pectoral nerves are Injured, the result will be atrophy of the pectoralis major and minor muscles. Brachial Plexus Direct injury to the brachial plexus is possible, but most injury is the result of stretching the nerves during operation. One patient in the series of 249 mastectomies of Zintel and Nay®® suffered transient injury to the plexus. Flap Complications Stevenson?° studied complications of flap surgery and individual flap complications. He stressed the Importance of a thorough anatomic knowledge of vascularization of the flap for successful surgery Inadequate Procedure To some surgeons, no procedure less than a full radical mastectomy Is considered adequate. This philosophy that adequacy of breast resection depends on removal of all metastatic nodes in addition to the breast itself Is, of course, questioned today by a great number of surgeons. We will not enter Into this discussion. Another measure of the adequacy of a mastectomy is the number of nodes actually removed from the axilla of the patient and examined by the pathologist Skandalakis et al.22 reexamined surgical specimens taken from 24 radical mastectomies and from 20 modified radical mastectomies. In the first group, 19.5 percent of the lymph nodes removed at operation escaped examination by the pathologist. In the second group, 7.7 percent were not found at first examination. In one patient, a node sectioned only at reexamination proved to be malignant. Most of the nodes overlooked in the beginning were very small and not palpable in the freshly excised tissue, These small nodes became barely visible after several weeks of formalin fixation. To recover more of these microscopic nodes, the pathologist should section at least five less-fatty areas of axillary tissue taken at random What is the modern view of axillary node dissection? Twenty years ago, Fisher and colleagues? stated that regional lymph nodes are primary indicators and not instigators of distal disease. They advised that lower axillary dissection is more than adequate to fulfill the alms of the operation. These authors believe that with removal of a few lymph nodes, the qualitative axillary nodal status (positive or negative) can be determined with accuracy. Firead an Editorial Comment REFERENCES 1, Berengario da Carpi J. A Short Introduction to Anatomy (Isagogae Breves), Lind LR (trans)