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configuration with decreased volume.Nipple-Areola Complex. The epidermis of the nipple-are-ola complex is pigmented and is variably corrugated. During puberty, the pigment becomes darker and the nipple assumes an elevated configuration. Throughout pregnancy, the areola Brunicardi_Ch17_p0541-p0612.indd 54401/03/19 5:04 PM 545THE BREASTCHAPTER 17Figure 17-3. Inactive human breast (100x). The epithelium, which is primarily ductal, is embedded in loose connective tissue. Dense connective tissue surrounds the terminal duct lobular units (TDLU). (Used with permission from Dr. Sindhu Menon, Consultant Histo-pathologist and Dr. Rahul Deb, Consultant Histopathologist and Lead Breast Pathologist, Royal Derby Hospital, Derby, UK.)Figure 17-4. Active human breast: pregnancy and lactation (160x). The alveolar epithelium becomes conspicuous during the early pro-liferative period. The alveolus is surrounded by cellular connective tissue. (Used with permission from Dr. Sindhu Menon, Consultant
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Surgery_Schwartz. configuration with decreased volume.Nipple-Areola Complex. The epidermis of the nipple-are-ola complex is pigmented and is variably corrugated. During puberty, the pigment becomes darker and the nipple assumes an elevated configuration. Throughout pregnancy, the areola Brunicardi_Ch17_p0541-p0612.indd 54401/03/19 5:04 PM 545THE BREASTCHAPTER 17Figure 17-3. Inactive human breast (100x). The epithelium, which is primarily ductal, is embedded in loose connective tissue. Dense connective tissue surrounds the terminal duct lobular units (TDLU). (Used with permission from Dr. Sindhu Menon, Consultant Histo-pathologist and Dr. Rahul Deb, Consultant Histopathologist and Lead Breast Pathologist, Royal Derby Hospital, Derby, UK.)Figure 17-4. Active human breast: pregnancy and lactation (160x). The alveolar epithelium becomes conspicuous during the early pro-liferative period. The alveolus is surrounded by cellular connective tissue. (Used with permission from Dr. Sindhu Menon, Consultant
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Surgery_Schwartz_3703
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The alveolar epithelium becomes conspicuous during the early pro-liferative period. The alveolus is surrounded by cellular connective tissue. (Used with permission from Dr. Sindhu Menon, Consultant Histopathologist and Dr. Rahul Deb, Consultant Histopathologist and Lead Breast Pathologist, Royal Derby Hospital, Derby, UK.)enlarges and pigmentation is further enhanced. The areola con-tains sebaceous glands, sweat glands, and accessory glands, which produce small elevations on the surface of the areola (Montgomery’s tubercles). Smooth muscle bundle fibers, which lie circumferentially in the dense connective tissue and longi-tudinally along the major ducts, extend upward into the nipple, where they are responsible for the nipple erection that occurs with various sensory stimuli. The dermal papilla at the tip of the nipple contains numerous sensory nerve endings and Meiss-ner’s corpuscles. This rich sensory innervation is of functional importance because the sucking of the infant
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Surgery_Schwartz. The alveolar epithelium becomes conspicuous during the early pro-liferative period. The alveolus is surrounded by cellular connective tissue. (Used with permission from Dr. Sindhu Menon, Consultant Histopathologist and Dr. Rahul Deb, Consultant Histopathologist and Lead Breast Pathologist, Royal Derby Hospital, Derby, UK.)enlarges and pigmentation is further enhanced. The areola con-tains sebaceous glands, sweat glands, and accessory glands, which produce small elevations on the surface of the areola (Montgomery’s tubercles). Smooth muscle bundle fibers, which lie circumferentially in the dense connective tissue and longi-tudinally along the major ducts, extend upward into the nipple, where they are responsible for the nipple erection that occurs with various sensory stimuli. The dermal papilla at the tip of the nipple contains numerous sensory nerve endings and Meiss-ner’s corpuscles. This rich sensory innervation is of functional importance because the sucking of the infant
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Surgery_Schwartz_3704
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dermal papilla at the tip of the nipple contains numerous sensory nerve endings and Meiss-ner’s corpuscles. This rich sensory innervation is of functional importance because the sucking of the infant initiates a chain of neurohumoral events that results in milk letdown.Inactive and Active Breast. Each lobe of the breast termi-nates in a major (lactiferous) duct (2–4 mm in diameter), which opens through a constricted orifice (0.4–0.7 mm in diameter) into the ampulla of the nipple (see Fig. 17-2). Immediately below the nipple-areola complex, each major duct has a dilated portion (lactiferous sinus), which is lined with stratified squa-mous epithelium. Major ducts are lined with two layers of cuboidal cells, whereas minor ducts are lined with a single layer of columnar or cuboidal cells. Myoepithelial cells of ectoder-mal origin reside between the epithelial cells in the basal lamina and contain myofibrils. In the inactive breast, the epithelium is sparse and consists primarily of ductal
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Surgery_Schwartz. dermal papilla at the tip of the nipple contains numerous sensory nerve endings and Meiss-ner’s corpuscles. This rich sensory innervation is of functional importance because the sucking of the infant initiates a chain of neurohumoral events that results in milk letdown.Inactive and Active Breast. Each lobe of the breast termi-nates in a major (lactiferous) duct (2–4 mm in diameter), which opens through a constricted orifice (0.4–0.7 mm in diameter) into the ampulla of the nipple (see Fig. 17-2). Immediately below the nipple-areola complex, each major duct has a dilated portion (lactiferous sinus), which is lined with stratified squa-mous epithelium. Major ducts are lined with two layers of cuboidal cells, whereas minor ducts are lined with a single layer of columnar or cuboidal cells. Myoepithelial cells of ectoder-mal origin reside between the epithelial cells in the basal lamina and contain myofibrils. In the inactive breast, the epithelium is sparse and consists primarily of ductal
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Surgery_Schwartz_3705
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cells of ectoder-mal origin reside between the epithelial cells in the basal lamina and contain myofibrils. In the inactive breast, the epithelium is sparse and consists primarily of ductal epithelium (Fig. 17-3). In the early phase of the menstrual cycle, minor ducts are cord-like with small lumina. With estrogen stimulation at the time of ovulation, alveolar epithelium increases in height, duct lumina become more prominent, and some secretions accumulate. When the hormonal stimulation decreases, the alveolar epithe-lium regresses.With pregnancy, the breast undergoes proliferative and developmental maturation. As the breast enlarges in response to hormonal stimulation, lymphocytes, plasma cells, and eosin-ophils accumulate within the connective tissues. The minor ducts branch and alveoli develop. Development of the alveoli is asymmetric, and variations in the degree of development may occur within a single lobule (Fig. 17-4). With parturition, enlargement of the breasts occurs via
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Surgery_Schwartz. cells of ectoder-mal origin reside between the epithelial cells in the basal lamina and contain myofibrils. In the inactive breast, the epithelium is sparse and consists primarily of ductal epithelium (Fig. 17-3). In the early phase of the menstrual cycle, minor ducts are cord-like with small lumina. With estrogen stimulation at the time of ovulation, alveolar epithelium increases in height, duct lumina become more prominent, and some secretions accumulate. When the hormonal stimulation decreases, the alveolar epithe-lium regresses.With pregnancy, the breast undergoes proliferative and developmental maturation. As the breast enlarges in response to hormonal stimulation, lymphocytes, plasma cells, and eosin-ophils accumulate within the connective tissues. The minor ducts branch and alveoli develop. Development of the alveoli is asymmetric, and variations in the degree of development may occur within a single lobule (Fig. 17-4). With parturition, enlargement of the breasts occurs via
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develop. Development of the alveoli is asymmetric, and variations in the degree of development may occur within a single lobule (Fig. 17-4). With parturition, enlargement of the breasts occurs via hypertrophy of alveolar epithelium and accumulation of secretory products in the lumina of the minor ducts. Alveolar epithelium contains abundant endo-plasmic reticulum, large mitochondria, Golgi complexes, and dense lysosomes. Two distinct substances are produced by the alveolar epithelium: (a) the protein component of milk, which is synthesized in the endoplasmic reticulum (merocrine secretion); and (b) the lipid component of milk (apocrine secretion), which forms as free lipid droplets in the cytoplasm. Milk released in the first few days after parturition is called colostrum and has low lipid content but contains considerable quantities of anti-bodies. The lymphocytes and plasma cells that accumulate within the connective tissues of the breast are the source of the antibody component.
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Surgery_Schwartz. develop. Development of the alveoli is asymmetric, and variations in the degree of development may occur within a single lobule (Fig. 17-4). With parturition, enlargement of the breasts occurs via hypertrophy of alveolar epithelium and accumulation of secretory products in the lumina of the minor ducts. Alveolar epithelium contains abundant endo-plasmic reticulum, large mitochondria, Golgi complexes, and dense lysosomes. Two distinct substances are produced by the alveolar epithelium: (a) the protein component of milk, which is synthesized in the endoplasmic reticulum (merocrine secretion); and (b) the lipid component of milk (apocrine secretion), which forms as free lipid droplets in the cytoplasm. Milk released in the first few days after parturition is called colostrum and has low lipid content but contains considerable quantities of anti-bodies. The lymphocytes and plasma cells that accumulate within the connective tissues of the breast are the source of the antibody component.
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content but contains considerable quantities of anti-bodies. The lymphocytes and plasma cells that accumulate within the connective tissues of the breast are the source of the antibody component. With subsequent reduction in the number of these cells, the production of colostrum decreases and lipid-rich milk is released.Blood Supply, Innervation, and Lymphatics. The breast receives its principal blood supply from: (a) perforating branches of the internal mammary artery; (b) lateral branches of the poste-rior intercostal arteries; and (c) branches from the axillary artery, including the highest thoracic, lateral thoracic, and pectoral branches of the thoracoacromial artery (Fig. 17-5). The second, third, and fourth anterior intercostal perforators and branches of the internal mammary artery arborize in the breast as the medial mammary arteries. The lateral thoracic artery gives off branches to the serratus anterior, pectoralis major and pectoralis minor, and subscapularis muscles. It
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Surgery_Schwartz. content but contains considerable quantities of anti-bodies. The lymphocytes and plasma cells that accumulate within the connective tissues of the breast are the source of the antibody component. With subsequent reduction in the number of these cells, the production of colostrum decreases and lipid-rich milk is released.Blood Supply, Innervation, and Lymphatics. The breast receives its principal blood supply from: (a) perforating branches of the internal mammary artery; (b) lateral branches of the poste-rior intercostal arteries; and (c) branches from the axillary artery, including the highest thoracic, lateral thoracic, and pectoral branches of the thoracoacromial artery (Fig. 17-5). The second, third, and fourth anterior intercostal perforators and branches of the internal mammary artery arborize in the breast as the medial mammary arteries. The lateral thoracic artery gives off branches to the serratus anterior, pectoralis major and pectoralis minor, and subscapularis muscles. It
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arborize in the breast as the medial mammary arteries. The lateral thoracic artery gives off branches to the serratus anterior, pectoralis major and pectoralis minor, and subscapularis muscles. It also gives rise to lateral mammary branches. The veins of the breast and chest wall follow the course of the arteries, with venous drainage being toward the axilla. The three principal groups of veins are: (a) per-forating branches of the internal thoracic vein, (b) perforating branches of the posterior intercostal veins, and (c) tributaries of the axillary vein. Batson’s vertebral venous plexus, which invests the vertebrae and extends from the base of the skull to the sacrum, may provide a route for breast cancer metastases to the vertebrae, skull, pelvic bones, and central nervous system. Lymph vessels generally parallel the course of blood vessels.1Brunicardi_Ch17_p0541-p0612.indd 54501/03/19 5:04 PM 546SPECIFIC CONSIDERATIONSPART IIFigure 17-5. Arterial supply to the breast, axilla,
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Surgery_Schwartz. arborize in the breast as the medial mammary arteries. The lateral thoracic artery gives off branches to the serratus anterior, pectoralis major and pectoralis minor, and subscapularis muscles. It also gives rise to lateral mammary branches. The veins of the breast and chest wall follow the course of the arteries, with venous drainage being toward the axilla. The three principal groups of veins are: (a) per-forating branches of the internal thoracic vein, (b) perforating branches of the posterior intercostal veins, and (c) tributaries of the axillary vein. Batson’s vertebral venous plexus, which invests the vertebrae and extends from the base of the skull to the sacrum, may provide a route for breast cancer metastases to the vertebrae, skull, pelvic bones, and central nervous system. Lymph vessels generally parallel the course of blood vessels.1Brunicardi_Ch17_p0541-p0612.indd 54501/03/19 5:04 PM 546SPECIFIC CONSIDERATIONSPART IIFigure 17-5. Arterial supply to the breast, axilla,
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vessels generally parallel the course of blood vessels.1Brunicardi_Ch17_p0541-p0612.indd 54501/03/19 5:04 PM 546SPECIFIC CONSIDERATIONSPART IIFigure 17-5. Arterial supply to the breast, axilla, and chest wall. (Reproduced with permission from Bland KI, Copeland EMI: The Breast: Comprehensive Management of Benign and Malignant Diseases, 4th ed. Philadelphia, PA: Elsevier/Saunders; 2009.)Figure 17-6. Lymphatic pathways of the breast. Arrows indicate the direction of lymph flow. (Visual Art: © 2013. The University of Texas MD Anderson Cancer Center.)Figure 17-7. Axillary lymph node groups. Level I includes lymph nodes located lateral to the pectoralis minor muscle; level II includes lymph nodes located deep to the pectoralis minor; and level III includes lymph nodes located medial to the pectoralis minor. The axillary vein with its major tributaries and the supracla-vicular lymph node group are also illustrated. (Visual Art: © 2013.The University of Texas MD Anderson Cancer
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Surgery_Schwartz. vessels generally parallel the course of blood vessels.1Brunicardi_Ch17_p0541-p0612.indd 54501/03/19 5:04 PM 546SPECIFIC CONSIDERATIONSPART IIFigure 17-5. Arterial supply to the breast, axilla, and chest wall. (Reproduced with permission from Bland KI, Copeland EMI: The Breast: Comprehensive Management of Benign and Malignant Diseases, 4th ed. Philadelphia, PA: Elsevier/Saunders; 2009.)Figure 17-6. Lymphatic pathways of the breast. Arrows indicate the direction of lymph flow. (Visual Art: © 2013. The University of Texas MD Anderson Cancer Center.)Figure 17-7. Axillary lymph node groups. Level I includes lymph nodes located lateral to the pectoralis minor muscle; level II includes lymph nodes located deep to the pectoralis minor; and level III includes lymph nodes located medial to the pectoralis minor. The axillary vein with its major tributaries and the supracla-vicular lymph node group are also illustrated. (Visual Art: © 2013.The University of Texas MD Anderson Cancer
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to the pectoralis minor. The axillary vein with its major tributaries and the supracla-vicular lymph node group are also illustrated. (Visual Art: © 2013.The University of Texas MD Anderson Cancer Center.)Lateral cutaneous branches of the third through sixth inter-costal nerves provide sensory innervation of the breast (lateral mammary branches) and of the anterolateral chest wall. These branches exit the intercostal spaces between slips of the serratus anterior muscle. Cutaneous branches that arise from the cervical plexus, specifically the anterior branches of the supraclavicular nerve, supply a limited area of skin over the upper portion of the breast. The intercostobrachial nerve is the lateral cutane-ous branch of the second intercostal nerve and may be visual-ized during surgical dissection of the axilla. Resection of the intercostobrachial nerve causes loss of sensation over the medial aspect of the upper arm.The boundaries for lymph drainage of the axilla are not well
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Surgery_Schwartz. to the pectoralis minor. The axillary vein with its major tributaries and the supracla-vicular lymph node group are also illustrated. (Visual Art: © 2013.The University of Texas MD Anderson Cancer Center.)Lateral cutaneous branches of the third through sixth inter-costal nerves provide sensory innervation of the breast (lateral mammary branches) and of the anterolateral chest wall. These branches exit the intercostal spaces between slips of the serratus anterior muscle. Cutaneous branches that arise from the cervical plexus, specifically the anterior branches of the supraclavicular nerve, supply a limited area of skin over the upper portion of the breast. The intercostobrachial nerve is the lateral cutane-ous branch of the second intercostal nerve and may be visual-ized during surgical dissection of the axilla. Resection of the intercostobrachial nerve causes loss of sensation over the medial aspect of the upper arm.The boundaries for lymph drainage of the axilla are not well
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dissection of the axilla. Resection of the intercostobrachial nerve causes loss of sensation over the medial aspect of the upper arm.The boundaries for lymph drainage of the axilla are not well demarcated, and there is considerable variation in the posi-tion of the axillary lymph nodes. The six axillary lymph node groups recognized by surgeons (Figs. 17-6 and 17-7) are: (a) the axillary vein group (lateral), which consists of four to six lymph nodes that lie medial or posterior to the vein and receive most of the lymph drainage from the upper extremity; (b) the external mammary group (anterior or pectoral group), which consists of five to six lymph nodes that lie along the lower border of the pectoralis minor muscle contiguous with the lateral thoracic vessels and receive most of the lymph drainage from the lat-eral aspect of the breast; (c) the scapular group (posterior or subscapular), which consists of five to seven lymph nodes that lie along the posterior wall of the axilla at the
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Surgery_Schwartz. dissection of the axilla. Resection of the intercostobrachial nerve causes loss of sensation over the medial aspect of the upper arm.The boundaries for lymph drainage of the axilla are not well demarcated, and there is considerable variation in the posi-tion of the axillary lymph nodes. The six axillary lymph node groups recognized by surgeons (Figs. 17-6 and 17-7) are: (a) the axillary vein group (lateral), which consists of four to six lymph nodes that lie medial or posterior to the vein and receive most of the lymph drainage from the upper extremity; (b) the external mammary group (anterior or pectoral group), which consists of five to six lymph nodes that lie along the lower border of the pectoralis minor muscle contiguous with the lateral thoracic vessels and receive most of the lymph drainage from the lat-eral aspect of the breast; (c) the scapular group (posterior or subscapular), which consists of five to seven lymph nodes that lie along the posterior wall of the axilla at the
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drainage from the lat-eral aspect of the breast; (c) the scapular group (posterior or subscapular), which consists of five to seven lymph nodes that lie along the posterior wall of the axilla at the lateral border of the scapula contiguous with the subscapular vessels and receive lymph drainage principally from the lower posterior neck, the posterior trunk, and the posterior shoulder; (d) the central group, which consists of three or four sets of lymph nodes that are embedded in the fat of the axilla lying immediately posterior to the pectoralis minor muscle and receive lymph drainage both from the axillary vein, external mammary, and scapular groups of lymph nodes, and directly from the breast; (e) the subcla-vicular group (apical), which consists of six to twelve sets of lymph nodes that lie posterior and superior to the upper bor-der of the pectoralis minor muscle and receive lymph drainage from all of the other groups of axillary lymph nodes; and (f) the interpectoral group
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Surgery_Schwartz. drainage from the lat-eral aspect of the breast; (c) the scapular group (posterior or subscapular), which consists of five to seven lymph nodes that lie along the posterior wall of the axilla at the lateral border of the scapula contiguous with the subscapular vessels and receive lymph drainage principally from the lower posterior neck, the posterior trunk, and the posterior shoulder; (d) the central group, which consists of three or four sets of lymph nodes that are embedded in the fat of the axilla lying immediately posterior to the pectoralis minor muscle and receive lymph drainage both from the axillary vein, external mammary, and scapular groups of lymph nodes, and directly from the breast; (e) the subcla-vicular group (apical), which consists of six to twelve sets of lymph nodes that lie posterior and superior to the upper bor-der of the pectoralis minor muscle and receive lymph drainage from all of the other groups of axillary lymph nodes; and (f) the interpectoral group
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that lie posterior and superior to the upper bor-der of the pectoralis minor muscle and receive lymph drainage from all of the other groups of axillary lymph nodes; and (f) the interpectoral group (Rotter’s lymph nodes), which consists of one to four lymph nodes that are interposed between the pec-toralis major and pectoralis minor muscles and receive lymph drainage directly from the breast. The lymph fluid that passes Brunicardi_Ch17_p0541-p0612.indd 54601/03/19 5:04 PM 547THE BREASTCHAPTER 17through the interpectoral group of lymph nodes passes directly into the central and subclavicular groups.As indicated in Fig. 17-7, the lymph node groups are assigned levels according to their anatomic relationship to the pectoralis minor muscle. Lymph nodes located lateral to or below the lower border of the pectoralis minor muscle are referred to as level I lymph nodes, which include the axillary vein, external mammary, and scapular groups. Lymph nodes located superficial or deep to the
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Surgery_Schwartz. that lie posterior and superior to the upper bor-der of the pectoralis minor muscle and receive lymph drainage from all of the other groups of axillary lymph nodes; and (f) the interpectoral group (Rotter’s lymph nodes), which consists of one to four lymph nodes that are interposed between the pec-toralis major and pectoralis minor muscles and receive lymph drainage directly from the breast. The lymph fluid that passes Brunicardi_Ch17_p0541-p0612.indd 54601/03/19 5:04 PM 547THE BREASTCHAPTER 17through the interpectoral group of lymph nodes passes directly into the central and subclavicular groups.As indicated in Fig. 17-7, the lymph node groups are assigned levels according to their anatomic relationship to the pectoralis minor muscle. Lymph nodes located lateral to or below the lower border of the pectoralis minor muscle are referred to as level I lymph nodes, which include the axillary vein, external mammary, and scapular groups. Lymph nodes located superficial or deep to the
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Surgery_Schwartz_3714
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border of the pectoralis minor muscle are referred to as level I lymph nodes, which include the axillary vein, external mammary, and scapular groups. Lymph nodes located superficial or deep to the pectoralis minor muscle are referred to as level II lymph nodes, which include the central and interpectoral groups. Lymph nodes located medial to or above the upper border of the pectoralis minor muscle are referred to as level III lymph nodes, which consist of the subclavicular group. The plexus of lymph vessels in the breast arises in the interlobular connective tissue and in the walls of the lactiferous ducts and communicates with the subareolar plexus of lymph vessels. Efferent lymph vessels from the breast pass around the lateral edge of the pectoralis major muscle and pierce the clavipectoral fascia, ending in the external mammary (anterior, pectoral) group of lymph nodes. Some lymph vessels may travel directly to the subscapular (pos-terior, scapular) group of lymph nodes. From the
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Surgery_Schwartz. border of the pectoralis minor muscle are referred to as level I lymph nodes, which include the axillary vein, external mammary, and scapular groups. Lymph nodes located superficial or deep to the pectoralis minor muscle are referred to as level II lymph nodes, which include the central and interpectoral groups. Lymph nodes located medial to or above the upper border of the pectoralis minor muscle are referred to as level III lymph nodes, which consist of the subclavicular group. The plexus of lymph vessels in the breast arises in the interlobular connective tissue and in the walls of the lactiferous ducts and communicates with the subareolar plexus of lymph vessels. Efferent lymph vessels from the breast pass around the lateral edge of the pectoralis major muscle and pierce the clavipectoral fascia, ending in the external mammary (anterior, pectoral) group of lymph nodes. Some lymph vessels may travel directly to the subscapular (pos-terior, scapular) group of lymph nodes. From the
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fascia, ending in the external mammary (anterior, pectoral) group of lymph nodes. Some lymph vessels may travel directly to the subscapular (pos-terior, scapular) group of lymph nodes. From the upper part of the breast, a few lymph vessels pass directly to the subclavicular (api-cal) group of lymph nodes. The axillary lymph nodes usually receive >75% of the lymph drainage from the breast. The rest is derived primarily from the medial aspect of the breast, flows through the lymph vessels that accompany the per-forating branches of the internal mammary artery, and enters the parasternal (internal mammary) group of lymph nodes.PHYSIOLOGY OF THE BREASTBreast Development and FunctionBreast development and function are initiated by a variety of hormonal stimuli, including estrogen, progesterone, prolactin, oxytocin, thyroid hormone, cortisol, and growth hormone.17,18 Estrogen, progesterone, and prolactin especially have profound trophic effects that are essential to normal breast
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Surgery_Schwartz. fascia, ending in the external mammary (anterior, pectoral) group of lymph nodes. Some lymph vessels may travel directly to the subscapular (pos-terior, scapular) group of lymph nodes. From the upper part of the breast, a few lymph vessels pass directly to the subclavicular (api-cal) group of lymph nodes. The axillary lymph nodes usually receive >75% of the lymph drainage from the breast. The rest is derived primarily from the medial aspect of the breast, flows through the lymph vessels that accompany the per-forating branches of the internal mammary artery, and enters the parasternal (internal mammary) group of lymph nodes.PHYSIOLOGY OF THE BREASTBreast Development and FunctionBreast development and function are initiated by a variety of hormonal stimuli, including estrogen, progesterone, prolactin, oxytocin, thyroid hormone, cortisol, and growth hormone.17,18 Estrogen, progesterone, and prolactin especially have profound trophic effects that are essential to normal breast
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prolactin, oxytocin, thyroid hormone, cortisol, and growth hormone.17,18 Estrogen, progesterone, and prolactin especially have profound trophic effects that are essential to normal breast develop-ment and function. Estrogen initiates ductal development, whereas progesterone is responsible for differentiation of epithe-lium and for lobular development. Prolactin is the primary hor-monal stimulus for lactogenesis in late pregnancy and the postpartum period. It upregulates hormone receptors and stimu-lates epithelial development. Fig. 17-8 depicts the secretion of neurotrophic hormones from the hypothalamus, which is respon-sible for regulation of the secretion of the hormones that affect the breast tissues. The gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) regulate the release of estrogen and progesterone from the ovaries. In turn, the release of LH and FSH from the basophilic cells of the anterior pituitary is regulated by the secretion of
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Surgery_Schwartz. prolactin, oxytocin, thyroid hormone, cortisol, and growth hormone.17,18 Estrogen, progesterone, and prolactin especially have profound trophic effects that are essential to normal breast develop-ment and function. Estrogen initiates ductal development, whereas progesterone is responsible for differentiation of epithe-lium and for lobular development. Prolactin is the primary hor-monal stimulus for lactogenesis in late pregnancy and the postpartum period. It upregulates hormone receptors and stimu-lates epithelial development. Fig. 17-8 depicts the secretion of neurotrophic hormones from the hypothalamus, which is respon-sible for regulation of the secretion of the hormones that affect the breast tissues. The gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) regulate the release of estrogen and progesterone from the ovaries. In turn, the release of LH and FSH from the basophilic cells of the anterior pituitary is regulated by the secretion of
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(FSH) regulate the release of estrogen and progesterone from the ovaries. In turn, the release of LH and FSH from the basophilic cells of the anterior pituitary is regulated by the secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus. Positive and negative feedback effects of circulating estrogen and progesterone regulate the secretion of LH, FSH, and GnRH. These hormones are respon-sible for the development, function, and maintenance of breast tissues (Fig. 17-9A). In the female neonate, circulating estrogen and progesterone levels decrease after birth and remain low throughout childhood because of the sensitivity of 23GRFLH-RHDopamineOxy/ADHTRHCRF-Figure 17-8. Overview of the neuroendocrine con-trol of breast development and function. ADH = antidiuretic hormone; CRF = corticotropin-releasing factor; GRF = growth hormone releasing factor; LH-RH = luteinizing hormone–releasing hormone; Oxy = oxytocin; TRH = thyrotropin-releasing hor-mone. (Reproduced with
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Surgery_Schwartz. (FSH) regulate the release of estrogen and progesterone from the ovaries. In turn, the release of LH and FSH from the basophilic cells of the anterior pituitary is regulated by the secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus. Positive and negative feedback effects of circulating estrogen and progesterone regulate the secretion of LH, FSH, and GnRH. These hormones are respon-sible for the development, function, and maintenance of breast tissues (Fig. 17-9A). In the female neonate, circulating estrogen and progesterone levels decrease after birth and remain low throughout childhood because of the sensitivity of 23GRFLH-RHDopamineOxy/ADHTRHCRF-Figure 17-8. Overview of the neuroendocrine con-trol of breast development and function. ADH = antidiuretic hormone; CRF = corticotropin-releasing factor; GRF = growth hormone releasing factor; LH-RH = luteinizing hormone–releasing hormone; Oxy = oxytocin; TRH = thyrotropin-releasing hor-mone. (Reproduced with
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CRF = corticotropin-releasing factor; GRF = growth hormone releasing factor; LH-RH = luteinizing hormone–releasing hormone; Oxy = oxytocin; TRH = thyrotropin-releasing hor-mone. (Reproduced with permission from Bland KI, Copeland EMI: The Breast: Comprehensive Man-agement of Benign and Malignant Diseases, 4th ed. Philadelphia, PA: Elsevier/Saunders; 2009.)Brunicardi_Ch17_p0541-p0612.indd 54701/03/19 5:04 PM 548SPECIFIC CONSIDERATIONSPART IIABCDFigure 17-9. The breast at different physi-ologic stages. The central column contains three-dimensional depictions of microscopic structures. A. Adolescence. B. Pregnancy. C. Lactation. D. Senescence.the hypothalamic-pituitary axis to negative feedback from these hormones. With the onset of puberty, there is a decrease in the sensitivity of the hypothalamic-pituitary axis to negative feed-back and an increase in its sensitivity to positive feedback from estrogen. These physiologic events initiate an increase in GnRH, FSH, and LH secretion
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Surgery_Schwartz. CRF = corticotropin-releasing factor; GRF = growth hormone releasing factor; LH-RH = luteinizing hormone–releasing hormone; Oxy = oxytocin; TRH = thyrotropin-releasing hor-mone. (Reproduced with permission from Bland KI, Copeland EMI: The Breast: Comprehensive Man-agement of Benign and Malignant Diseases, 4th ed. Philadelphia, PA: Elsevier/Saunders; 2009.)Brunicardi_Ch17_p0541-p0612.indd 54701/03/19 5:04 PM 548SPECIFIC CONSIDERATIONSPART IIABCDFigure 17-9. The breast at different physi-ologic stages. The central column contains three-dimensional depictions of microscopic structures. A. Adolescence. B. Pregnancy. C. Lactation. D. Senescence.the hypothalamic-pituitary axis to negative feedback from these hormones. With the onset of puberty, there is a decrease in the sensitivity of the hypothalamic-pituitary axis to negative feed-back and an increase in its sensitivity to positive feedback from estrogen. These physiologic events initiate an increase in GnRH, FSH, and LH secretion
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Surgery_Schwartz_3719
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Surgery_Schwartz
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hypothalamic-pituitary axis to negative feed-back and an increase in its sensitivity to positive feedback from estrogen. These physiologic events initiate an increase in GnRH, FSH, and LH secretion and ultimately an increase in estrogen and progesterone secretion by the ovaries, leading to establish-ment of the menstrual cycle. At the beginning of the menstrual cycle, there is an increase in the size and density of the breasts, which is followed by engorgement of the breast tissues and epi-thelial proliferation. With the onset of menstruation, the breast engorgement subsides and epithelial proliferation decreases.Pregnancy, Lactation, and SenescenceA dramatic increase in circulating ovarian and placental estro-gens and progestins is evident during pregnancy, which initiates striking alterations in the form and substance of the breast (see Fig. 17-9B).17-19 The breast enlarges as the ductal and lobular epithelium proliferates, the areolar skin darkens, and the acces-sory areolar glands
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Surgery_Schwartz. hypothalamic-pituitary axis to negative feed-back and an increase in its sensitivity to positive feedback from estrogen. These physiologic events initiate an increase in GnRH, FSH, and LH secretion and ultimately an increase in estrogen and progesterone secretion by the ovaries, leading to establish-ment of the menstrual cycle. At the beginning of the menstrual cycle, there is an increase in the size and density of the breasts, which is followed by engorgement of the breast tissues and epi-thelial proliferation. With the onset of menstruation, the breast engorgement subsides and epithelial proliferation decreases.Pregnancy, Lactation, and SenescenceA dramatic increase in circulating ovarian and placental estro-gens and progestins is evident during pregnancy, which initiates striking alterations in the form and substance of the breast (see Fig. 17-9B).17-19 The breast enlarges as the ductal and lobular epithelium proliferates, the areolar skin darkens, and the acces-sory areolar glands
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Surgery_Schwartz_3720
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Surgery_Schwartz
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in the form and substance of the breast (see Fig. 17-9B).17-19 The breast enlarges as the ductal and lobular epithelium proliferates, the areolar skin darkens, and the acces-sory areolar glands (Montgomery’s glands) become prominent. In the first and second trimesters, the minor ducts branch and develop. During the third trimester, fat droplets accumulate in the alveolar epithelium, and colostrum fills the alveolar and duc-tal spaces. In late pregnancy, prolactin stimulates the synthesis of milk fats and proteins.After delivery of the placenta, circulating progesterone and estrogen levels decrease, permitting full expression of the lactogenic action of prolactin. Milk production and release are controlled by neural reflex arcs that originate in nerve endings of the nipple-areola complex. Maintenance of lactation requires regular stimulation of these neural reflexes, which results in prolactin secretion and milk letdown. Oxytocin release results from the auditory, visual, and olfactory
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Surgery_Schwartz. in the form and substance of the breast (see Fig. 17-9B).17-19 The breast enlarges as the ductal and lobular epithelium proliferates, the areolar skin darkens, and the acces-sory areolar glands (Montgomery’s glands) become prominent. In the first and second trimesters, the minor ducts branch and develop. During the third trimester, fat droplets accumulate in the alveolar epithelium, and colostrum fills the alveolar and duc-tal spaces. In late pregnancy, prolactin stimulates the synthesis of milk fats and proteins.After delivery of the placenta, circulating progesterone and estrogen levels decrease, permitting full expression of the lactogenic action of prolactin. Milk production and release are controlled by neural reflex arcs that originate in nerve endings of the nipple-areola complex. Maintenance of lactation requires regular stimulation of these neural reflexes, which results in prolactin secretion and milk letdown. Oxytocin release results from the auditory, visual, and olfactory
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Surgery_Schwartz_3721
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of lactation requires regular stimulation of these neural reflexes, which results in prolactin secretion and milk letdown. Oxytocin release results from the auditory, visual, and olfactory stimuli associated with nursing. Oxytocin initiates contraction of the myoepithelial cells, which results in compression of alveoli and expulsion of milk into the lactiferous sinuses. After weaning of the infant, prolactin and oxytocin release decreases. Dormant milk causes increased pressure within the ducts and alveoli, which results in atrophy of the epithelium (Fig. 17-9C). With menopause, there is a decrease in the secretion of estrogen and progesterone by Brunicardi_Ch17_p0541-p0612.indd 54801/03/19 5:04 PM 549THE BREASTCHAPTER 17Table 17-1Pathophysiologic mechanisms of gynecomastia I. Estrogen excess states A. Gonadal origin 1. True hermaphroditism 2. Gonadal stromal (nongerminal) neoplasms of the testis a. Leydig cell (interstitial) b. Sertoli cell c. Granulosa-theca cell 3. Germ cell
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Surgery_Schwartz. of lactation requires regular stimulation of these neural reflexes, which results in prolactin secretion and milk letdown. Oxytocin release results from the auditory, visual, and olfactory stimuli associated with nursing. Oxytocin initiates contraction of the myoepithelial cells, which results in compression of alveoli and expulsion of milk into the lactiferous sinuses. After weaning of the infant, prolactin and oxytocin release decreases. Dormant milk causes increased pressure within the ducts and alveoli, which results in atrophy of the epithelium (Fig. 17-9C). With menopause, there is a decrease in the secretion of estrogen and progesterone by Brunicardi_Ch17_p0541-p0612.indd 54801/03/19 5:04 PM 549THE BREASTCHAPTER 17Table 17-1Pathophysiologic mechanisms of gynecomastia I. Estrogen excess states A. Gonadal origin 1. True hermaphroditism 2. Gonadal stromal (nongerminal) neoplasms of the testis a. Leydig cell (interstitial) b. Sertoli cell c. Granulosa-theca cell 3. Germ cell
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Surgery_Schwartz_3722
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Surgery_Schwartz
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excess states A. Gonadal origin 1. True hermaphroditism 2. Gonadal stromal (nongerminal) neoplasms of the testis a. Leydig cell (interstitial) b. Sertoli cell c. Granulosa-theca cell 3. Germ cell tumors a. Choriocarcinoma b. Seminoma, teratoma c. Embryonal carcinoma B. Nontesticular tumors 1. Adrenal cortical neoplasms 2. Lung carcinoma 3. Hepatocellular carcinoma C. Endocrine disorders D. Diseases of the liver—nonalcoholic and alcoholic cirrhosis E. Nutrition alteration states II. Androgen deficiency states A. Senescence B. Hypoandrogenic states (hypogonadism) 1. Primary testicular failure a. Klinefelter’s syndrome (XXY) b. Reifenstein’s syndrome c. Rosewater-Gwinup-Hamwi familial gynecomastia d. Kallmann syndrome e. Kennedy’s disease with associated gynecomastia f. Eunuchoidal state (congenital anorchia) g. Hereditary defects of androgen biosynthesis h. Adrenocorticotropic hormone deficiency 2. Secondary testicular
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Surgery_Schwartz. excess states A. Gonadal origin 1. True hermaphroditism 2. Gonadal stromal (nongerminal) neoplasms of the testis a. Leydig cell (interstitial) b. Sertoli cell c. Granulosa-theca cell 3. Germ cell tumors a. Choriocarcinoma b. Seminoma, teratoma c. Embryonal carcinoma B. Nontesticular tumors 1. Adrenal cortical neoplasms 2. Lung carcinoma 3. Hepatocellular carcinoma C. Endocrine disorders D. Diseases of the liver—nonalcoholic and alcoholic cirrhosis E. Nutrition alteration states II. Androgen deficiency states A. Senescence B. Hypoandrogenic states (hypogonadism) 1. Primary testicular failure a. Klinefelter’s syndrome (XXY) b. Reifenstein’s syndrome c. Rosewater-Gwinup-Hamwi familial gynecomastia d. Kallmann syndrome e. Kennedy’s disease with associated gynecomastia f. Eunuchoidal state (congenital anorchia) g. Hereditary defects of androgen biosynthesis h. Adrenocorticotropic hormone deficiency 2. Secondary testicular
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Surgery_Schwartz_3723
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Surgery_Schwartz
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disease with associated gynecomastia f. Eunuchoidal state (congenital anorchia) g. Hereditary defects of androgen biosynthesis h. Adrenocorticotropic hormone deficiency 2. Secondary testicular failure a. Trauma b. Orchitis c. Cryptorchidism d. Irradiation C. Renal failure III. Pharmacologic causes IV. Systemic diseases with idiopathic mechanismsthe ovaries and involution of the ducts and alveoli of the breast. The surrounding fibrous connective tissue increases in density, and breast tissues are replaced by adipose tissues (Fig. 17-9D).GynecomastiaGynecomastia refers to an enlarged breast in the male.20 Physi-ologic gynecomastia usually occurs during three phases of life: the neonatal period, adolescence, and senescence. Common to each of these phases is an excess of circulating estrogens in relation to circulating testosterone. Neonatal gynecomastia is caused by the action of placental estrogens on neonatal breast tissues, whereas in adolescence, there is an excess of estradiol
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Surgery_Schwartz. disease with associated gynecomastia f. Eunuchoidal state (congenital anorchia) g. Hereditary defects of androgen biosynthesis h. Adrenocorticotropic hormone deficiency 2. Secondary testicular failure a. Trauma b. Orchitis c. Cryptorchidism d. Irradiation C. Renal failure III. Pharmacologic causes IV. Systemic diseases with idiopathic mechanismsthe ovaries and involution of the ducts and alveoli of the breast. The surrounding fibrous connective tissue increases in density, and breast tissues are replaced by adipose tissues (Fig. 17-9D).GynecomastiaGynecomastia refers to an enlarged breast in the male.20 Physi-ologic gynecomastia usually occurs during three phases of life: the neonatal period, adolescence, and senescence. Common to each of these phases is an excess of circulating estrogens in relation to circulating testosterone. Neonatal gynecomastia is caused by the action of placental estrogens on neonatal breast tissues, whereas in adolescence, there is an excess of estradiol
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Surgery_Schwartz_3724
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Surgery_Schwartz
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in relation to circulating testosterone. Neonatal gynecomastia is caused by the action of placental estrogens on neonatal breast tissues, whereas in adolescence, there is an excess of estradiol relative to testosterone, and with senescence, the circulating testosterone level falls, which results in relative hyperestrin-ism. In gynecomastia, the ductal structures of the male breast enlarge, elongate, and branch with a concomitant increase in epithelium. During puberty, the condition often is unilateral and typically occurs between ages 12 and 15 years. In contrast, senescent gynecomastia is usually bilateral. In the nonobese male, breast tissue measuring at least 2 cm in diameter must be present before a diagnosis of gynecomastia may be made. Mammography and ultrasonography are used to differentiate breast tissues. Dominant masses or areas of firmness, irregular-ity, and asymmetry suggest the possibility of a breast cancer, particularly in the older male. Gynecomastia generally does
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Surgery_Schwartz. in relation to circulating testosterone. Neonatal gynecomastia is caused by the action of placental estrogens on neonatal breast tissues, whereas in adolescence, there is an excess of estradiol relative to testosterone, and with senescence, the circulating testosterone level falls, which results in relative hyperestrin-ism. In gynecomastia, the ductal structures of the male breast enlarge, elongate, and branch with a concomitant increase in epithelium. During puberty, the condition often is unilateral and typically occurs between ages 12 and 15 years. In contrast, senescent gynecomastia is usually bilateral. In the nonobese male, breast tissue measuring at least 2 cm in diameter must be present before a diagnosis of gynecomastia may be made. Mammography and ultrasonography are used to differentiate breast tissues. Dominant masses or areas of firmness, irregular-ity, and asymmetry suggest the possibility of a breast cancer, particularly in the older male. Gynecomastia generally does
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Surgery_Schwartz_3725
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Surgery_Schwartz
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breast tissues. Dominant masses or areas of firmness, irregular-ity, and asymmetry suggest the possibility of a breast cancer, particularly in the older male. Gynecomastia generally does not predispose the male breast to cancer. However, the hypoandro-genic state of Klinefelter’s syndrome (XXY), in which gyneco-mastia is usually evident, is associated with an increased risk of breast cancer. Gynecomastia is graded based on the degree of breast enlargement, the position of the nipple with reference to the inframammary fold, and the degree of breast ptosis and skin redundancy: Grade I—mild breast enlargement without skin redundancy; Grade IIa—moderate breast enlargement without skin redundancy; Grade IIb—moderate breast enlargement with skin redundancy; and Grade III—marked breast enlargement with skin redundancy and ptosis.Table 17-1 identifies the pathophysiologic mechanisms that may initiate gynecomastia: estrogen excess states; andro-gen deficiency states; pharmacologic causes; and
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Surgery_Schwartz. breast tissues. Dominant masses or areas of firmness, irregular-ity, and asymmetry suggest the possibility of a breast cancer, particularly in the older male. Gynecomastia generally does not predispose the male breast to cancer. However, the hypoandro-genic state of Klinefelter’s syndrome (XXY), in which gyneco-mastia is usually evident, is associated with an increased risk of breast cancer. Gynecomastia is graded based on the degree of breast enlargement, the position of the nipple with reference to the inframammary fold, and the degree of breast ptosis and skin redundancy: Grade I—mild breast enlargement without skin redundancy; Grade IIa—moderate breast enlargement without skin redundancy; Grade IIb—moderate breast enlargement with skin redundancy; and Grade III—marked breast enlargement with skin redundancy and ptosis.Table 17-1 identifies the pathophysiologic mechanisms that may initiate gynecomastia: estrogen excess states; andro-gen deficiency states; pharmacologic causes; and
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Surgery_Schwartz_3726
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Surgery_Schwartz
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with skin redundancy and ptosis.Table 17-1 identifies the pathophysiologic mechanisms that may initiate gynecomastia: estrogen excess states; andro-gen deficiency states; pharmacologic causes; and idiopathic causes. Estrogen excess results from an increase in the secretion of estradiol by the testicles or by nontesticular tumors, nutri-tional alterations such as protein and fat deprivation, endocrine disorders (hyperthyroidism, hypothyroidism), and hepatic dis-ease (nonalcoholic and alcoholic cirrhosis). Refeeding gyne-comastia is related to the resumption of pituitary gonadotropin secretion after pituitary shutdown. Androgen deficiency may initiate gynecomastia. Concurrently occurring with decreased circulating testosterone levels is an elevated level of circulating testosterone-binding globulin, which results in a reduction of free testosterone. This senescent gynecomastia usually occurs in men age 50 to 70 years. Hypoandrogenic states can be from primary testicular failure or
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Surgery_Schwartz. with skin redundancy and ptosis.Table 17-1 identifies the pathophysiologic mechanisms that may initiate gynecomastia: estrogen excess states; andro-gen deficiency states; pharmacologic causes; and idiopathic causes. Estrogen excess results from an increase in the secretion of estradiol by the testicles or by nontesticular tumors, nutri-tional alterations such as protein and fat deprivation, endocrine disorders (hyperthyroidism, hypothyroidism), and hepatic dis-ease (nonalcoholic and alcoholic cirrhosis). Refeeding gyne-comastia is related to the resumption of pituitary gonadotropin secretion after pituitary shutdown. Androgen deficiency may initiate gynecomastia. Concurrently occurring with decreased circulating testosterone levels is an elevated level of circulating testosterone-binding globulin, which results in a reduction of free testosterone. This senescent gynecomastia usually occurs in men age 50 to 70 years. Hypoandrogenic states can be from primary testicular failure or
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Surgery_Schwartz_3727
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Surgery_Schwartz
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globulin, which results in a reduction of free testosterone. This senescent gynecomastia usually occurs in men age 50 to 70 years. Hypoandrogenic states can be from primary testicular failure or secondary testicular failure. Kline-felter’s syndrome (XXY) is an example of primary testicular failure that is manifested by gynecomastia, hypergonadotropic hypogonadism, and azoospermia. Secondary testicular failure may result from trauma, orchitis, and cryptorchidism. Renal failure, regardless of cause, also may initiate gynecomastia.Pharmacologic causes of gynecomastia include drugs with estrogenic activity (digitalis, estrogens, anabolic steroids, marijuana) or drugs that enhance estrogen synthesis (human chorionic gonadotropin). Drugs that inhibit the action or syn-thesis of testosterone (cimetidine, ketoconazole, phenytoin, spironolactone, antineoplastic agents, diazepam) also have been implicated. Drugs such as reserpine, theophylline, verapamil, tricyclic antidepressants, and
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Surgery_Schwartz. globulin, which results in a reduction of free testosterone. This senescent gynecomastia usually occurs in men age 50 to 70 years. Hypoandrogenic states can be from primary testicular failure or secondary testicular failure. Kline-felter’s syndrome (XXY) is an example of primary testicular failure that is manifested by gynecomastia, hypergonadotropic hypogonadism, and azoospermia. Secondary testicular failure may result from trauma, orchitis, and cryptorchidism. Renal failure, regardless of cause, also may initiate gynecomastia.Pharmacologic causes of gynecomastia include drugs with estrogenic activity (digitalis, estrogens, anabolic steroids, marijuana) or drugs that enhance estrogen synthesis (human chorionic gonadotropin). Drugs that inhibit the action or syn-thesis of testosterone (cimetidine, ketoconazole, phenytoin, spironolactone, antineoplastic agents, diazepam) also have been implicated. Drugs such as reserpine, theophylline, verapamil, tricyclic antidepressants, and
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Surgery_Schwartz_3728
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(cimetidine, ketoconazole, phenytoin, spironolactone, antineoplastic agents, diazepam) also have been implicated. Drugs such as reserpine, theophylline, verapamil, tricyclic antidepressants, and furosemide induce gynecomastia through idiopathic mechanisms.When gynecomastia is caused by androgen deficiency, then testosterone administration may cause regression. When it is caused by medications, then these are discontinued if possi-ble. When endocrine defects are responsible, then these receive specific therapy. As soon as gynecomastia is progressive and does not respond to other treatments, surgical therapy is con-sidered. Techniques include local excision, liposuction or sub-cutaneous mastectomy. Attempts to reverse gynecomastia with danazol have been successful, but the androgenic side effects of the drug are considerable.Brunicardi_Ch17_p0541-p0612.indd 54901/03/19 5:04 PM 550SPECIFIC CONSIDERATIONSPART IIINFECTIOUS AND INFLAMMATORY DISORDERS OF THE BREASTInfections in the
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Surgery_Schwartz. (cimetidine, ketoconazole, phenytoin, spironolactone, antineoplastic agents, diazepam) also have been implicated. Drugs such as reserpine, theophylline, verapamil, tricyclic antidepressants, and furosemide induce gynecomastia through idiopathic mechanisms.When gynecomastia is caused by androgen deficiency, then testosterone administration may cause regression. When it is caused by medications, then these are discontinued if possi-ble. When endocrine defects are responsible, then these receive specific therapy. As soon as gynecomastia is progressive and does not respond to other treatments, surgical therapy is con-sidered. Techniques include local excision, liposuction or sub-cutaneous mastectomy. Attempts to reverse gynecomastia with danazol have been successful, but the androgenic side effects of the drug are considerable.Brunicardi_Ch17_p0541-p0612.indd 54901/03/19 5:04 PM 550SPECIFIC CONSIDERATIONSPART IIINFECTIOUS AND INFLAMMATORY DISORDERS OF THE BREASTInfections in the
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Surgery_Schwartz_3729
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effects of the drug are considerable.Brunicardi_Ch17_p0541-p0612.indd 54901/03/19 5:04 PM 550SPECIFIC CONSIDERATIONSPART IIINFECTIOUS AND INFLAMMATORY DISORDERS OF THE BREASTInfections in the postpartum period remain proportionately the most common time for breast infections to occur. Infections of the breast unrelated to lactation are proportionately less com-mon, however, are still a relatively common presentation to breast specialists. The latter are classified as intrinsic (second-ary to abnormalities in the breast) or extrinsic (secondary to an infection in an adjacent structure, e.g., skin, thoracic cavity) the most common being probably periductal mastitis and infected sebaceous cysts, respectively.Bacterial InfectionStaphylococcus aureus and Streptococcus species are the organisms most frequently recovered from nipple discharge from an infected breast.17 Typically breast abscesses are seen in staphylococcal infections and present with point tenderness, erythema, and
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Surgery_Schwartz. effects of the drug are considerable.Brunicardi_Ch17_p0541-p0612.indd 54901/03/19 5:04 PM 550SPECIFIC CONSIDERATIONSPART IIINFECTIOUS AND INFLAMMATORY DISORDERS OF THE BREASTInfections in the postpartum period remain proportionately the most common time for breast infections to occur. Infections of the breast unrelated to lactation are proportionately less com-mon, however, are still a relatively common presentation to breast specialists. The latter are classified as intrinsic (second-ary to abnormalities in the breast) or extrinsic (secondary to an infection in an adjacent structure, e.g., skin, thoracic cavity) the most common being probably periductal mastitis and infected sebaceous cysts, respectively.Bacterial InfectionStaphylococcus aureus and Streptococcus species are the organisms most frequently recovered from nipple discharge from an infected breast.17 Typically breast abscesses are seen in staphylococcal infections and present with point tenderness, erythema, and
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Surgery_Schwartz_3730
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Surgery_Schwartz
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organisms most frequently recovered from nipple discharge from an infected breast.17 Typically breast abscesses are seen in staphylococcal infections and present with point tenderness, erythema, and hyperthermia. When these abscesses are related to lactation they usually occur within the first few weeks of breastfeeding. If there is progression of a staphylococcal infec-tion, this may result in subcutaneous, subareolar, interlobular (periductal), and retromammary abscesses (unicentric or multi-centric). Previously almost all breast abscesses were treated by operative incision and drainage, but now the initial approach is antibiotics and repeated aspiration of the abscess, usually ultra-sound-guided aspiration.21 Operative drainage is now reserved for those cases that do not resolve with repeated aspiration and antibiotic therapy or cases in which there is some other indica-tion for incision and drainage (e.g., thinning or necrosis of the overlying skin). Preoperative ultrasonography
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Surgery_Schwartz. organisms most frequently recovered from nipple discharge from an infected breast.17 Typically breast abscesses are seen in staphylococcal infections and present with point tenderness, erythema, and hyperthermia. When these abscesses are related to lactation they usually occur within the first few weeks of breastfeeding. If there is progression of a staphylococcal infec-tion, this may result in subcutaneous, subareolar, interlobular (periductal), and retromammary abscesses (unicentric or multi-centric). Previously almost all breast abscesses were treated by operative incision and drainage, but now the initial approach is antibiotics and repeated aspiration of the abscess, usually ultra-sound-guided aspiration.21 Operative drainage is now reserved for those cases that do not resolve with repeated aspiration and antibiotic therapy or cases in which there is some other indica-tion for incision and drainage (e.g., thinning or necrosis of the overlying skin). Preoperative ultrasonography
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Surgery_Schwartz_3731
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Surgery_Schwartz
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repeated aspiration and antibiotic therapy or cases in which there is some other indica-tion for incision and drainage (e.g., thinning or necrosis of the overlying skin). Preoperative ultrasonography is effective in delineating the required extent of the drainage procedure. While staphylococcal infections tend to be more localized and may be situated deep in the breast tissues, streptococcal infections usually present with diffuse superficial involvement. They are treated with local wound care, including application of warm compresses, and the administration of IV antibiotics (penicillins or cephalosporins). Breast infections may be chronic, possibly with recurrent abscess formation. In this situation, cultures are performed to identify acid-fast bacilli, anaerobic and aerobic bacteria, and fungi. Uncommon organisms may be encountered, and long-term antibiotic therapy may be required.Biopsy of the abscess cavity wall should be considered at the time of incision and drainage to rule
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Surgery_Schwartz. repeated aspiration and antibiotic therapy or cases in which there is some other indica-tion for incision and drainage (e.g., thinning or necrosis of the overlying skin). Preoperative ultrasonography is effective in delineating the required extent of the drainage procedure. While staphylococcal infections tend to be more localized and may be situated deep in the breast tissues, streptococcal infections usually present with diffuse superficial involvement. They are treated with local wound care, including application of warm compresses, and the administration of IV antibiotics (penicillins or cephalosporins). Breast infections may be chronic, possibly with recurrent abscess formation. In this situation, cultures are performed to identify acid-fast bacilli, anaerobic and aerobic bacteria, and fungi. Uncommon organisms may be encountered, and long-term antibiotic therapy may be required.Biopsy of the abscess cavity wall should be considered at the time of incision and drainage to rule
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Surgery_Schwartz_3732
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Surgery_Schwartz
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and fungi. Uncommon organisms may be encountered, and long-term antibiotic therapy may be required.Biopsy of the abscess cavity wall should be considered at the time of incision and drainage to rule out underlying breast cancer in patients where antibiotics and drainage have been ineffective.Nowadays hospital-acquired puerperal infections of the breast are much less common, but nursing women who pres-ent with milk stasis or noninfectious inflammation may still develop this problem. Epidemic puerperal mastitis is initiated by highly virulent strains of methicillin-resistant S aureus that are transmitted via the suckling neonate and may result in sub-stantial morbidity and occasional mortality. Purulent fluid may be expressed from the nipple. In this circumstance, breastfeed-ing is stopped, antibiotics are started, and surgical therapy is initiated. Nonepidemic (sporadic) puerperal mastitis refers to involvement of the interlobular connective tissue of the breast by an infectious
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Surgery_Schwartz. and fungi. Uncommon organisms may be encountered, and long-term antibiotic therapy may be required.Biopsy of the abscess cavity wall should be considered at the time of incision and drainage to rule out underlying breast cancer in patients where antibiotics and drainage have been ineffective.Nowadays hospital-acquired puerperal infections of the breast are much less common, but nursing women who pres-ent with milk stasis or noninfectious inflammation may still develop this problem. Epidemic puerperal mastitis is initiated by highly virulent strains of methicillin-resistant S aureus that are transmitted via the suckling neonate and may result in sub-stantial morbidity and occasional mortality. Purulent fluid may be expressed from the nipple. In this circumstance, breastfeed-ing is stopped, antibiotics are started, and surgical therapy is initiated. Nonepidemic (sporadic) puerperal mastitis refers to involvement of the interlobular connective tissue of the breast by an infectious
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Surgery_Schwartz_3733
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Surgery_Schwartz
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antibiotics are started, and surgical therapy is initiated. Nonepidemic (sporadic) puerperal mastitis refers to involvement of the interlobular connective tissue of the breast by an infectious process. The patient develops nipple fissuring and milk stasis, which initiates a retrograde bacterial infection. Emptying of the breast using breast suction pumps shortens the duration of symptoms and reduces the incidence of recurrences. The addition of antibiotic therapy results in a satisfactory out-come in >95% of cases.Zuska’s disease, also called recurrent periductal mastitis, is a condition of recurrent retroareolar infections and abscesses.22,23 Smoking has been implicated as a risk factor for this condition.24,25 This syndrome is managed symptomatically by antibiotics coupled with incision and drainage as necessary. Attempts to obtain durable long-term control by wide debride-ment of chronically infected tissue and/or terminal duct resec-tion have been reported and can be curative, but
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Surgery_Schwartz. antibiotics are started, and surgical therapy is initiated. Nonepidemic (sporadic) puerperal mastitis refers to involvement of the interlobular connective tissue of the breast by an infectious process. The patient develops nipple fissuring and milk stasis, which initiates a retrograde bacterial infection. Emptying of the breast using breast suction pumps shortens the duration of symptoms and reduces the incidence of recurrences. The addition of antibiotic therapy results in a satisfactory out-come in >95% of cases.Zuska’s disease, also called recurrent periductal mastitis, is a condition of recurrent retroareolar infections and abscesses.22,23 Smoking has been implicated as a risk factor for this condition.24,25 This syndrome is managed symptomatically by antibiotics coupled with incision and drainage as necessary. Attempts to obtain durable long-term control by wide debride-ment of chronically infected tissue and/or terminal duct resec-tion have been reported and can be curative, but
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Surgery_Schwartz_3734
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Surgery_Schwartz
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and drainage as necessary. Attempts to obtain durable long-term control by wide debride-ment of chronically infected tissue and/or terminal duct resec-tion have been reported and can be curative, but they can also be frustrated by postoperative infections.26Mycotic InfectionsFungal infections of the breast are rare and usually involve blas-tomycosis or sporotrichosis.27 Intraoral fungi that are inoculated into the breast tissue by the suckling infant initiate these infec-tions, which present as mammary abscesses in close proxim-ity to the nipple-areola complex. Pus mixed with blood may be expressed from sinus tracts. Antifungal agents can be adminis-tered for the treatment of systemic (noncutaneous) infections. This therapy generally eliminates the necessity of surgical inter-vention, but occasionally drainage of an abscess, or even partial mastectomy, may be necessary to eradicate a persistent fungal infection. Candida albicans affecting the skin of the breast presents as
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Surgery_Schwartz. and drainage as necessary. Attempts to obtain durable long-term control by wide debride-ment of chronically infected tissue and/or terminal duct resec-tion have been reported and can be curative, but they can also be frustrated by postoperative infections.26Mycotic InfectionsFungal infections of the breast are rare and usually involve blas-tomycosis or sporotrichosis.27 Intraoral fungi that are inoculated into the breast tissue by the suckling infant initiate these infec-tions, which present as mammary abscesses in close proxim-ity to the nipple-areola complex. Pus mixed with blood may be expressed from sinus tracts. Antifungal agents can be adminis-tered for the treatment of systemic (noncutaneous) infections. This therapy generally eliminates the necessity of surgical inter-vention, but occasionally drainage of an abscess, or even partial mastectomy, may be necessary to eradicate a persistent fungal infection. Candida albicans affecting the skin of the breast presents as
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Surgery_Schwartz_3735
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but occasionally drainage of an abscess, or even partial mastectomy, may be necessary to eradicate a persistent fungal infection. Candida albicans affecting the skin of the breast presents as erythematous, scaly lesions of the inframammary or axillary folds. Scrapings from the lesions demonstrate fungal elements (filaments and binding cells). Therapy involves the removal of predisposing factors such as maceration and the topi-cal application of nystatin.Hidradenitis SuppurativaHidradenitis suppurativa of the nipple-areola complex or axilla is a chronic inflammatory condition that originates within the accessory areolar glands of Montgomery or within the axillary sebaceous glands.27 Women with chronic acne are predisposed to developing hidradenitis. When located in and about the nipple-areola complex, this disease may mimic other chronic inflammatory states, Paget’s disease of the nipple, or invasive breast cancer. Involvement of the axillary skin is often multifo-cal and contiguous.
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Surgery_Schwartz. but occasionally drainage of an abscess, or even partial mastectomy, may be necessary to eradicate a persistent fungal infection. Candida albicans affecting the skin of the breast presents as erythematous, scaly lesions of the inframammary or axillary folds. Scrapings from the lesions demonstrate fungal elements (filaments and binding cells). Therapy involves the removal of predisposing factors such as maceration and the topi-cal application of nystatin.Hidradenitis SuppurativaHidradenitis suppurativa of the nipple-areola complex or axilla is a chronic inflammatory condition that originates within the accessory areolar glands of Montgomery or within the axillary sebaceous glands.27 Women with chronic acne are predisposed to developing hidradenitis. When located in and about the nipple-areola complex, this disease may mimic other chronic inflammatory states, Paget’s disease of the nipple, or invasive breast cancer. Involvement of the axillary skin is often multifo-cal and contiguous.
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complex, this disease may mimic other chronic inflammatory states, Paget’s disease of the nipple, or invasive breast cancer. Involvement of the axillary skin is often multifo-cal and contiguous. Antibiotic therapy with incision and drain-age of fluctuant areas is appropriate treatment. Excision of the involved areas may be required. Large areas of skin loss may necessitate coverage with advancement flaps or split-thickness skin grafts.Mondor’s DiseaseMondor’s disease is a variant of thrombophlebitis that involves the superficial veins of the anterior chest wall and breast.28 In 1939, Mondor described the condition as “string phlebitis,” a thrombosed vein presenting as a tender, cord-like structure.29 Frequently involved veins include the lateral thoracic vein, the thoracoepigastric vein, and, less commonly, the superficial epi-gastric vein. Typically, a woman presents with acute pain in the lateral aspect of the breast or the anterior chest wall. A ten-der, firm cord is found to
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Surgery_Schwartz. complex, this disease may mimic other chronic inflammatory states, Paget’s disease of the nipple, or invasive breast cancer. Involvement of the axillary skin is often multifo-cal and contiguous. Antibiotic therapy with incision and drain-age of fluctuant areas is appropriate treatment. Excision of the involved areas may be required. Large areas of skin loss may necessitate coverage with advancement flaps or split-thickness skin grafts.Mondor’s DiseaseMondor’s disease is a variant of thrombophlebitis that involves the superficial veins of the anterior chest wall and breast.28 In 1939, Mondor described the condition as “string phlebitis,” a thrombosed vein presenting as a tender, cord-like structure.29 Frequently involved veins include the lateral thoracic vein, the thoracoepigastric vein, and, less commonly, the superficial epi-gastric vein. Typically, a woman presents with acute pain in the lateral aspect of the breast or the anterior chest wall. A ten-der, firm cord is found to
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and, less commonly, the superficial epi-gastric vein. Typically, a woman presents with acute pain in the lateral aspect of the breast or the anterior chest wall. A ten-der, firm cord is found to follow the distribution of one of the major superficial veins. Rarely, the presentation is bilateral, and most women have no evidence of thrombophlebitis in other ana-tomic sites. This benign, self-limited disorder is not indicative of a cancer. When the diagnosis is uncertain, or when a mass is present near the tender cord, biopsy is indicated. Therapy for Mondor’s disease includes the liberal use of anti-inflammatory medications and application of warm compresses along the symptomatic vein. The process usually resolves within 4 to 6 weeks. When symptoms persist or are refractory to therapy, excision of the involved vein segment may be considered.Brunicardi_Ch17_p0541-p0612.indd 55001/03/19 5:04 PM 551THE BREASTCHAPTER 17COMMON BENIGN DISORDERS AND DISEASES OF THE BREASTBenign breast
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Surgery_Schwartz. and, less commonly, the superficial epi-gastric vein. Typically, a woman presents with acute pain in the lateral aspect of the breast or the anterior chest wall. A ten-der, firm cord is found to follow the distribution of one of the major superficial veins. Rarely, the presentation is bilateral, and most women have no evidence of thrombophlebitis in other ana-tomic sites. This benign, self-limited disorder is not indicative of a cancer. When the diagnosis is uncertain, or when a mass is present near the tender cord, biopsy is indicated. Therapy for Mondor’s disease includes the liberal use of anti-inflammatory medications and application of warm compresses along the symptomatic vein. The process usually resolves within 4 to 6 weeks. When symptoms persist or are refractory to therapy, excision of the involved vein segment may be considered.Brunicardi_Ch17_p0541-p0612.indd 55001/03/19 5:04 PM 551THE BREASTCHAPTER 17COMMON BENIGN DISORDERS AND DISEASES OF THE BREASTBenign breast
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of the involved vein segment may be considered.Brunicardi_Ch17_p0541-p0612.indd 55001/03/19 5:04 PM 551THE BREASTCHAPTER 17COMMON BENIGN DISORDERS AND DISEASES OF THE BREASTBenign breast disorders and diseases encompass a wide range of clinical and pathologic entities. Surgeons require an in-depth understanding of benign breast disorders and diseases so that clear explanations may be given to affected women, appropriate treat-ment is instituted, and unnecessary long-term follow up is avoided.Aberrations of Normal Development and InvolutionThe basic principles underlying the aberrations of normal devel-opment and involution (ANDI) classification of benign breast conditions are the following: (a) benign breast disorders and diseases are related to the normal processes of reproductive life and to involution; (b) there is a spectrum of breast conditions that ranges from normal to disorder to disease; and (c) the ANDI classification encompasses all aspects of the breast condition,
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Surgery_Schwartz. of the involved vein segment may be considered.Brunicardi_Ch17_p0541-p0612.indd 55001/03/19 5:04 PM 551THE BREASTCHAPTER 17COMMON BENIGN DISORDERS AND DISEASES OF THE BREASTBenign breast disorders and diseases encompass a wide range of clinical and pathologic entities. Surgeons require an in-depth understanding of benign breast disorders and diseases so that clear explanations may be given to affected women, appropriate treat-ment is instituted, and unnecessary long-term follow up is avoided.Aberrations of Normal Development and InvolutionThe basic principles underlying the aberrations of normal devel-opment and involution (ANDI) classification of benign breast conditions are the following: (a) benign breast disorders and diseases are related to the normal processes of reproductive life and to involution; (b) there is a spectrum of breast conditions that ranges from normal to disorder to disease; and (c) the ANDI classification encompasses all aspects of the breast condition,
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life and to involution; (b) there is a spectrum of breast conditions that ranges from normal to disorder to disease; and (c) the ANDI classification encompasses all aspects of the breast condition, including pathogenesis and the degree of abnormality.30 The horizontal component of Table 17-2 defines ANDI along a spectrum from normal, to mild abnormality (disorder), to severe abnormality (disease). The vertical component indi-cates the period during which the condition develops.Early Reproductive Years. Fibroadenomas are seen and pres-ent symptomatically predominantly in younger women age 15 to 25 years (Fig. 17-10).31 Fibroadenomas usually grow to 1 or 2 cm in diameter and then are stable but may grow to a larger size. Small fibroadenomas (≤1 cm in size) are considered nor-mal, whereas larger fibroadenomas (≤3 cm) are disorders, and giant fibroadenomas (>3 cm) are disease. Similarly, multiple fibroadenomas (more than five lesions in one breast) are very uncommon and are considered
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Surgery_Schwartz. life and to involution; (b) there is a spectrum of breast conditions that ranges from normal to disorder to disease; and (c) the ANDI classification encompasses all aspects of the breast condition, including pathogenesis and the degree of abnormality.30 The horizontal component of Table 17-2 defines ANDI along a spectrum from normal, to mild abnormality (disorder), to severe abnormality (disease). The vertical component indi-cates the period during which the condition develops.Early Reproductive Years. Fibroadenomas are seen and pres-ent symptomatically predominantly in younger women age 15 to 25 years (Fig. 17-10).31 Fibroadenomas usually grow to 1 or 2 cm in diameter and then are stable but may grow to a larger size. Small fibroadenomas (≤1 cm in size) are considered nor-mal, whereas larger fibroadenomas (≤3 cm) are disorders, and giant fibroadenomas (>3 cm) are disease. Similarly, multiple fibroadenomas (more than five lesions in one breast) are very uncommon and are considered
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larger fibroadenomas (≤3 cm) are disorders, and giant fibroadenomas (>3 cm) are disease. Similarly, multiple fibroadenomas (more than five lesions in one breast) are very uncommon and are considered disease. It is noted that with the introduction of mammographic screening, asymptomatic 4Table 17-2ANDI classification of benign breast disorders NORMALDISORDERDISEASEEarly reproductive years (age 15–25 y) Lobular developmentStromal developmentFibroadenomaAdolescent hypertrophyGiant fibroadenomaGigantomastia Nipple eversionNipple inversionSubareolar abscess Mammary duct fistulaLater reproductive years (age 25–40 y)Cyclical changes of menstruationCyclical mastalgiaIncapacitating mastalgia Nodularity Epithelial hyperplasia of pregnancyBloody nipple discharge Involution (age 35–55 y)Lobular involutionMacrocysts— Sclerosing lesions Duct involution DilatationDuct ectasiaPeriductal mastitis SclerosisNipple retraction— Epithelial turnoverEpithelial hyperplasiaEpithelial hyperplasia with
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Surgery_Schwartz. larger fibroadenomas (≤3 cm) are disorders, and giant fibroadenomas (>3 cm) are disease. Similarly, multiple fibroadenomas (more than five lesions in one breast) are very uncommon and are considered disease. It is noted that with the introduction of mammographic screening, asymptomatic 4Table 17-2ANDI classification of benign breast disorders NORMALDISORDERDISEASEEarly reproductive years (age 15–25 y) Lobular developmentStromal developmentFibroadenomaAdolescent hypertrophyGiant fibroadenomaGigantomastia Nipple eversionNipple inversionSubareolar abscess Mammary duct fistulaLater reproductive years (age 25–40 y)Cyclical changes of menstruationCyclical mastalgiaIncapacitating mastalgia Nodularity Epithelial hyperplasia of pregnancyBloody nipple discharge Involution (age 35–55 y)Lobular involutionMacrocysts— Sclerosing lesions Duct involution DilatationDuct ectasiaPeriductal mastitis SclerosisNipple retraction— Epithelial turnoverEpithelial hyperplasiaEpithelial hyperplasia with
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lesions Duct involution DilatationDuct ectasiaPeriductal mastitis SclerosisNipple retraction— Epithelial turnoverEpithelial hyperplasiaEpithelial hyperplasia with atypiaANDI = aberrations of normal development and involution.Reproduced with permission from Mansel RE, Webster D, Sweetland H: Hughes, Mansel & Webster’s Benign Disorders and Diseases of the Breast, 3rd ed. London: Elsevier/Saunders; 2009.Figure 17-10. Fibroadenoma (40x). These benign tumors are typi-cally well circumscribed and are comprised of both stromal and glandular elements. (Used with permission from Dr. Sindhu Menon, Consultant Histopathologist and Dr. Rahul Deb, Consultant Histopathologist and Lead Breast Pathologist, Royal Derby Hospital, Derby, UK.)fibroadenomas are sometimes found in an older screened popu-lation. The precise etiology of adolescent breast hypertrophy is unknown. A spectrum of changes from limited to massive stro-mal hyperplasia (gigantomastia) is seen. Nipple inversion is a disorder of
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Surgery_Schwartz. lesions Duct involution DilatationDuct ectasiaPeriductal mastitis SclerosisNipple retraction— Epithelial turnoverEpithelial hyperplasiaEpithelial hyperplasia with atypiaANDI = aberrations of normal development and involution.Reproduced with permission from Mansel RE, Webster D, Sweetland H: Hughes, Mansel & Webster’s Benign Disorders and Diseases of the Breast, 3rd ed. London: Elsevier/Saunders; 2009.Figure 17-10. Fibroadenoma (40x). These benign tumors are typi-cally well circumscribed and are comprised of both stromal and glandular elements. (Used with permission from Dr. Sindhu Menon, Consultant Histopathologist and Dr. Rahul Deb, Consultant Histopathologist and Lead Breast Pathologist, Royal Derby Hospital, Derby, UK.)fibroadenomas are sometimes found in an older screened popu-lation. The precise etiology of adolescent breast hypertrophy is unknown. A spectrum of changes from limited to massive stro-mal hyperplasia (gigantomastia) is seen. Nipple inversion is a disorder of
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The precise etiology of adolescent breast hypertrophy is unknown. A spectrum of changes from limited to massive stro-mal hyperplasia (gigantomastia) is seen. Nipple inversion is a disorder of development of the major ducts, which prevents nor-mal protrusion of the nipple. Mammary duct fistulas arise when nipple inversion predisposes to major duct obstruction, leading to recurrent subareolar abscess and mammary duct fistula.Brunicardi_Ch17_p0541-p0612.indd 55101/03/19 5:04 PM 552SPECIFIC CONSIDERATIONSPART IIABFigure 17-11. A. Ductal epithelial hyperplasia. The irregular intra-cellular spaces and variable cell nuclei distinguish this process from carcinoma in situ. B. Lobular hyperplasia. The presence of alveo-lar lumina and incomplete distention distinguish this process from carcinoma in situ. (Used with permission from Dr. R.L. Hackett.)Table 17-3Cancer risk associated with benign breast disorders and in situ carcinoma of the breastABNORMALITYRELATIVE RISKNonproliferative lesions
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Surgery_Schwartz. The precise etiology of adolescent breast hypertrophy is unknown. A spectrum of changes from limited to massive stro-mal hyperplasia (gigantomastia) is seen. Nipple inversion is a disorder of development of the major ducts, which prevents nor-mal protrusion of the nipple. Mammary duct fistulas arise when nipple inversion predisposes to major duct obstruction, leading to recurrent subareolar abscess and mammary duct fistula.Brunicardi_Ch17_p0541-p0612.indd 55101/03/19 5:04 PM 552SPECIFIC CONSIDERATIONSPART IIABFigure 17-11. A. Ductal epithelial hyperplasia. The irregular intra-cellular spaces and variable cell nuclei distinguish this process from carcinoma in situ. B. Lobular hyperplasia. The presence of alveo-lar lumina and incomplete distention distinguish this process from carcinoma in situ. (Used with permission from Dr. R.L. Hackett.)Table 17-3Cancer risk associated with benign breast disorders and in situ carcinoma of the breastABNORMALITYRELATIVE RISKNonproliferative lesions
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in situ. (Used with permission from Dr. R.L. Hackett.)Table 17-3Cancer risk associated with benign breast disorders and in situ carcinoma of the breastABNORMALITYRELATIVE RISKNonproliferative lesions of the breastNo increased riskSclerosing adenosisNo increased riskIntraductal papillomaNo increased riskFlorid hyperplasia1.5 to 2-foldAtypical lobular hyperplasia4-foldAtypical ductal hyperplasia4-foldDuctal involvement by cells of atypical ductal hyperplasia7-foldLobular carcinoma in situ10-foldDuctal carcinoma in situ10-foldData from Dupont WD, Page DL. Risk factors for breast cancer in women with proliferative breast disease, N Engl J Med. 1985 Jan 17; 312(3):146-151.Table 17-4Classification of benign breast disordersNonproliferative disorders of the breast Cysts and apocrine metaplasia Duct ectasia Mild ductal epithelial hyperplasia Calcifications Fibroadenoma and related lesionsProliferative breast disorders without atypia Sclerosing adenosis Radial and complex sclerosing
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Surgery_Schwartz. in situ. (Used with permission from Dr. R.L. Hackett.)Table 17-3Cancer risk associated with benign breast disorders and in situ carcinoma of the breastABNORMALITYRELATIVE RISKNonproliferative lesions of the breastNo increased riskSclerosing adenosisNo increased riskIntraductal papillomaNo increased riskFlorid hyperplasia1.5 to 2-foldAtypical lobular hyperplasia4-foldAtypical ductal hyperplasia4-foldDuctal involvement by cells of atypical ductal hyperplasia7-foldLobular carcinoma in situ10-foldDuctal carcinoma in situ10-foldData from Dupont WD, Page DL. Risk factors for breast cancer in women with proliferative breast disease, N Engl J Med. 1985 Jan 17; 312(3):146-151.Table 17-4Classification of benign breast disordersNonproliferative disorders of the breast Cysts and apocrine metaplasia Duct ectasia Mild ductal epithelial hyperplasia Calcifications Fibroadenoma and related lesionsProliferative breast disorders without atypia Sclerosing adenosis Radial and complex sclerosing
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ectasia Mild ductal epithelial hyperplasia Calcifications Fibroadenoma and related lesionsProliferative breast disorders without atypia Sclerosing adenosis Radial and complex sclerosing lesions Ductal epithelial hyperplasia Intraductal papillomasAtypical proliferative lesions Atypical lobular hyperplasia Atypical ductal hyperplasiaData from Godfrey SE: Is fibrocystic disease of the breast precancerous? Arch Pathol Lab Med. 1986 Nov;110(11):991.include ductal and lobular hyperplasia, both of which display some features of carcinoma in situ. Women with atypical ductal or lobular hyperplasia have a fourfold increase in breast cancer risk (Table 17-3).Pathology of Nonproliferative DisordersOf paramount importance for the optimal management of benign breast disorders and diseases is the histologic differentia-tion of benign, atypical, and malignant changes.32,33 Determin-ing the clinical significance of these changes is a problem that is compounded by inconsistent nomenclature. The
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Surgery_Schwartz. ectasia Mild ductal epithelial hyperplasia Calcifications Fibroadenoma and related lesionsProliferative breast disorders without atypia Sclerosing adenosis Radial and complex sclerosing lesions Ductal epithelial hyperplasia Intraductal papillomasAtypical proliferative lesions Atypical lobular hyperplasia Atypical ductal hyperplasiaData from Godfrey SE: Is fibrocystic disease of the breast precancerous? Arch Pathol Lab Med. 1986 Nov;110(11):991.include ductal and lobular hyperplasia, both of which display some features of carcinoma in situ. Women with atypical ductal or lobular hyperplasia have a fourfold increase in breast cancer risk (Table 17-3).Pathology of Nonproliferative DisordersOf paramount importance for the optimal management of benign breast disorders and diseases is the histologic differentia-tion of benign, atypical, and malignant changes.32,33 Determin-ing the clinical significance of these changes is a problem that is compounded by inconsistent nomenclature. The
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histologic differentia-tion of benign, atypical, and malignant changes.32,33 Determin-ing the clinical significance of these changes is a problem that is compounded by inconsistent nomenclature. The classifica-tion system originally developed by Page separates the various types of benign breast disorders and diseases into three clini-cally relevant groups: nonproliferative disorders, proliferative disorders without atypia, and proliferative disorders with atypia (Table 17-4). Nonproliferative disorders of the breast account for 70% of benign breast conditions and carry no increased risk Later Reproductive Years. Cyclical mastalgia and nodular-ity usually are associated with premenstrual enlargement of the breast and are regarded as normal. Cyclical pronounced mastal-gia and severe painful nodularity are viewed differently than are physiologic discomfort and lumpiness. Painful nodularity that persists for >1 week of the menstrual cycle is considered a disor-der. In epithelial
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Surgery_Schwartz. histologic differentia-tion of benign, atypical, and malignant changes.32,33 Determin-ing the clinical significance of these changes is a problem that is compounded by inconsistent nomenclature. The classifica-tion system originally developed by Page separates the various types of benign breast disorders and diseases into three clini-cally relevant groups: nonproliferative disorders, proliferative disorders without atypia, and proliferative disorders with atypia (Table 17-4). Nonproliferative disorders of the breast account for 70% of benign breast conditions and carry no increased risk Later Reproductive Years. Cyclical mastalgia and nodular-ity usually are associated with premenstrual enlargement of the breast and are regarded as normal. Cyclical pronounced mastal-gia and severe painful nodularity are viewed differently than are physiologic discomfort and lumpiness. Painful nodularity that persists for >1 week of the menstrual cycle is considered a disor-der. In epithelial
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painful nodularity are viewed differently than are physiologic discomfort and lumpiness. Painful nodularity that persists for >1 week of the menstrual cycle is considered a disor-der. In epithelial hyperplasia of pregnancy, papillary projections sometimes give rise to bilateral bloody nipple discharge.Involution. Involution of lobular epithelium is dependent on the specialized stroma around it. However, an integrated invo-lution of breast stroma and epithelium is not always seen, and disorders of the process are common. When the stroma invo-lutes too quickly, alveoli remain and form microcysts, which are precursors of macrocysts. The macrocysts are common, often subclinical, and do not require specific treatment. Sclerosing adenosis is considered a disorder of both the proliferative and the involutional phases of the breast cycle. Duct ectasia (dilated ducts) and periductal mastitis are other important components of the ANDI classification. Periductal fibrosis is a sequela of
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Surgery_Schwartz. painful nodularity are viewed differently than are physiologic discomfort and lumpiness. Painful nodularity that persists for >1 week of the menstrual cycle is considered a disor-der. In epithelial hyperplasia of pregnancy, papillary projections sometimes give rise to bilateral bloody nipple discharge.Involution. Involution of lobular epithelium is dependent on the specialized stroma around it. However, an integrated invo-lution of breast stroma and epithelium is not always seen, and disorders of the process are common. When the stroma invo-lutes too quickly, alveoli remain and form microcysts, which are precursors of macrocysts. The macrocysts are common, often subclinical, and do not require specific treatment. Sclerosing adenosis is considered a disorder of both the proliferative and the involutional phases of the breast cycle. Duct ectasia (dilated ducts) and periductal mastitis are other important components of the ANDI classification. Periductal fibrosis is a sequela of
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and the involutional phases of the breast cycle. Duct ectasia (dilated ducts) and periductal mastitis are other important components of the ANDI classification. Periductal fibrosis is a sequela of periductal mastitis and may result in nipple retraction. About 60% of women ≥70 years of age exhibit some degree of epi-thelial hyperplasia (Fig. 17-11). Atypical proliferative diseases Brunicardi_Ch17_p0541-p0612.indd 55201/03/19 5:04 PM 553THE BREASTCHAPTER 17for the development of breast cancer. This category includes cysts, duct ectasia, periductal mastitis, calcifications, fibroad-enomas, and related disorders.Breast macrocysts are an involutional disorder, have a high frequency of occurrence, and are often multiple. Duct ecta-sia is a clinical syndrome characterized by dilated subareolar ducts that are palpable and often associated with thick nipple discharge. Haagensen regarded duct ectasia as a primary event that led to stagnation of secretions, epithelial ulceration, and leakage
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Surgery_Schwartz. and the involutional phases of the breast cycle. Duct ectasia (dilated ducts) and periductal mastitis are other important components of the ANDI classification. Periductal fibrosis is a sequela of periductal mastitis and may result in nipple retraction. About 60% of women ≥70 years of age exhibit some degree of epi-thelial hyperplasia (Fig. 17-11). Atypical proliferative diseases Brunicardi_Ch17_p0541-p0612.indd 55201/03/19 5:04 PM 553THE BREASTCHAPTER 17for the development of breast cancer. This category includes cysts, duct ectasia, periductal mastitis, calcifications, fibroad-enomas, and related disorders.Breast macrocysts are an involutional disorder, have a high frequency of occurrence, and are often multiple. Duct ecta-sia is a clinical syndrome characterized by dilated subareolar ducts that are palpable and often associated with thick nipple discharge. Haagensen regarded duct ectasia as a primary event that led to stagnation of secretions, epithelial ulceration, and leakage
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ducts that are palpable and often associated with thick nipple discharge. Haagensen regarded duct ectasia as a primary event that led to stagnation of secretions, epithelial ulceration, and leakage of duct secretions (containing chemically irritating fatty acids) into periductal tissue.34 This sequence was thought to pro-duce a local inflammatory process with periductal fibrosis and subsequent nipple retraction. An alternative theory considers periductal mastitis to be the primary process, which leads to weakening of the ducts and secondary dilatation. It is possible that both processes occur and together explain the wide spec-trum of problems seen, which include nipple discharge, nipple retraction, inflammatory masses, and abscesses.Calcium deposits are frequently encountered in the breast. Most are benign and are caused by cellular secretions and debris or by trauma and inflammation. Calcifications that are associated with cancer include microcalcifications, which vary in shape and
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Surgery_Schwartz. ducts that are palpable and often associated with thick nipple discharge. Haagensen regarded duct ectasia as a primary event that led to stagnation of secretions, epithelial ulceration, and leakage of duct secretions (containing chemically irritating fatty acids) into periductal tissue.34 This sequence was thought to pro-duce a local inflammatory process with periductal fibrosis and subsequent nipple retraction. An alternative theory considers periductal mastitis to be the primary process, which leads to weakening of the ducts and secondary dilatation. It is possible that both processes occur and together explain the wide spec-trum of problems seen, which include nipple discharge, nipple retraction, inflammatory masses, and abscesses.Calcium deposits are frequently encountered in the breast. Most are benign and are caused by cellular secretions and debris or by trauma and inflammation. Calcifications that are associated with cancer include microcalcifications, which vary in shape and
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Most are benign and are caused by cellular secretions and debris or by trauma and inflammation. Calcifications that are associated with cancer include microcalcifications, which vary in shape and density and are <0.5 mm in size, and fine, linear calcifications, which may show branching. Fibroadenomas have abundant stroma with histologically normal cellular elements. They show hormonal dependence similar to that of normal breast lobules in that they lactate during pregnancy and invo-lute in the postmenopausal period. Adenomas of the breast are well circumscribed and are composed of benign epithelium with sparse stroma, which is the histologic feature that differentiates them from fibroadenomas. They may be divided into tubular adenomas and lactating adenomas. Tubular adenomas are seen in young nonpregnant women, whereas lactating adenomas are seen during pregnancy or during the postpartum period. Ham-artomas are discrete breast tumors that are usually 2 to 4 cm in diameter, firm, and
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Surgery_Schwartz. Most are benign and are caused by cellular secretions and debris or by trauma and inflammation. Calcifications that are associated with cancer include microcalcifications, which vary in shape and density and are <0.5 mm in size, and fine, linear calcifications, which may show branching. Fibroadenomas have abundant stroma with histologically normal cellular elements. They show hormonal dependence similar to that of normal breast lobules in that they lactate during pregnancy and invo-lute in the postmenopausal period. Adenomas of the breast are well circumscribed and are composed of benign epithelium with sparse stroma, which is the histologic feature that differentiates them from fibroadenomas. They may be divided into tubular adenomas and lactating adenomas. Tubular adenomas are seen in young nonpregnant women, whereas lactating adenomas are seen during pregnancy or during the postpartum period. Ham-artomas are discrete breast tumors that are usually 2 to 4 cm in diameter, firm, and
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young nonpregnant women, whereas lactating adenomas are seen during pregnancy or during the postpartum period. Ham-artomas are discrete breast tumors that are usually 2 to 4 cm in diameter, firm, and sharply circumscribed. Adenolipomas con-sist of sharply circumscribed nodules of fatty tissue that contain normal breast lobules and ducts.Fibrocystic Disease. The term fibrocystic disease is nonspe-cific. Too frequently, it is used as a diagnostic term to describe symptoms, to rationalize the need for breast biopsy, and to explain biopsy results. Synonyms include fibrocystic changes, cystic mastopathy, chronic cystic disease, chronic cystic mas-titis, Schimmelbusch’s disease, mazoplasia, Cooper’s disease, Reclus’ disease, and fibroadenomatosis. Fibrocystic disease refers to a spectrum of histopathologic changes that are best diagnosed and treated specifically.Pathology of Proliferative Disorders Without AtypiaProliferative breast disorders without atypia include sclerosing adenosis,
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Surgery_Schwartz. young nonpregnant women, whereas lactating adenomas are seen during pregnancy or during the postpartum period. Ham-artomas are discrete breast tumors that are usually 2 to 4 cm in diameter, firm, and sharply circumscribed. Adenolipomas con-sist of sharply circumscribed nodules of fatty tissue that contain normal breast lobules and ducts.Fibrocystic Disease. The term fibrocystic disease is nonspe-cific. Too frequently, it is used as a diagnostic term to describe symptoms, to rationalize the need for breast biopsy, and to explain biopsy results. Synonyms include fibrocystic changes, cystic mastopathy, chronic cystic disease, chronic cystic mas-titis, Schimmelbusch’s disease, mazoplasia, Cooper’s disease, Reclus’ disease, and fibroadenomatosis. Fibrocystic disease refers to a spectrum of histopathologic changes that are best diagnosed and treated specifically.Pathology of Proliferative Disorders Without AtypiaProliferative breast disorders without atypia include sclerosing adenosis,
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histopathologic changes that are best diagnosed and treated specifically.Pathology of Proliferative Disorders Without AtypiaProliferative breast disorders without atypia include sclerosing adenosis, radial scars, complex sclerosing lesions, ductal epithe-lial hyperplasia, and intraductal papillomas.32,33 Sclerosing ade-nosis is prevalent during the childbearing and perimenopausal years and has no malignant potential. Histologic changes are both proliferative (ductal proliferation) and involutional (stro-mal fibrosis, epithelial regression). Sclerosing adenosis is char-acterized by distorted breast lobules and usually occurs in the context of multiple microcysts, but occasionally presents as a palpable mass. Benign calcifications are often associated with this disorder. Sclerosing adenosis can be managed by observa-tion as long as the imaging features and pathologic findings are concordant. Central sclerosis and various degrees of epithelial proliferation, apocrine metaplasia, and
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Surgery_Schwartz. histopathologic changes that are best diagnosed and treated specifically.Pathology of Proliferative Disorders Without AtypiaProliferative breast disorders without atypia include sclerosing adenosis, radial scars, complex sclerosing lesions, ductal epithe-lial hyperplasia, and intraductal papillomas.32,33 Sclerosing ade-nosis is prevalent during the childbearing and perimenopausal years and has no malignant potential. Histologic changes are both proliferative (ductal proliferation) and involutional (stro-mal fibrosis, epithelial regression). Sclerosing adenosis is char-acterized by distorted breast lobules and usually occurs in the context of multiple microcysts, but occasionally presents as a palpable mass. Benign calcifications are often associated with this disorder. Sclerosing adenosis can be managed by observa-tion as long as the imaging features and pathologic findings are concordant. Central sclerosis and various degrees of epithelial proliferation, apocrine metaplasia, and
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can be managed by observa-tion as long as the imaging features and pathologic findings are concordant. Central sclerosis and various degrees of epithelial proliferation, apocrine metaplasia, and papilloma formation characterize radial scars and complex sclerosing lesions of the breast. Lesions up to 1 cm in diameter are called radial scars, whereas larger lesions are called complex sclerosing lesions. Radial scars originate at sites of terminal duct branching where the characteristic histologic changes radiate from a central area of fibrosis. All of the histologic features of a radial scar are seen in the larger complex sclerosing lesions, but there is a greater disturbance of structure with papilloma formation, apocrine metaplasia, and occasionally sclerosing adenosis. Distinguish-ing between a radial scar and invasive breast carcinoma can be challenging based on core-needle biopsy sampling. Often the imaging features of a radial scar (which can be quite similar to an invasive
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Surgery_Schwartz. can be managed by observa-tion as long as the imaging features and pathologic findings are concordant. Central sclerosis and various degrees of epithelial proliferation, apocrine metaplasia, and papilloma formation characterize radial scars and complex sclerosing lesions of the breast. Lesions up to 1 cm in diameter are called radial scars, whereas larger lesions are called complex sclerosing lesions. Radial scars originate at sites of terminal duct branching where the characteristic histologic changes radiate from a central area of fibrosis. All of the histologic features of a radial scar are seen in the larger complex sclerosing lesions, but there is a greater disturbance of structure with papilloma formation, apocrine metaplasia, and occasionally sclerosing adenosis. Distinguish-ing between a radial scar and invasive breast carcinoma can be challenging based on core-needle biopsy sampling. Often the imaging features of a radial scar (which can be quite similar to an invasive
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Surgery_Schwartz_3753
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Surgery_Schwartz
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between a radial scar and invasive breast carcinoma can be challenging based on core-needle biopsy sampling. Often the imaging features of a radial scar (which can be quite similar to an invasive cancer) will dictate the need for either a vacuum-assisted biopsy or surgical excision in order to exclude the pos-sibility of carcinoma.Mild ductal hyperplasia is characterized by the presence of three or four cell layers above the basement membrane. Moder-ate ductal hyperplasia is characterized by the presence of five or more cell layers above the basement membrane. Florid duc-tal epithelial hyperplasia occupies at least 70% of a minor duct lumen. It is found in >20% of breast tissue specimens, is either solid or papillary, and is associated with an increased cancer risk (see Table 17-3). Intraductal papillomas arise in the major ducts, usually in premenopausal women. They generally are <0.5 cm in diameter but may be as large as 5 cm. A common presenting symptom is nipple discharge, which
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Surgery_Schwartz. between a radial scar and invasive breast carcinoma can be challenging based on core-needle biopsy sampling. Often the imaging features of a radial scar (which can be quite similar to an invasive cancer) will dictate the need for either a vacuum-assisted biopsy or surgical excision in order to exclude the pos-sibility of carcinoma.Mild ductal hyperplasia is characterized by the presence of three or four cell layers above the basement membrane. Moder-ate ductal hyperplasia is characterized by the presence of five or more cell layers above the basement membrane. Florid duc-tal epithelial hyperplasia occupies at least 70% of a minor duct lumen. It is found in >20% of breast tissue specimens, is either solid or papillary, and is associated with an increased cancer risk (see Table 17-3). Intraductal papillomas arise in the major ducts, usually in premenopausal women. They generally are <0.5 cm in diameter but may be as large as 5 cm. A common presenting symptom is nipple discharge, which
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Surgery_Schwartz_3754
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papillomas arise in the major ducts, usually in premenopausal women. They generally are <0.5 cm in diameter but may be as large as 5 cm. A common presenting symptom is nipple discharge, which may be serous or bloody. Grossly, intraductal papillomas are pinkish tan, fri-able, and usually attached to the wall of the involved duct by a stalk. They rarely undergo malignant transformation, and their presence does not increase a woman’s risk of developing breast cancer (unless accompanied by atypia). However, multiple intraductal papillomas, which occur in younger women and are less frequently associated with nipple discharge, are susceptible to malignant transformation.Pathology of Atypical Proliferative DiseasesThe atypical proliferative diseases have some of the features of carcinoma in situ but either lack a major defining feature of car-cinoma in situ or have the features in less than fully developed form.34 Atypical ductal hyperplasia (ADH) appears similar to low grade ductal
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Surgery_Schwartz. papillomas arise in the major ducts, usually in premenopausal women. They generally are <0.5 cm in diameter but may be as large as 5 cm. A common presenting symptom is nipple discharge, which may be serous or bloody. Grossly, intraductal papillomas are pinkish tan, fri-able, and usually attached to the wall of the involved duct by a stalk. They rarely undergo malignant transformation, and their presence does not increase a woman’s risk of developing breast cancer (unless accompanied by atypia). However, multiple intraductal papillomas, which occur in younger women and are less frequently associated with nipple discharge, are susceptible to malignant transformation.Pathology of Atypical Proliferative DiseasesThe atypical proliferative diseases have some of the features of carcinoma in situ but either lack a major defining feature of car-cinoma in situ or have the features in less than fully developed form.34 Atypical ductal hyperplasia (ADH) appears similar to low grade ductal
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Surgery_Schwartz_3755
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in situ but either lack a major defining feature of car-cinoma in situ or have the features in less than fully developed form.34 Atypical ductal hyperplasia (ADH) appears similar to low grade ductal carcinoma in situ (DCIS) histologically and is composed of monotonous round, cuboidal, or polygonal cells enclosed by basement membrane with rare mitoses. A lesion will be considered to be ADH if it is up to 2 or 3 mm in size but would be called DCIS if it is larger than 3 mm. The diagnosis can be difficult to establish with core-needle biopsy specimen alone and many cases will require excisional biopsy specimen for classification. Individuals with a diagnosis of ADH are at increased risk for development of breast cancer and should be counseled appropriately regarding risk reduction strategies.In 1978, Haagensen et al described lobular neoplasia, a spectrum of disorders ranging from atypical lobular hyperplasia to lobular carcinoma in situ (LCIS).35 Atypical lobular hyper-plasia (ALH)
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Surgery_Schwartz. in situ but either lack a major defining feature of car-cinoma in situ or have the features in less than fully developed form.34 Atypical ductal hyperplasia (ADH) appears similar to low grade ductal carcinoma in situ (DCIS) histologically and is composed of monotonous round, cuboidal, or polygonal cells enclosed by basement membrane with rare mitoses. A lesion will be considered to be ADH if it is up to 2 or 3 mm in size but would be called DCIS if it is larger than 3 mm. The diagnosis can be difficult to establish with core-needle biopsy specimen alone and many cases will require excisional biopsy specimen for classification. Individuals with a diagnosis of ADH are at increased risk for development of breast cancer and should be counseled appropriately regarding risk reduction strategies.In 1978, Haagensen et al described lobular neoplasia, a spectrum of disorders ranging from atypical lobular hyperplasia to lobular carcinoma in situ (LCIS).35 Atypical lobular hyper-plasia (ALH)
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Surgery_Schwartz_3756
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1978, Haagensen et al described lobular neoplasia, a spectrum of disorders ranging from atypical lobular hyperplasia to lobular carcinoma in situ (LCIS).35 Atypical lobular hyper-plasia (ALH) results in minimal distention of lobular units with cells that are similar to those seen in LCIS. The diagnosis of LCIS is made when small monomorphic cells that distend the terminal ductal lobular unit are noted. In cases of LCIS, the acini are full and distended while the overall lobular architec-ture is maintained (Fig. 17-12). Classic LCIS is not associated with a specific mammographic or palpable abnormality but is Brunicardi_Ch17_p0541-p0612.indd 55301/03/19 5:04 PM 554SPECIFIC CONSIDERATIONSPART IIFigure 17-12. Lobular carcinoma in situ (100x). There are small monomorphic cells that distend the terminal duct lobular unit, with-out necrosis or mitoses. (Used with permission from Dr. Sindhu Menon, Consultant Histopathologist and Dr. Rahul Deb, Consul-tant Histopathologist and Lead Breast
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Surgery_Schwartz. 1978, Haagensen et al described lobular neoplasia, a spectrum of disorders ranging from atypical lobular hyperplasia to lobular carcinoma in situ (LCIS).35 Atypical lobular hyper-plasia (ALH) results in minimal distention of lobular units with cells that are similar to those seen in LCIS. The diagnosis of LCIS is made when small monomorphic cells that distend the terminal ductal lobular unit are noted. In cases of LCIS, the acini are full and distended while the overall lobular architec-ture is maintained (Fig. 17-12). Classic LCIS is not associated with a specific mammographic or palpable abnormality but is Brunicardi_Ch17_p0541-p0612.indd 55301/03/19 5:04 PM 554SPECIFIC CONSIDERATIONSPART IIFigure 17-12. Lobular carcinoma in situ (100x). There are small monomorphic cells that distend the terminal duct lobular unit, with-out necrosis or mitoses. (Used with permission from Dr. Sindhu Menon, Consultant Histopathologist and Dr. Rahul Deb, Consul-tant Histopathologist and Lead Breast
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Surgery_Schwartz_3757
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the terminal duct lobular unit, with-out necrosis or mitoses. (Used with permission from Dr. Sindhu Menon, Consultant Histopathologist and Dr. Rahul Deb, Consul-tant Histopathologist and Lead Breast Pathologist, Royal Derby Hospital, Derby, UK.)an incidental finding noted on breast biopsy. There is a variant of LCIS that has been termed pleomorphic LCIS. In the case of pleomorphic LCIS, there can be calcifications or other suspi-cious mammographic changes that dictate the need for biopsy. Classic LCIS is not treated with excision as the patient is at risk for developing invasive breast cancer in either breast and therefore the patient is counseled regarding appropriate risk reduction strategies. Pleomorphic LCIS can be difficult to dis-tinguish from high-grade DCIS and there are some proponents who have suggested that patients with pleomorphic LCIS be managed similar to those with DCIS with attention to margins and consideration for radiation therapy in the setting of breast
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Surgery_Schwartz. the terminal duct lobular unit, with-out necrosis or mitoses. (Used with permission from Dr. Sindhu Menon, Consultant Histopathologist and Dr. Rahul Deb, Consul-tant Histopathologist and Lead Breast Pathologist, Royal Derby Hospital, Derby, UK.)an incidental finding noted on breast biopsy. There is a variant of LCIS that has been termed pleomorphic LCIS. In the case of pleomorphic LCIS, there can be calcifications or other suspi-cious mammographic changes that dictate the need for biopsy. Classic LCIS is not treated with excision as the patient is at risk for developing invasive breast cancer in either breast and therefore the patient is counseled regarding appropriate risk reduction strategies. Pleomorphic LCIS can be difficult to dis-tinguish from high-grade DCIS and there are some proponents who have suggested that patients with pleomorphic LCIS be managed similar to those with DCIS with attention to margins and consideration for radiation therapy in the setting of breast
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Surgery_Schwartz_3758
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Surgery_Schwartz
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some proponents who have suggested that patients with pleomorphic LCIS be managed similar to those with DCIS with attention to margins and consideration for radiation therapy in the setting of breast conserving treatment. The use of immunohistochemical stain-ing for E-cadherin can help to discriminate between LCIS and DCIS. In lobular neoplasias, such as ALH and LCIS, there is a lack of E-cadherin expression, whereas the majority of ductal lesions will demonstrate E-cadherin reactivity.Treatment of Selected Benign Breast Disorders and DiseasesCysts. Because needle biopsy of breast masses may produce artifacts that make mammography assessment more difficult, many multidisciplinary teams prefer to image breast masses before performing either fine-needle aspiration or core-needle biopsy.36,37 In practice, however, the first investigation of pal-pable breast masses may be a needle biopsy, which allows for the early diagnosis of cysts. A 21-gauge needle attached to a 10-mL syringe is
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Surgery_Schwartz. some proponents who have suggested that patients with pleomorphic LCIS be managed similar to those with DCIS with attention to margins and consideration for radiation therapy in the setting of breast conserving treatment. The use of immunohistochemical stain-ing for E-cadherin can help to discriminate between LCIS and DCIS. In lobular neoplasias, such as ALH and LCIS, there is a lack of E-cadherin expression, whereas the majority of ductal lesions will demonstrate E-cadherin reactivity.Treatment of Selected Benign Breast Disorders and DiseasesCysts. Because needle biopsy of breast masses may produce artifacts that make mammography assessment more difficult, many multidisciplinary teams prefer to image breast masses before performing either fine-needle aspiration or core-needle biopsy.36,37 In practice, however, the first investigation of pal-pable breast masses may be a needle biopsy, which allows for the early diagnosis of cysts. A 21-gauge needle attached to a 10-mL syringe is
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Surgery_Schwartz_3759
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Surgery_Schwartz
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In practice, however, the first investigation of pal-pable breast masses may be a needle biopsy, which allows for the early diagnosis of cysts. A 21-gauge needle attached to a 10-mL syringe is placed directly into the mass, which is fixed by fingers of the nondominant hand. The volume of a typical cyst is 5 to 10 mL, but it may be 75 mL or more. If the fluid that is aspirated is not bloodstained, then the cyst is aspirated to dryness, the needle is removed, and the fluid is discarded because cytologic examination of such fluid is not cost effec-tive. After aspiration, the breast is carefully palpated to exclude a residual mass. In most cases, however, imaging has been per-formed prior to a needle being introduced into the breast, and indeed the majority of cysts are now aspirated under ultrasound guidance. If a mass was noted on initial ultrasound or there is a residual mass post aspiration, then a tissue specimen is obtained, usually by core biopsy. When cystic fluid is bloodstained,
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Surgery_Schwartz. In practice, however, the first investigation of pal-pable breast masses may be a needle biopsy, which allows for the early diagnosis of cysts. A 21-gauge needle attached to a 10-mL syringe is placed directly into the mass, which is fixed by fingers of the nondominant hand. The volume of a typical cyst is 5 to 10 mL, but it may be 75 mL or more. If the fluid that is aspirated is not bloodstained, then the cyst is aspirated to dryness, the needle is removed, and the fluid is discarded because cytologic examination of such fluid is not cost effec-tive. After aspiration, the breast is carefully palpated to exclude a residual mass. In most cases, however, imaging has been per-formed prior to a needle being introduced into the breast, and indeed the majority of cysts are now aspirated under ultrasound guidance. If a mass was noted on initial ultrasound or there is a residual mass post aspiration, then a tissue specimen is obtained, usually by core biopsy. When cystic fluid is bloodstained,
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Surgery_Schwartz_3760
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Surgery_Schwartz
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guidance. If a mass was noted on initial ultrasound or there is a residual mass post aspiration, then a tissue specimen is obtained, usually by core biopsy. When cystic fluid is bloodstained, fluid can be sent for cytologic examination. A simple cyst is rarely of concern, but a complex cyst may be the result of an underlying malignancy. A pneumocystogram can be obtained by injecting air into the cyst and then obtaining a repeat mammogram. When this technique is used, the wall of the cyst cavity can be more carefully assessed for any irregularities.Fibroadenomas. Most fibroadenomas are self-limiting and many go undiagnosed, so a more conservative approach is reasonable. Careful ultrasound examination with core-needle biopsy will provide for an accurate diagnosis. Ultrasonogra-phy may reveal specific features that are pathognomonic for fibroadenoma, and in a young woman (e.g., under 25 years) where the risk of breast cancer is already very low a core-needle biopsy may not be necessary.
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Surgery_Schwartz. guidance. If a mass was noted on initial ultrasound or there is a residual mass post aspiration, then a tissue specimen is obtained, usually by core biopsy. When cystic fluid is bloodstained, fluid can be sent for cytologic examination. A simple cyst is rarely of concern, but a complex cyst may be the result of an underlying malignancy. A pneumocystogram can be obtained by injecting air into the cyst and then obtaining a repeat mammogram. When this technique is used, the wall of the cyst cavity can be more carefully assessed for any irregularities.Fibroadenomas. Most fibroadenomas are self-limiting and many go undiagnosed, so a more conservative approach is reasonable. Careful ultrasound examination with core-needle biopsy will provide for an accurate diagnosis. Ultrasonogra-phy may reveal specific features that are pathognomonic for fibroadenoma, and in a young woman (e.g., under 25 years) where the risk of breast cancer is already very low a core-needle biopsy may not be necessary.
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Surgery_Schwartz_3761
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specific features that are pathognomonic for fibroadenoma, and in a young woman (e.g., under 25 years) where the risk of breast cancer is already very low a core-needle biopsy may not be necessary. In patients where biopsy is performed, the patient is counseled concerning the ultra-sound and biopsy results, and surgical excision of the fibroad-enoma may be avoided. Cryoablation and ultrasound-guided vacuum-assisted biopsy are approved treatments for fibroad-enomas of the breast, especially lesions <3 cm. Larger lesions are often still best treated by excision. With short-term follow-up, a significant percentage of fibroadenomas will decrease in size and will no longer be palpable.38 However, many will remain palpable, especially those larger than 2 cm.39 There-fore, women should be counseled that the options for treat-ment include surgical removal, cryoablation, vacuum assisted biopsy, or observation.Sclerosing Disorders. The clinical significance of scleros-ing adenosis lies in its
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Surgery_Schwartz. specific features that are pathognomonic for fibroadenoma, and in a young woman (e.g., under 25 years) where the risk of breast cancer is already very low a core-needle biopsy may not be necessary. In patients where biopsy is performed, the patient is counseled concerning the ultra-sound and biopsy results, and surgical excision of the fibroad-enoma may be avoided. Cryoablation and ultrasound-guided vacuum-assisted biopsy are approved treatments for fibroad-enomas of the breast, especially lesions <3 cm. Larger lesions are often still best treated by excision. With short-term follow-up, a significant percentage of fibroadenomas will decrease in size and will no longer be palpable.38 However, many will remain palpable, especially those larger than 2 cm.39 There-fore, women should be counseled that the options for treat-ment include surgical removal, cryoablation, vacuum assisted biopsy, or observation.Sclerosing Disorders. The clinical significance of scleros-ing adenosis lies in its
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Surgery_Schwartz_3762
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Surgery_Schwartz
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that the options for treat-ment include surgical removal, cryoablation, vacuum assisted biopsy, or observation.Sclerosing Disorders. The clinical significance of scleros-ing adenosis lies in its imitation of cancer. On physical exami-nation, it may be confused with cancer, by mammography, and at gross pathologic examination. Excisional biopsy and histologic examination are frequently necessary to exclude the diagnosis of cancer. The diagnostic work-up for radial scars and complex sclerosing lesions frequently involves stereo-tactic biopsy. It usually is not possible to differentiate these lesions with certainty from cancer by mammographic features, so a larger tissue biopsy is recommended either by way of vacuum-assisted biopsy or an open surgical excisional biopsy. The mammographic appearance of a radial scar or sclerosing adenosis (mass density with spiculated margins) will usually lead to an assessment that the results of a core-needle biopsy specimen showing benign disease are
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Surgery_Schwartz. that the options for treat-ment include surgical removal, cryoablation, vacuum assisted biopsy, or observation.Sclerosing Disorders. The clinical significance of scleros-ing adenosis lies in its imitation of cancer. On physical exami-nation, it may be confused with cancer, by mammography, and at gross pathologic examination. Excisional biopsy and histologic examination are frequently necessary to exclude the diagnosis of cancer. The diagnostic work-up for radial scars and complex sclerosing lesions frequently involves stereo-tactic biopsy. It usually is not possible to differentiate these lesions with certainty from cancer by mammographic features, so a larger tissue biopsy is recommended either by way of vacuum-assisted biopsy or an open surgical excisional biopsy. The mammographic appearance of a radial scar or sclerosing adenosis (mass density with spiculated margins) will usually lead to an assessment that the results of a core-needle biopsy specimen showing benign disease are
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Surgery_Schwartz_3763
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Surgery_Schwartz
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of a radial scar or sclerosing adenosis (mass density with spiculated margins) will usually lead to an assessment that the results of a core-needle biopsy specimen showing benign disease are discordant with the radiographic findings.Periductal Mastitis. Painful and tender masses behind the nipple-areola complex are aspirated with a 21-gauge needle attached to a 10-mL syringe. Any fluid obtained is submitted for culture using a transport medium appropriate for the detec-tion of anaerobic organisms. In the absence of pus, women are started on a combination of antibiotics to cover polymicrobial infections while awaiting the results of culture. Antibiotics are then continued based on sensitivity tests. Many cases respond satisfactorily to antibiotics alone, but when considerable puru-lent material is present, repeated ultrasound guided aspiration is performed, and ultimately in a proportion of cases surgical treatment is required. Unlike puerperal abscesses, a subareo-lar abscess is
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Surgery_Schwartz. of a radial scar or sclerosing adenosis (mass density with spiculated margins) will usually lead to an assessment that the results of a core-needle biopsy specimen showing benign disease are discordant with the radiographic findings.Periductal Mastitis. Painful and tender masses behind the nipple-areola complex are aspirated with a 21-gauge needle attached to a 10-mL syringe. Any fluid obtained is submitted for culture using a transport medium appropriate for the detec-tion of anaerobic organisms. In the absence of pus, women are started on a combination of antibiotics to cover polymicrobial infections while awaiting the results of culture. Antibiotics are then continued based on sensitivity tests. Many cases respond satisfactorily to antibiotics alone, but when considerable puru-lent material is present, repeated ultrasound guided aspiration is performed, and ultimately in a proportion of cases surgical treatment is required. Unlike puerperal abscesses, a subareo-lar abscess is
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Surgery_Schwartz_3764
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material is present, repeated ultrasound guided aspiration is performed, and ultimately in a proportion of cases surgical treatment is required. Unlike puerperal abscesses, a subareo-lar abscess is usually unilocular and often is associated with a single duct system. Ultrasound will accurately delineate its extent. In those cases that come to surgery, the surgeon may either undertake simple drainage with a view toward formal Brunicardi_Ch17_p0541-p0612.indd 55401/03/19 5:04 PM 555THE BREASTCHAPTER 17Table 17-5Treatment of recurrent subareolar sepsisSUITABLE FOR FISTULECTOMYSUITABLE FOR TOTAL DUCT EXCISIONSmall abscess localized to one segmentLarge abscess affecting >50% of the areolar circumferenceRecurrence involving the same segmentRecurrence involving a different segmentMild or no nipple inversionMarked nipple inversionPatient unconcerned about nipple inversionPatient requests correction of nipple inversionYounger patientOlder patientNo discharge from other ductsPurulent
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Surgery_Schwartz. material is present, repeated ultrasound guided aspiration is performed, and ultimately in a proportion of cases surgical treatment is required. Unlike puerperal abscesses, a subareo-lar abscess is usually unilocular and often is associated with a single duct system. Ultrasound will accurately delineate its extent. In those cases that come to surgery, the surgeon may either undertake simple drainage with a view toward formal Brunicardi_Ch17_p0541-p0612.indd 55401/03/19 5:04 PM 555THE BREASTCHAPTER 17Table 17-5Treatment of recurrent subareolar sepsisSUITABLE FOR FISTULECTOMYSUITABLE FOR TOTAL DUCT EXCISIONSmall abscess localized to one segmentLarge abscess affecting >50% of the areolar circumferenceRecurrence involving the same segmentRecurrence involving a different segmentMild or no nipple inversionMarked nipple inversionPatient unconcerned about nipple inversionPatient requests correction of nipple inversionYounger patientOlder patientNo discharge from other ductsPurulent
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Surgery_Schwartz_3765
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or no nipple inversionMarked nipple inversionPatient unconcerned about nipple inversionPatient requests correction of nipple inversionYounger patientOlder patientNo discharge from other ductsPurulent discharge from other ductsNo prior fistulectomyRecurrence after fistulectomyModified with permission from Mansel RE, Webster DJT: Benign Disorders and Diseases of the Breast: Concepts and Clinical Management, 2nd ed. London: Elsevier/Saunders; 2000.surgery, should the problem recur, or proceed with definitive surgery. In a woman of childbearing age, simple drainage is preferred, but if there is an anaerobic infection, recurrent infection frequently develops. Recurrent abscess with fistula is a difficult problem. Treatment of periductal fistula was ini-tially recommended to be opening up of the fistulous track and allowing it to granulate.40 This approach may still be used, especially if the fistula is recurrent after previous attempts at fistulectomy. However, nowadays the preferred
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Surgery_Schwartz. or no nipple inversionMarked nipple inversionPatient unconcerned about nipple inversionPatient requests correction of nipple inversionYounger patientOlder patientNo discharge from other ductsPurulent discharge from other ductsNo prior fistulectomyRecurrence after fistulectomyModified with permission from Mansel RE, Webster DJT: Benign Disorders and Diseases of the Breast: Concepts and Clinical Management, 2nd ed. London: Elsevier/Saunders; 2000.surgery, should the problem recur, or proceed with definitive surgery. In a woman of childbearing age, simple drainage is preferred, but if there is an anaerobic infection, recurrent infection frequently develops. Recurrent abscess with fistula is a difficult problem. Treatment of periductal fistula was ini-tially recommended to be opening up of the fistulous track and allowing it to granulate.40 This approach may still be used, especially if the fistula is recurrent after previous attempts at fistulectomy. However, nowadays the preferred
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Surgery_Schwartz_3766
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Surgery_Schwartz
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of the fistulous track and allowing it to granulate.40 This approach may still be used, especially if the fistula is recurrent after previous attempts at fistulectomy. However, nowadays the preferred initial surgical treatment is by fistulectomy and primary closure with anti-biotic coverage.41 Excision of all the major ducts is an alter-native option depending on the circumstances (Table 17-5). When a localized periareolar abscess recurs at the previous site and a fistula is present, the preferred operation is fistulec-tomy, which has minimal complications and a high degree of success. However, when subareolar sepsis is diffused rather than localized to one segment or when more than one fistula is present, total duct excision is the most expeditious approach. The first circumstance is seen in young women with squamous metaplasia of a single duct, whereas the latter circumstance is seen in older women with multiple ectatic ducts. Age is not always a reliable guide, however, and fistula
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Surgery_Schwartz. of the fistulous track and allowing it to granulate.40 This approach may still be used, especially if the fistula is recurrent after previous attempts at fistulectomy. However, nowadays the preferred initial surgical treatment is by fistulectomy and primary closure with anti-biotic coverage.41 Excision of all the major ducts is an alter-native option depending on the circumstances (Table 17-5). When a localized periareolar abscess recurs at the previous site and a fistula is present, the preferred operation is fistulec-tomy, which has minimal complications and a high degree of success. However, when subareolar sepsis is diffused rather than localized to one segment or when more than one fistula is present, total duct excision is the most expeditious approach. The first circumstance is seen in young women with squamous metaplasia of a single duct, whereas the latter circumstance is seen in older women with multiple ectatic ducts. Age is not always a reliable guide, however, and fistula
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Surgery_Schwartz_3767
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in young women with squamous metaplasia of a single duct, whereas the latter circumstance is seen in older women with multiple ectatic ducts. Age is not always a reliable guide, however, and fistula excision is the preferred initial procedure for localized sepsis irrespective of age. Antibiotic therapy is useful for recurrent infection after fistula excision, and a 2to 4-week course is recommended before total duct excision.Nipple Inversion. More women request correction of con-genital nipple inversion than request correction for the nipple inversion that occurs secondary to duct ectasia. Although the results are usually satisfactory, women seeking correction for cosmetic reasons should always be made aware of the surgi-cal complications of altered nipple sensation, nipple necrosis, and postoperative fibrosis with nipple retraction. Because nipple inversion is a result of shortening of the subareolar ducts, a com-plete division of these ducts is necessary for permanent correc-tion of
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Surgery_Schwartz. in young women with squamous metaplasia of a single duct, whereas the latter circumstance is seen in older women with multiple ectatic ducts. Age is not always a reliable guide, however, and fistula excision is the preferred initial procedure for localized sepsis irrespective of age. Antibiotic therapy is useful for recurrent infection after fistula excision, and a 2to 4-week course is recommended before total duct excision.Nipple Inversion. More women request correction of con-genital nipple inversion than request correction for the nipple inversion that occurs secondary to duct ectasia. Although the results are usually satisfactory, women seeking correction for cosmetic reasons should always be made aware of the surgi-cal complications of altered nipple sensation, nipple necrosis, and postoperative fibrosis with nipple retraction. Because nipple inversion is a result of shortening of the subareolar ducts, a com-plete division of these ducts is necessary for permanent correc-tion of
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Surgery_Schwartz_3768
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Surgery_Schwartz
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fibrosis with nipple retraction. Because nipple inversion is a result of shortening of the subareolar ducts, a com-plete division of these ducts is necessary for permanent correc-tion of the disorder.RISK FACTORS FOR BREAST CANCERHormonal and Nonhormonal Risk FactorsIncreased exposure to estrogen is associated with an increased risk for developing breast cancer, whereas reducing exposure is thought to be protective.42-48 Correspondingly, factors that increase the number of menstrual cycles, such as early men-arche, nulliparity, and late menopause, are associated with increased risk. Moderate levels of exercise and a longer lacta-tion period, factors that decrease the total number of menstrual cycles, are protective. The terminal differentiation of breast epi-thelium associated with a full-term pregnancy is also protective, so older age at first live birth is associated with an increased risk of breast cancer. Finally, there is an association between obesity and increased breast cancer
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Surgery_Schwartz. fibrosis with nipple retraction. Because nipple inversion is a result of shortening of the subareolar ducts, a com-plete division of these ducts is necessary for permanent correc-tion of the disorder.RISK FACTORS FOR BREAST CANCERHormonal and Nonhormonal Risk FactorsIncreased exposure to estrogen is associated with an increased risk for developing breast cancer, whereas reducing exposure is thought to be protective.42-48 Correspondingly, factors that increase the number of menstrual cycles, such as early men-arche, nulliparity, and late menopause, are associated with increased risk. Moderate levels of exercise and a longer lacta-tion period, factors that decrease the total number of menstrual cycles, are protective. The terminal differentiation of breast epi-thelium associated with a full-term pregnancy is also protective, so older age at first live birth is associated with an increased risk of breast cancer. Finally, there is an association between obesity and increased breast cancer
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Surgery_Schwartz_3769
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Surgery_Schwartz
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pregnancy is also protective, so older age at first live birth is associated with an increased risk of breast cancer. Finally, there is an association between obesity and increased breast cancer risk. Because the major source of estrogen in postmenopausal women is the conversion of andro-stenedione to estrone by adipose tissue, obesity is associated with a long-term increase in estrogen exposure.Nonhormonal risk factors include radiation exposure. Young women who receive mantle radiation therapy for Hodg-kin’s lymphoma have a breast cancer risk that is 75 times greater than that of age-matched control subjects. Survivors of the atomic bomb blasts in Japan during World War II have a very high incidence of breast cancer, likely because of somatic muta-tions induced by the radiation exposure. In both circumstances, radiation exposure during adolescence, a period of active breast development, magnifies the deleterious effect. Studies also sug-gest that the risk of breast cancer increases
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Surgery_Schwartz. pregnancy is also protective, so older age at first live birth is associated with an increased risk of breast cancer. Finally, there is an association between obesity and increased breast cancer risk. Because the major source of estrogen in postmenopausal women is the conversion of andro-stenedione to estrone by adipose tissue, obesity is associated with a long-term increase in estrogen exposure.Nonhormonal risk factors include radiation exposure. Young women who receive mantle radiation therapy for Hodg-kin’s lymphoma have a breast cancer risk that is 75 times greater than that of age-matched control subjects. Survivors of the atomic bomb blasts in Japan during World War II have a very high incidence of breast cancer, likely because of somatic muta-tions induced by the radiation exposure. In both circumstances, radiation exposure during adolescence, a period of active breast development, magnifies the deleterious effect. Studies also sug-gest that the risk of breast cancer increases
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In both circumstances, radiation exposure during adolescence, a period of active breast development, magnifies the deleterious effect. Studies also sug-gest that the risk of breast cancer increases as the amount of alcohol a woman consumes increases.49 Alcohol consumption is known to increase serum levels of estradiol. Finally, evidence suggests that long-term consumption of foods with a high fat content contributes to an increased risk of breast cancer by increasing serum estrogen levels.Risk Assessment ModelsThe average lifetime risk of breast cancer for newborn U.S. women is 12%.50,51 The longer a woman lives without cancer, the lower her risk of developing breast cancer. Thus, a woman age 50 years has an 11% lifetime risk of developing breast cancer, and a woman age 70 years has a 7% lifetime risk of developing breast cancer. Because risk factors for breast cancer interact, evaluating the risk conferred by combinations of risk factors is difficult. There are several risk
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Surgery_Schwartz. In both circumstances, radiation exposure during adolescence, a period of active breast development, magnifies the deleterious effect. Studies also sug-gest that the risk of breast cancer increases as the amount of alcohol a woman consumes increases.49 Alcohol consumption is known to increase serum levels of estradiol. Finally, evidence suggests that long-term consumption of foods with a high fat content contributes to an increased risk of breast cancer by increasing serum estrogen levels.Risk Assessment ModelsThe average lifetime risk of breast cancer for newborn U.S. women is 12%.50,51 The longer a woman lives without cancer, the lower her risk of developing breast cancer. Thus, a woman age 50 years has an 11% lifetime risk of developing breast cancer, and a woman age 70 years has a 7% lifetime risk of developing breast cancer. Because risk factors for breast cancer interact, evaluating the risk conferred by combinations of risk factors is difficult. There are several risk
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has a 7% lifetime risk of developing breast cancer. Because risk factors for breast cancer interact, evaluating the risk conferred by combinations of risk factors is difficult. There are several risk assessment models available to predict the risk of breast cancer. From the Breast Cancer Detec-tion Demonstration Project, a mammography screening program conducted in the 1970s, Gail et al developed the model most frequently used in the United States, which incorporates age, age at menarche, age at first live birth, the number of breast biopsy specimens, any history of atypical hyperplasia, and number of first-degree relatives with breast cancer.52 It predicts the cumula-tive risk of breast cancer according to decade of life. To calculate breast cancer risk using the Gail model, a woman’s risk factors are translated into an overall risk score by multiplying her rela-tive risks from several categories (Table 17-6). This risk score is then compared to an adjusted population risk of breast
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Surgery_Schwartz. has a 7% lifetime risk of developing breast cancer. Because risk factors for breast cancer interact, evaluating the risk conferred by combinations of risk factors is difficult. There are several risk assessment models available to predict the risk of breast cancer. From the Breast Cancer Detec-tion Demonstration Project, a mammography screening program conducted in the 1970s, Gail et al developed the model most frequently used in the United States, which incorporates age, age at menarche, age at first live birth, the number of breast biopsy specimens, any history of atypical hyperplasia, and number of first-degree relatives with breast cancer.52 It predicts the cumula-tive risk of breast cancer according to decade of life. To calculate breast cancer risk using the Gail model, a woman’s risk factors are translated into an overall risk score by multiplying her rela-tive risks from several categories (Table 17-6). This risk score is then compared to an adjusted population risk of breast
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factors are translated into an overall risk score by multiplying her rela-tive risks from several categories (Table 17-6). This risk score is then compared to an adjusted population risk of breast cancer to determine a woman’s individual or absolute risk. The output is a 5-year risk and a lifetime risk of developing breast cancer. A software program incorporating the Gail model is available from the National Cancer Institute at http://bcra.nci.nih.gov/brc. This model was recently modified to more accu-rately assess risk in African American women.52,53 There have also been modifications that project individualized absolute 5Brunicardi_Ch17_p0541-p0612.indd 55501/03/19 5:04 PM 556SPECIFIC CONSIDERATIONSPART IITable 17-6Relative risk estimates for the Gail modelVARIABLERELATIVE RISKAge at menarche (years) ≥14 12–13 <12Number of biopsy specimens/history of benign breast disease, age <50 y 0 1 ≥2Number of biopsy specimens/history of benign breast disease, age ≥50 y 0 1 ≥2Age at first
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Surgery_Schwartz. factors are translated into an overall risk score by multiplying her rela-tive risks from several categories (Table 17-6). This risk score is then compared to an adjusted population risk of breast cancer to determine a woman’s individual or absolute risk. The output is a 5-year risk and a lifetime risk of developing breast cancer. A software program incorporating the Gail model is available from the National Cancer Institute at http://bcra.nci.nih.gov/brc. This model was recently modified to more accu-rately assess risk in African American women.52,53 There have also been modifications that project individualized absolute 5Brunicardi_Ch17_p0541-p0612.indd 55501/03/19 5:04 PM 556SPECIFIC CONSIDERATIONSPART IITable 17-6Relative risk estimates for the Gail modelVARIABLERELATIVE RISKAge at menarche (years) ≥14 12–13 <12Number of biopsy specimens/history of benign breast disease, age <50 y 0 1 ≥2Number of biopsy specimens/history of benign breast disease, age ≥50 y 0 1 ≥2Age at first
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at menarche (years) ≥14 12–13 <12Number of biopsy specimens/history of benign breast disease, age <50 y 0 1 ≥2Number of biopsy specimens/history of benign breast disease, age ≥50 y 0 1 ≥2Age at first live birth (years) <20 y Number of first-degree relatives with history of breast cancer 0 1 ≥2 20–24 y Number of first-degree relatives with history of breast cancer 0 1 ≥2 25–29 y Number of first-degree relatives with history of breast cancer 0 1 ≥2 ≥30 y Number of first-degree relatives with history of breast cancer 0 1 ≥21.001.101.211.001.702.881.021.271.621.002.616.801.242.685.781.552.764.911.932.834.17Reproduced with permission from Armstrong K, Eisen A, Weber B: Assessing the risk of breast cancer, N Engl J Med. 2000 Feb 24;342(8):564-571.invasive breast cancer risk for Asian and Pacific Island American women. The Gail model is the most widely used model in the United States. Gail and colleagues have also described a revised model that includes body weight and
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Surgery_Schwartz. at menarche (years) ≥14 12–13 <12Number of biopsy specimens/history of benign breast disease, age <50 y 0 1 ≥2Number of biopsy specimens/history of benign breast disease, age ≥50 y 0 1 ≥2Age at first live birth (years) <20 y Number of first-degree relatives with history of breast cancer 0 1 ≥2 20–24 y Number of first-degree relatives with history of breast cancer 0 1 ≥2 25–29 y Number of first-degree relatives with history of breast cancer 0 1 ≥2 ≥30 y Number of first-degree relatives with history of breast cancer 0 1 ≥21.001.101.211.001.702.881.021.271.621.002.616.801.242.685.781.552.764.911.932.834.17Reproduced with permission from Armstrong K, Eisen A, Weber B: Assessing the risk of breast cancer, N Engl J Med. 2000 Feb 24;342(8):564-571.invasive breast cancer risk for Asian and Pacific Island American women. The Gail model is the most widely used model in the United States. Gail and colleagues have also described a revised model that includes body weight and
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for Asian and Pacific Island American women. The Gail model is the most widely used model in the United States. Gail and colleagues have also described a revised model that includes body weight and mammographic density but excludes age at menarche.54Claus et al, using data from the Cancer and Steroid Hor-mone Study, a case-control study of breast cancer, developed the other frequently used risk assessment model, which is based on assumptions about the prevalence of high-penetrance breast cancer susceptibility genes.55 Compared with the Gail model, the Claus model incorporates more information about family his-tory but excludes other risk factors. The Claus model provides individual estimates of breast cancer risk according to decade of life based on presence of firstand second-degree relatives with breast cancer and their age at diagnosis. Risk factors that are less consistently associated with breast cancer (diet, use of oral contraceptives, lactation) or are rare in the general
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Surgery_Schwartz. for Asian and Pacific Island American women. The Gail model is the most widely used model in the United States. Gail and colleagues have also described a revised model that includes body weight and mammographic density but excludes age at menarche.54Claus et al, using data from the Cancer and Steroid Hor-mone Study, a case-control study of breast cancer, developed the other frequently used risk assessment model, which is based on assumptions about the prevalence of high-penetrance breast cancer susceptibility genes.55 Compared with the Gail model, the Claus model incorporates more information about family his-tory but excludes other risk factors. The Claus model provides individual estimates of breast cancer risk according to decade of life based on presence of firstand second-degree relatives with breast cancer and their age at diagnosis. Risk factors that are less consistently associated with breast cancer (diet, use of oral contraceptives, lactation) or are rare in the general
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relatives with breast cancer and their age at diagnosis. Risk factors that are less consistently associated with breast cancer (diet, use of oral contraceptives, lactation) or are rare in the general population (radiation exposure) are not included in either the Gail or Claus risk assessment model. Other models have been proposed that account for mammographic breast density in assessing breast cancer risk.54,56Neither the Gail model nor the Claus model accounts for the risk associated with mutations in the breast cancer suscepti-bility genes BRCA1 and BRCA2 (described in detail in the fol-lowing section). The BRCAPRO model is a Mendelian model that calculates the probability that an individual is a carrier of a mutation in one of the breast cancer susceptibility genes based on their family history of breast and ovarian cancer.57 The prob-ability that an individual will develop breast or ovarian cancer is derived from this mutation probability based on age-specific incidence curves for
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Surgery_Schwartz. relatives with breast cancer and their age at diagnosis. Risk factors that are less consistently associated with breast cancer (diet, use of oral contraceptives, lactation) or are rare in the general population (radiation exposure) are not included in either the Gail or Claus risk assessment model. Other models have been proposed that account for mammographic breast density in assessing breast cancer risk.54,56Neither the Gail model nor the Claus model accounts for the risk associated with mutations in the breast cancer suscepti-bility genes BRCA1 and BRCA2 (described in detail in the fol-lowing section). The BRCAPRO model is a Mendelian model that calculates the probability that an individual is a carrier of a mutation in one of the breast cancer susceptibility genes based on their family history of breast and ovarian cancer.57 The prob-ability that an individual will develop breast or ovarian cancer is derived from this mutation probability based on age-specific incidence curves for
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history of breast and ovarian cancer.57 The prob-ability that an individual will develop breast or ovarian cancer is derived from this mutation probability based on age-specific incidence curves for both mutation carriers and noncarriers.58 Use of the BRCAPRO model in the clinic is challenging since it requires input of all family history information regarding breast and ovarian cancer. The Tyrer-Cuzick model attempts to utilize both family history information and individual risk information. It uses the family history to calculate the probability that an individual carries a mutation in one of the breast cancer suscep-tibility genes, and then the risk is adjusted based on personal risk factors, including age at menarche, parity, age at first live birth, age at menopause, history of atypical hyperplasia or LCIS, height, and body mass index.59 Once a risk model has been uti-lized to assess breast cancer risk, this must be communicated to the individual and put into context with
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Surgery_Schwartz. history of breast and ovarian cancer.57 The prob-ability that an individual will develop breast or ovarian cancer is derived from this mutation probability based on age-specific incidence curves for both mutation carriers and noncarriers.58 Use of the BRCAPRO model in the clinic is challenging since it requires input of all family history information regarding breast and ovarian cancer. The Tyrer-Cuzick model attempts to utilize both family history information and individual risk information. It uses the family history to calculate the probability that an individual carries a mutation in one of the breast cancer suscep-tibility genes, and then the risk is adjusted based on personal risk factors, including age at menarche, parity, age at first live birth, age at menopause, history of atypical hyperplasia or LCIS, height, and body mass index.59 Once a risk model has been uti-lized to assess breast cancer risk, this must be communicated to the individual and put into context with
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atypical hyperplasia or LCIS, height, and body mass index.59 Once a risk model has been uti-lized to assess breast cancer risk, this must be communicated to the individual and put into context with competing risk and medical comorbidities. This information can then be used to discuss options that are available to the individual for manag-ing risk.Risk ManagementSeveral important medical decisions may be affected by a wom-an’s underlying risk of developing breast cancer.60-68 These deci-sions include when to use postmenopausal hormone replacement therapy, at what age to begin mammography screening or incor-porate magnetic resonance imaging (MRI) screening, when to use tamoxifen to prevent breast cancer, and when to perform prophylactic mastectomy to prevent breast cancer. Postmeno-pausal hormone replacement therapy was widely prescribed in the 1980s and 1990s because of its effectiveness in controlling the symptoms of estrogen deficiency, namely vasomotor symp-toms such as hot flashes,
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Surgery_Schwartz. atypical hyperplasia or LCIS, height, and body mass index.59 Once a risk model has been uti-lized to assess breast cancer risk, this must be communicated to the individual and put into context with competing risk and medical comorbidities. This information can then be used to discuss options that are available to the individual for manag-ing risk.Risk ManagementSeveral important medical decisions may be affected by a wom-an’s underlying risk of developing breast cancer.60-68 These deci-sions include when to use postmenopausal hormone replacement therapy, at what age to begin mammography screening or incor-porate magnetic resonance imaging (MRI) screening, when to use tamoxifen to prevent breast cancer, and when to perform prophylactic mastectomy to prevent breast cancer. Postmeno-pausal hormone replacement therapy was widely prescribed in the 1980s and 1990s because of its effectiveness in controlling the symptoms of estrogen deficiency, namely vasomotor symp-toms such as hot flashes,
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replacement therapy was widely prescribed in the 1980s and 1990s because of its effectiveness in controlling the symptoms of estrogen deficiency, namely vasomotor symp-toms such as hot flashes, night sweats and their associated sleep deprivation, osteoporosis, and cognitive changes. Furthermore, these hormone supplements were thought to reduce coronary artery disease as well. Use of combined estrogen and progester-one became standard for women who had not undergone hyster-ectomy because unopposed estrogen increases the risk of uterine cancer. Concerns of prolonging a woman’s lifetime exposure to estrogen, coupled with conflicting data regarding the impact of these hormones on cardiovascular health, motivated the imple-mentation of large-scale phase 3 clinical trials to definitively evaluate the risks vs. benefits of postmenopausal hormone replacement therapy. The Women’s Health Initiative (WHI) was therefore designed by the National Institutes of Health as a series of clinical trials
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Surgery_Schwartz. replacement therapy was widely prescribed in the 1980s and 1990s because of its effectiveness in controlling the symptoms of estrogen deficiency, namely vasomotor symp-toms such as hot flashes, night sweats and their associated sleep deprivation, osteoporosis, and cognitive changes. Furthermore, these hormone supplements were thought to reduce coronary artery disease as well. Use of combined estrogen and progester-one became standard for women who had not undergone hyster-ectomy because unopposed estrogen increases the risk of uterine cancer. Concerns of prolonging a woman’s lifetime exposure to estrogen, coupled with conflicting data regarding the impact of these hormones on cardiovascular health, motivated the imple-mentation of large-scale phase 3 clinical trials to definitively evaluate the risks vs. benefits of postmenopausal hormone replacement therapy. The Women’s Health Initiative (WHI) was therefore designed by the National Institutes of Health as a series of clinical trials
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the risks vs. benefits of postmenopausal hormone replacement therapy. The Women’s Health Initiative (WHI) was therefore designed by the National Institutes of Health as a series of clinical trials to study the effects of diet, nutritional supplements, and hormones on the risk of cancer, cardiovascular disease, and bone health in postmenopausal women. Findings from primary studies of postmenopausal hormone replacement therapy were released in 2002, demonstrating conclusively that Brunicardi_Ch17_p0541-p0612.indd 55601/03/19 5:04 PM 557THE BREASTCHAPTER 17breast cancer risk is threefold to fourfold higher after >4 years of use and there is no significant reduction in coronary artery or cerebrovascular risks. The Collaborative Group on Hormonal Factors in Breast Cancer combined and reanalyzed data from a number of studies totaling 52,705 women with breast cancer and 108,411 women without breast cancer. They found an increased risk of breast cancer with every use of estrogen
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Surgery_Schwartz. the risks vs. benefits of postmenopausal hormone replacement therapy. The Women’s Health Initiative (WHI) was therefore designed by the National Institutes of Health as a series of clinical trials to study the effects of diet, nutritional supplements, and hormones on the risk of cancer, cardiovascular disease, and bone health in postmenopausal women. Findings from primary studies of postmenopausal hormone replacement therapy were released in 2002, demonstrating conclusively that Brunicardi_Ch17_p0541-p0612.indd 55601/03/19 5:04 PM 557THE BREASTCHAPTER 17breast cancer risk is threefold to fourfold higher after >4 years of use and there is no significant reduction in coronary artery or cerebrovascular risks. The Collaborative Group on Hormonal Factors in Breast Cancer combined and reanalyzed data from a number of studies totaling 52,705 women with breast cancer and 108,411 women without breast cancer. They found an increased risk of breast cancer with every use of estrogen
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and reanalyzed data from a number of studies totaling 52,705 women with breast cancer and 108,411 women without breast cancer. They found an increased risk of breast cancer with every use of estrogen replacement therapy. They also reported increased risk among current users but not past users and risk increased with increasing duration of use of hormone replacement therapy.69 Cheblowski et al also reported from the WHI study that estrogen + progesterone increased the incidence of breast cancer.70 This was con-firmed by the Million Women study, which also showed that the increased risk was substantially greater for the combined estrogen + progesterone replacement therapy than other types of hormone replacement therapy.71Breast Cancer Screening. Routine use of screening mam-mography in women ≥50 years of age has been reported to reduce mortality from breast cancer by 25%.72 This reduc-tion comes at an acceptable economic cost. More recently, there has been debate over the potential
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Surgery_Schwartz. and reanalyzed data from a number of studies totaling 52,705 women with breast cancer and 108,411 women without breast cancer. They found an increased risk of breast cancer with every use of estrogen replacement therapy. They also reported increased risk among current users but not past users and risk increased with increasing duration of use of hormone replacement therapy.69 Cheblowski et al also reported from the WHI study that estrogen + progesterone increased the incidence of breast cancer.70 This was con-firmed by the Million Women study, which also showed that the increased risk was substantially greater for the combined estrogen + progesterone replacement therapy than other types of hormone replacement therapy.71Breast Cancer Screening. Routine use of screening mam-mography in women ≥50 years of age has been reported to reduce mortality from breast cancer by 25%.72 This reduc-tion comes at an acceptable economic cost. More recently, there has been debate over the potential
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women ≥50 years of age has been reported to reduce mortality from breast cancer by 25%.72 This reduc-tion comes at an acceptable economic cost. More recently, there has been debate over the potential harms associated with breast screening.73 Controversy over the age to initiate screening mammography is evident in the current recommendations. The U.S. Preventive Services Task Force (USPSTF), the American Cancer Society (ACS), and the National Comprehensive Cancer Network (NCCN) are three organizations with differing recom-mendations for screening mammography in average risk women. The guidelines, however, similarly define high-risk women as those with personal history of breast cancer, history of chest radiation at young age, and confirmed or suspected genetic mutation known to increase risk for developing breast cancer. The USPSTF recommends biennial screening mammog-raphy for women age 50 to 74 years. The USPSTF applies these guidelines to asymptomatic women age >40 years who do not
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Surgery_Schwartz. women ≥50 years of age has been reported to reduce mortality from breast cancer by 25%.72 This reduc-tion comes at an acceptable economic cost. More recently, there has been debate over the potential harms associated with breast screening.73 Controversy over the age to initiate screening mammography is evident in the current recommendations. The U.S. Preventive Services Task Force (USPSTF), the American Cancer Society (ACS), and the National Comprehensive Cancer Network (NCCN) are three organizations with differing recom-mendations for screening mammography in average risk women. The guidelines, however, similarly define high-risk women as those with personal history of breast cancer, history of chest radiation at young age, and confirmed or suspected genetic mutation known to increase risk for developing breast cancer. The USPSTF recommends biennial screening mammog-raphy for women age 50 to 74 years. The USPSTF applies these guidelines to asymptomatic women age >40 years who do not
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for developing breast cancer. The USPSTF recommends biennial screening mammog-raphy for women age 50 to 74 years. The USPSTF applies these guidelines to asymptomatic women age >40 years who do not have a preexisting breast cancer or who were not previously diagnosed with a high-risk breast lesion, and who are not at high risk for breast cancer because of a known underlying genetic mutation or history of chest radiation at a young age.74-76 In October 2015, the ACS released updated guidelines stating average-risk women should start annual screening mammogra-phy at 45 years of age. Women age 45 to 54 years should be screened annually, and those 55 years and older should transi-tion to biennial screening or have the opportunity to continue annual screening. Women should have the opportunity to begin annual screening between the ages of 40 and 44 years and should continue screening as long as their overall health is good and have a life expectancy of 10 years or longer. The ACS does not
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Surgery_Schwartz. for developing breast cancer. The USPSTF recommends biennial screening mammog-raphy for women age 50 to 74 years. The USPSTF applies these guidelines to asymptomatic women age >40 years who do not have a preexisting breast cancer or who were not previously diagnosed with a high-risk breast lesion, and who are not at high risk for breast cancer because of a known underlying genetic mutation or history of chest radiation at a young age.74-76 In October 2015, the ACS released updated guidelines stating average-risk women should start annual screening mammogra-phy at 45 years of age. Women age 45 to 54 years should be screened annually, and those 55 years and older should transi-tion to biennial screening or have the opportunity to continue annual screening. Women should have the opportunity to begin annual screening between the ages of 40 and 44 years and should continue screening as long as their overall health is good and have a life expectancy of 10 years or longer. The ACS does not
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to begin annual screening between the ages of 40 and 44 years and should continue screening as long as their overall health is good and have a life expectancy of 10 years or longer. The ACS does not recommend clinical breast examination for breast cancer screening among average-risk women at any age.77 The NCCN recommends that average-risk women begin annual screening mammograms at ≥40 years of age, along with annual clinical breast exams and breast awareness.78The United Kingdom recently established an independent expert panel to review the published literature and estimate the benefits and harms associated with screening women >50 years of age in its national screening program.79 The expert panel estimated that an invitation to breast screening delivers about a 20% reduction in breast cancer mortality. At the same time, however, the panel estimated that in women invited to the screening, about 11% of the cancers diagnosed in their lifetime constitute overdiagnosis. Despite the
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Surgery_Schwartz. to begin annual screening between the ages of 40 and 44 years and should continue screening as long as their overall health is good and have a life expectancy of 10 years or longer. The ACS does not recommend clinical breast examination for breast cancer screening among average-risk women at any age.77 The NCCN recommends that average-risk women begin annual screening mammograms at ≥40 years of age, along with annual clinical breast exams and breast awareness.78The United Kingdom recently established an independent expert panel to review the published literature and estimate the benefits and harms associated with screening women >50 years of age in its national screening program.79 The expert panel estimated that an invitation to breast screening delivers about a 20% reduction in breast cancer mortality. At the same time, however, the panel estimated that in women invited to the screening, about 11% of the cancers diagnosed in their lifetime constitute overdiagnosis. Despite the
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cancer mortality. At the same time, however, the panel estimated that in women invited to the screening, about 11% of the cancers diagnosed in their lifetime constitute overdiagnosis. Despite the overdiagnosis, the panel concluded that breast screening confers significant benefit and should continue. The use of screening mammography in women <50 years of age is more controversial for several reasons: (a) breast density is greater, and screening mammography is less likely to detect early breast cancer (i.e., reduced sensitivity); (b) screening mammography results in more false-positive test findings (i.e., reduced specificity), which results in unneces-sary biopsy specimens; and (c) younger women are less likely to have breast cancer (i.e., lower incidence), so fewer young women will benefit from screening.80,81 In the United States, on a population basis, however, the benefits of screening mam-mography in women between the ages of 40 and 49 years is still felt to outweigh the risks;
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Surgery_Schwartz. cancer mortality. At the same time, however, the panel estimated that in women invited to the screening, about 11% of the cancers diagnosed in their lifetime constitute overdiagnosis. Despite the overdiagnosis, the panel concluded that breast screening confers significant benefit and should continue. The use of screening mammography in women <50 years of age is more controversial for several reasons: (a) breast density is greater, and screening mammography is less likely to detect early breast cancer (i.e., reduced sensitivity); (b) screening mammography results in more false-positive test findings (i.e., reduced specificity), which results in unneces-sary biopsy specimens; and (c) younger women are less likely to have breast cancer (i.e., lower incidence), so fewer young women will benefit from screening.80,81 In the United States, on a population basis, however, the benefits of screening mam-mography in women between the ages of 40 and 49 years is still felt to outweigh the risks;
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from screening.80,81 In the United States, on a population basis, however, the benefits of screening mam-mography in women between the ages of 40 and 49 years is still felt to outweigh the risks; although targeting mammography to women at higher risk of breast cancer improves the balance of risks and benefits and is the approach some health care sys-tems have taken. In one study of women age 40 to 49 years, an abnormal mammography finding was three times more likely to be cancer in a woman with a family history of breast cancer than in a woman without such a history. Furthermore, as noted previously in the section Risk Assessment Models, mounting data regarding mammographic breast density demonstrate an independent correlation with breast cancer risk. Incorporation of breast density measurements into breast cancer risk assess-ment models appears to be a promising strategy for increasing the accuracy of these tools. Unfortunately, widespread applica-tion of these modified models is
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Surgery_Schwartz. from screening.80,81 In the United States, on a population basis, however, the benefits of screening mam-mography in women between the ages of 40 and 49 years is still felt to outweigh the risks; although targeting mammography to women at higher risk of breast cancer improves the balance of risks and benefits and is the approach some health care sys-tems have taken. In one study of women age 40 to 49 years, an abnormal mammography finding was three times more likely to be cancer in a woman with a family history of breast cancer than in a woman without such a history. Furthermore, as noted previously in the section Risk Assessment Models, mounting data regarding mammographic breast density demonstrate an independent correlation with breast cancer risk. Incorporation of breast density measurements into breast cancer risk assess-ment models appears to be a promising strategy for increasing the accuracy of these tools. Unfortunately, widespread applica-tion of these modified models is
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into breast cancer risk assess-ment models appears to be a promising strategy for increasing the accuracy of these tools. Unfortunately, widespread applica-tion of these modified models is hampered by inconsistencies in the reporting of mammographic density. Ultrasonography can also be used for breast cancer screening in women with dense breasts, but there is no data available that the additional cancers detected with this modality reduce mortality from breast cancer.Current recommendations by the United States Preventive Services Task Force are that women undergo biennial mammo-graphic screening between the ages of 50 and 74 years.77 The use of MRI for breast cancer screening is recommended by the ACS for women with a 20% to 25% or greater lifetime risk using risk assessment tools based mainly on family history, BRCA mutation carriers, those individuals who have a family member with a BRCA mutation who have not been tested themselves, individuals who received radiation to the chest
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Surgery_Schwartz. into breast cancer risk assess-ment models appears to be a promising strategy for increasing the accuracy of these tools. Unfortunately, widespread applica-tion of these modified models is hampered by inconsistencies in the reporting of mammographic density. Ultrasonography can also be used for breast cancer screening in women with dense breasts, but there is no data available that the additional cancers detected with this modality reduce mortality from breast cancer.Current recommendations by the United States Preventive Services Task Force are that women undergo biennial mammo-graphic screening between the ages of 50 and 74 years.77 The use of MRI for breast cancer screening is recommended by the ACS for women with a 20% to 25% or greater lifetime risk using risk assessment tools based mainly on family history, BRCA mutation carriers, those individuals who have a family member with a BRCA mutation who have not been tested themselves, individuals who received radiation to the chest
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mainly on family history, BRCA mutation carriers, those individuals who have a family member with a BRCA mutation who have not been tested themselves, individuals who received radiation to the chest between the ages of 10 and 30 years, and those individuals with a history of Li-Fraumeni syndrome, Cowden syndrome, or Bannayan-Riley-Ruvalcaba syndrome or those who have a first-degree relative with one of these syndromes. MRI is an extremely sensitive screening tool that is not limited by the density of the breast tissue as mammography is; however, its specificity is moderate, leading to more false-positive events and the increased need for biopsy.Chemoprevention. Tamoxifen, a selective estrogen receptor modulator, was the first drug shown to reduce the incidence of breast cancer in healthy women. There have been four pro-spective studies published evaluating tamoxifen vs. placebo for reducing the incidence of invasive breast cancer for women at increased risk. The largest trial was the
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Surgery_Schwartz. mainly on family history, BRCA mutation carriers, those individuals who have a family member with a BRCA mutation who have not been tested themselves, individuals who received radiation to the chest between the ages of 10 and 30 years, and those individuals with a history of Li-Fraumeni syndrome, Cowden syndrome, or Bannayan-Riley-Ruvalcaba syndrome or those who have a first-degree relative with one of these syndromes. MRI is an extremely sensitive screening tool that is not limited by the density of the breast tissue as mammography is; however, its specificity is moderate, leading to more false-positive events and the increased need for biopsy.Chemoprevention. Tamoxifen, a selective estrogen receptor modulator, was the first drug shown to reduce the incidence of breast cancer in healthy women. There have been four pro-spective studies published evaluating tamoxifen vs. placebo for reducing the incidence of invasive breast cancer for women at increased risk. The largest trial was the
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women. There have been four pro-spective studies published evaluating tamoxifen vs. placebo for reducing the incidence of invasive breast cancer for women at increased risk. The largest trial was the Breast Cancer Preven-tion Trial (NSABP P-01), which randomly assigned >13,000 women with a 5-year Gail relative risk of breast cancer of 1.66% or higher or LCIS to receive tamoxifen or placebo. After a mean follow-up period of 4 years, the incidence of breast cancer was reduced by 49% in the group receiving tamoxifen.60 The decrease was evident only in ER-positive breast cancers with no significant change in ER-negative tumors. The Royal Marsden Hospital Tamoxifen Chemoprevention Trial,78 the Italian Tamox-ifen Prevention Trial,82 and the International Breast Cancer Intervention Study I (IBIS-I) trial all83 showed a reduction in 6Brunicardi_Ch17_p0541-p0612.indd 55701/03/19 5:04 PM 558SPECIFIC CONSIDERATIONSPART IIER-positive breast cancers with the use of tamoxifen compared with
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Surgery_Schwartz. women. There have been four pro-spective studies published evaluating tamoxifen vs. placebo for reducing the incidence of invasive breast cancer for women at increased risk. The largest trial was the Breast Cancer Preven-tion Trial (NSABP P-01), which randomly assigned >13,000 women with a 5-year Gail relative risk of breast cancer of 1.66% or higher or LCIS to receive tamoxifen or placebo. After a mean follow-up period of 4 years, the incidence of breast cancer was reduced by 49% in the group receiving tamoxifen.60 The decrease was evident only in ER-positive breast cancers with no significant change in ER-negative tumors. The Royal Marsden Hospital Tamoxifen Chemoprevention Trial,78 the Italian Tamox-ifen Prevention Trial,82 and the International Breast Cancer Intervention Study I (IBIS-I) trial all83 showed a reduction in 6Brunicardi_Ch17_p0541-p0612.indd 55701/03/19 5:04 PM 558SPECIFIC CONSIDERATIONSPART IIER-positive breast cancers with the use of tamoxifen compared with
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trial all83 showed a reduction in 6Brunicardi_Ch17_p0541-p0612.indd 55701/03/19 5:04 PM 558SPECIFIC CONSIDERATIONSPART IIER-positive breast cancers with the use of tamoxifen compared with placebo. There was no effect on mortality; however, the trials were not powered to assess either breast cancer mortality or all-cause mortality events. The adverse events were similar in all four randomized trials, including an increased risk of endo-metrial cancer, thromboembolic events, cataract formation, and vasomotor disturbances in individuals receiving tamoxifen.Tamoxifen therapy currently is recommended only for women who have a Gail relative risk of 1.66% or higher, who are age 35 to 59, women over the age of 60, or women with a diagnosis of LCIS or atypical ductal or lobular hyperplasia. In addition, deep vein thrombosis occurs 1.6 times as often, pulmonary emboli 3.0 times as often, and endometrial cancer 2.5 times as often in women taking tamoxifen. The increased risk for endometrial
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Surgery_Schwartz. trial all83 showed a reduction in 6Brunicardi_Ch17_p0541-p0612.indd 55701/03/19 5:04 PM 558SPECIFIC CONSIDERATIONSPART IIER-positive breast cancers with the use of tamoxifen compared with placebo. There was no effect on mortality; however, the trials were not powered to assess either breast cancer mortality or all-cause mortality events. The adverse events were similar in all four randomized trials, including an increased risk of endo-metrial cancer, thromboembolic events, cataract formation, and vasomotor disturbances in individuals receiving tamoxifen.Tamoxifen therapy currently is recommended only for women who have a Gail relative risk of 1.66% or higher, who are age 35 to 59, women over the age of 60, or women with a diagnosis of LCIS or atypical ductal or lobular hyperplasia. In addition, deep vein thrombosis occurs 1.6 times as often, pulmonary emboli 3.0 times as often, and endometrial cancer 2.5 times as often in women taking tamoxifen. The increased risk for endometrial
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Surgery_Schwartz_3790
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addition, deep vein thrombosis occurs 1.6 times as often, pulmonary emboli 3.0 times as often, and endometrial cancer 2.5 times as often in women taking tamoxifen. The increased risk for endometrial cancer is restricted to early stage cancers in postmenopausal women. Cataract surgery is required almost twice as often among women taking tamoxifen. Gail et al sub-sequently developed a model that accounts for underlying risk of breast cancer as well as comorbidities to determine the net risk-benefit ratio of tamoxifen use for chemoprevention.84The NSABP completed a second chemoprevention trial, designed to compare tamoxifen and raloxifene for breast cancer risk reduction in high-risk postmenopausal women. Raloxifene, another selective estrogen receptor modulator, was selected for the experimental arm in this follow-up prevention trial because its use in managing postmenopausal osteoporosis suggested that it might be even more effective at breast cancer risk reduc-tion, but without the
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Surgery_Schwartz. addition, deep vein thrombosis occurs 1.6 times as often, pulmonary emboli 3.0 times as often, and endometrial cancer 2.5 times as often in women taking tamoxifen. The increased risk for endometrial cancer is restricted to early stage cancers in postmenopausal women. Cataract surgery is required almost twice as often among women taking tamoxifen. Gail et al sub-sequently developed a model that accounts for underlying risk of breast cancer as well as comorbidities to determine the net risk-benefit ratio of tamoxifen use for chemoprevention.84The NSABP completed a second chemoprevention trial, designed to compare tamoxifen and raloxifene for breast cancer risk reduction in high-risk postmenopausal women. Raloxifene, another selective estrogen receptor modulator, was selected for the experimental arm in this follow-up prevention trial because its use in managing postmenopausal osteoporosis suggested that it might be even more effective at breast cancer risk reduc-tion, but without the
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Surgery_Schwartz_3791
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arm in this follow-up prevention trial because its use in managing postmenopausal osteoporosis suggested that it might be even more effective at breast cancer risk reduc-tion, but without the adverse effects of tamoxifen on the uterus. The P-2 trial, the Study of Tamoxifen and Raloxifene (known as the STAR trial), randomly assigned 19,747 postmenopausal women at high-risk for breast cancer to receive either tamoxi-fen or raloxifene. The initial report of the P-2 trial showed the two agents were nearly identical in their ability to reduce breast cancer risk, but raloxifene was associated with a more favor-able adverse event profile.85 An updated analysis revealed that raloxifene maintained 76% of the efficacy of tamoxifen in pre-vention of invasive breast cancer with a more favorable side effect profile. The risk of developing endometrial cancer was significantly higher with tamoxifen use at longer follow-up.86 Although tamoxifen has been shown to reduce the incidence of LCIS and DCIS,
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Surgery_Schwartz. arm in this follow-up prevention trial because its use in managing postmenopausal osteoporosis suggested that it might be even more effective at breast cancer risk reduc-tion, but without the adverse effects of tamoxifen on the uterus. The P-2 trial, the Study of Tamoxifen and Raloxifene (known as the STAR trial), randomly assigned 19,747 postmenopausal women at high-risk for breast cancer to receive either tamoxi-fen or raloxifene. The initial report of the P-2 trial showed the two agents were nearly identical in their ability to reduce breast cancer risk, but raloxifene was associated with a more favor-able adverse event profile.85 An updated analysis revealed that raloxifene maintained 76% of the efficacy of tamoxifen in pre-vention of invasive breast cancer with a more favorable side effect profile. The risk of developing endometrial cancer was significantly higher with tamoxifen use at longer follow-up.86 Although tamoxifen has been shown to reduce the incidence of LCIS and DCIS,
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Surgery_Schwartz_3792
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profile. The risk of developing endometrial cancer was significantly higher with tamoxifen use at longer follow-up.86 Although tamoxifen has been shown to reduce the incidence of LCIS and DCIS, raloxifene did not have an effect on the frequency of these diagnoses.Aromatase inhibitors (AIs) have been shown to be more effective than tamoxifen in reducing the incidence of contra-lateral breast cancers in postmenopausal women receiving AIs for adjuvant treatment of invasive breast cancer. The MAP.3 trial was the first study to evaluate an AI as a chemopreventive agent in postmenopausal women at high risk for breast cancer. The trial randomized 4560 women to exemestane 25 mg daily vs. placebo for 5 years. After a median follow-up of 35 months, exemestane was shown to reduce invasive breast cancer inci-dence by 65%. Side effect profiles demonstrated more grade II or higher arthritis and hot flashes in patients taking exemestane.87 The IBIS II trial on the other hand, randomized 3864
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Surgery_Schwartz. profile. The risk of developing endometrial cancer was significantly higher with tamoxifen use at longer follow-up.86 Although tamoxifen has been shown to reduce the incidence of LCIS and DCIS, raloxifene did not have an effect on the frequency of these diagnoses.Aromatase inhibitors (AIs) have been shown to be more effective than tamoxifen in reducing the incidence of contra-lateral breast cancers in postmenopausal women receiving AIs for adjuvant treatment of invasive breast cancer. The MAP.3 trial was the first study to evaluate an AI as a chemopreventive agent in postmenopausal women at high risk for breast cancer. The trial randomized 4560 women to exemestane 25 mg daily vs. placebo for 5 years. After a median follow-up of 35 months, exemestane was shown to reduce invasive breast cancer inci-dence by 65%. Side effect profiles demonstrated more grade II or higher arthritis and hot flashes in patients taking exemestane.87 The IBIS II trial on the other hand, randomized 3864
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Surgery_Schwartz_3793
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cancer inci-dence by 65%. Side effect profiles demonstrated more grade II or higher arthritis and hot flashes in patients taking exemestane.87 The IBIS II trial on the other hand, randomized 3864 postmeno-pausal women to either anastrozole, a nonsteroidal aromatase inhibitor, vs. placebo with a further randomization to bisphospho-nate or not based on bone density.88,89 After a median follow-up of 5 years, anastrozole reduced the incidence of invasive breast cancer by about 50%. The trial also had an initial sub-study that looked at the effect of the aromatase inhibitor on cogni-tive function and reported no adverse effects.90 The American Society of Clinical Oncology recommends tamoxifen for chemoprevention in premenopausal or postmenopausal women and consideration for raloxifene or exemestane in postmeno-pausal women who are noted to be at increased risk of breast cancer.91,92 The discussion with an individual patient should include risk assessment and potential risks and benefits
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Surgery_Schwartz. cancer inci-dence by 65%. Side effect profiles demonstrated more grade II or higher arthritis and hot flashes in patients taking exemestane.87 The IBIS II trial on the other hand, randomized 3864 postmeno-pausal women to either anastrozole, a nonsteroidal aromatase inhibitor, vs. placebo with a further randomization to bisphospho-nate or not based on bone density.88,89 After a median follow-up of 5 years, anastrozole reduced the incidence of invasive breast cancer by about 50%. The trial also had an initial sub-study that looked at the effect of the aromatase inhibitor on cogni-tive function and reported no adverse effects.90 The American Society of Clinical Oncology recommends tamoxifen for chemoprevention in premenopausal or postmenopausal women and consideration for raloxifene or exemestane in postmeno-pausal women who are noted to be at increased risk of breast cancer.91,92 The discussion with an individual patient should include risk assessment and potential risks and benefits
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Surgery_Schwartz_3794
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in postmeno-pausal women who are noted to be at increased risk of breast cancer.91,92 The discussion with an individual patient should include risk assessment and potential risks and benefits with each agent.Risk-Reducing Surgery. A retrospective study of women at high risk for breast cancer found that prophylactic mastectomy reduced their risk by >90%.62 However, the effects of prophylac-tic mastectomy on the long-term quality of life are poorly quan-tified. A study involving women who were carriers of a breast cancer susceptibility gene (BRCA) mutation found that the ben-efit of prophylactic mastectomy differed substantially according to the breast cancer risk conferred by the mutations. For women with an estimated lifetime risk of 40%, prophylactic mastec-tomy added almost 3 years of life, whereas for women with an estimated lifetime risk of 85%, prophylactic mastectomy added >5 years of life.66 Domchek et al evaluated a cohort of BRCA1 and 2 mutation carriers who were followed
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Surgery_Schwartz. in postmeno-pausal women who are noted to be at increased risk of breast cancer.91,92 The discussion with an individual patient should include risk assessment and potential risks and benefits with each agent.Risk-Reducing Surgery. A retrospective study of women at high risk for breast cancer found that prophylactic mastectomy reduced their risk by >90%.62 However, the effects of prophylac-tic mastectomy on the long-term quality of life are poorly quan-tified. A study involving women who were carriers of a breast cancer susceptibility gene (BRCA) mutation found that the ben-efit of prophylactic mastectomy differed substantially according to the breast cancer risk conferred by the mutations. For women with an estimated lifetime risk of 40%, prophylactic mastec-tomy added almost 3 years of life, whereas for women with an estimated lifetime risk of 85%, prophylactic mastectomy added >5 years of life.66 Domchek et al evaluated a cohort of BRCA1 and 2 mutation carriers who were followed
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life, whereas for women with an estimated lifetime risk of 85%, prophylactic mastectomy added >5 years of life.66 Domchek et al evaluated a cohort of BRCA1 and 2 mutation carriers who were followed prospectively and reported on outcomes with risk-reducing surgery.93 They found that risk-reducing mastectomy was highly effective at preventing breast cancer in both BRCA1 and 2 mutation carriers. Risk-reducing salpingo-oophorectomy was highly effective at reducing the incidence of ovarian cancer and breast cancer in BRCA mutation carriers and was associated with a reduction in breast cancer-specific mortality, ovarian cancer-specific mor-tality, and all-cause mortality. While studies of bilateral pro-phylactic or risk-reducing mastectomy have reported dramatic reductions in breast cancer incidence among those without known BRCA mutations, there is little data to support a survival benefit. Another consideration is that while most patients are satisfied with their decision to pursue
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Surgery_Schwartz. life, whereas for women with an estimated lifetime risk of 85%, prophylactic mastectomy added >5 years of life.66 Domchek et al evaluated a cohort of BRCA1 and 2 mutation carriers who were followed prospectively and reported on outcomes with risk-reducing surgery.93 They found that risk-reducing mastectomy was highly effective at preventing breast cancer in both BRCA1 and 2 mutation carriers. Risk-reducing salpingo-oophorectomy was highly effective at reducing the incidence of ovarian cancer and breast cancer in BRCA mutation carriers and was associated with a reduction in breast cancer-specific mortality, ovarian cancer-specific mor-tality, and all-cause mortality. While studies of bilateral pro-phylactic or risk-reducing mastectomy have reported dramatic reductions in breast cancer incidence among those without known BRCA mutations, there is little data to support a survival benefit. Another consideration is that while most patients are satisfied with their decision to pursue
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Surgery_Schwartz_3796
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incidence among those without known BRCA mutations, there is little data to support a survival benefit. Another consideration is that while most patients are satisfied with their decision to pursue risk-reducing surgery, some are dissatisfied with the cosmetic outcomes mostly due to reconstructive issues.BRCA MutationsBRCA1. Up to 5% of breast cancers are caused by inheritance of germline mutations such as BRCA1 and BRCA2, which are inherited in an autosomal dominant fashion with varying degrees of penetrance (Table 17-7).94-100 BRCA1 is located on chromosome arm 17q, spans a genomic region of approximately 100 kilobases (kb) of DNA, and contains 22 coding exons for 1863 amino acids. Both BRCA1 and BRCA2 function as tumor-suppressor genes, and for each gene, loss of both alleles is required for the initiation of cancer. Data accumulated since the isolation of the BRCA1 gene suggest a role in transcription, cell-cycle control, and DNA damage repair pathways. More than 500 sequence
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Surgery_Schwartz. incidence among those without known BRCA mutations, there is little data to support a survival benefit. Another consideration is that while most patients are satisfied with their decision to pursue risk-reducing surgery, some are dissatisfied with the cosmetic outcomes mostly due to reconstructive issues.BRCA MutationsBRCA1. Up to 5% of breast cancers are caused by inheritance of germline mutations such as BRCA1 and BRCA2, which are inherited in an autosomal dominant fashion with varying degrees of penetrance (Table 17-7).94-100 BRCA1 is located on chromosome arm 17q, spans a genomic region of approximately 100 kilobases (kb) of DNA, and contains 22 coding exons for 1863 amino acids. Both BRCA1 and BRCA2 function as tumor-suppressor genes, and for each gene, loss of both alleles is required for the initiation of cancer. Data accumulated since the isolation of the BRCA1 gene suggest a role in transcription, cell-cycle control, and DNA damage repair pathways. More than 500 sequence
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Surgery_Schwartz_3797
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for the initiation of cancer. Data accumulated since the isolation of the BRCA1 gene suggest a role in transcription, cell-cycle control, and DNA damage repair pathways. More than 500 sequence variations in BRCA1 have been identified. It now is known that germline mutations in BRCA1 represent a predisposing genetic factor in as many as 45% of hereditary breast cancers and in at least 80% of hereditary ovarian cancers. Female mutation carriers have been reported to have up to an 85% lifetime risk (for some families) for developing breast cancer and up to a 40% lifetime risk for developing ovarian cancer. The initial families reported had high penetrance and subsequently the average lifetime risk has been reported to lie between 60% and 70%. Breast cancer susceptibility in these families appears as an autosomal dominant trait with high pen-etrance. Approximately 50% of children of carriers inherit the trait. In general, BRCA1-associated breast cancers are invasive ductal carcinomas, are
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Surgery_Schwartz. for the initiation of cancer. Data accumulated since the isolation of the BRCA1 gene suggest a role in transcription, cell-cycle control, and DNA damage repair pathways. More than 500 sequence variations in BRCA1 have been identified. It now is known that germline mutations in BRCA1 represent a predisposing genetic factor in as many as 45% of hereditary breast cancers and in at least 80% of hereditary ovarian cancers. Female mutation carriers have been reported to have up to an 85% lifetime risk (for some families) for developing breast cancer and up to a 40% lifetime risk for developing ovarian cancer. The initial families reported had high penetrance and subsequently the average lifetime risk has been reported to lie between 60% and 70%. Breast cancer susceptibility in these families appears as an autosomal dominant trait with high pen-etrance. Approximately 50% of children of carriers inherit the trait. In general, BRCA1-associated breast cancers are invasive ductal carcinomas, are
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Surgery_Schwartz_3798
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Surgery_Schwartz
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as an autosomal dominant trait with high pen-etrance. Approximately 50% of children of carriers inherit the trait. In general, BRCA1-associated breast cancers are invasive ductal carcinomas, are poorly differentiated, are in the majority Brunicardi_Ch17_p0541-p0612.indd 55801/03/19 5:04 PM 559THE BREASTCHAPTER 17Table 17-7Incidence of sporadic, familial, and hereditary breast cancerSporadic breast cancer65%–75%Familial breast cancer20%–30%Hereditary breast cancer5%–10% BRCA1a45% BRCA235% p53a (Li-Fraumeni syndrome)1% STK11/LKB1a (Peutz-Jeghers syndrome)<1% PTENa (Cowden disease)<1% MSH2/MLH1a (Muir-Torre syndrome)<1% ATMa (Ataxia-telangiectasia)<1% Unknown20%aAffected gene.Data from Martin AM, Weber BL: Genetic and hormonal risk factors in breast cancer, J Natl Cancer Inst. 2000 Jul 19;92(14):1126-1135.hormone receptor negative, and have a triple receptor negative (immunohistochemical profile: ER-negative, PR-negative, and HER2-negative) or basal phenotype (based on gene
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Surgery_Schwartz. as an autosomal dominant trait with high pen-etrance. Approximately 50% of children of carriers inherit the trait. In general, BRCA1-associated breast cancers are invasive ductal carcinomas, are poorly differentiated, are in the majority Brunicardi_Ch17_p0541-p0612.indd 55801/03/19 5:04 PM 559THE BREASTCHAPTER 17Table 17-7Incidence of sporadic, familial, and hereditary breast cancerSporadic breast cancer65%–75%Familial breast cancer20%–30%Hereditary breast cancer5%–10% BRCA1a45% BRCA235% p53a (Li-Fraumeni syndrome)1% STK11/LKB1a (Peutz-Jeghers syndrome)<1% PTENa (Cowden disease)<1% MSH2/MLH1a (Muir-Torre syndrome)<1% ATMa (Ataxia-telangiectasia)<1% Unknown20%aAffected gene.Data from Martin AM, Weber BL: Genetic and hormonal risk factors in breast cancer, J Natl Cancer Inst. 2000 Jul 19;92(14):1126-1135.hormone receptor negative, and have a triple receptor negative (immunohistochemical profile: ER-negative, PR-negative, and HER2-negative) or basal phenotype (based on gene
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Surgery_Schwartz_3799
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Jul 19;92(14):1126-1135.hormone receptor negative, and have a triple receptor negative (immunohistochemical profile: ER-negative, PR-negative, and HER2-negative) or basal phenotype (based on gene expression profiling). BRCA1-associated breast cancers have a number of distinguishing clinical features, such as an early age of onset compared with sporadic cases; a higher prevalence of bilateral breast cancer; and the presence of associated cancers in some affected individuals, specifically ovarian cancer and possibly colon and prostate cancers.Several founder mutations have been identified in BRCA1. The two most common mutations are 185delAG and 5382insC, which account for 10% of all the mutations seen in BRCA1. These two mutations occur at a 10-fold higher frequency in the Ashkenazi Jewish population than in non-Jewish Caucasians. The carrier frequency of the 185delAG mutation in the Ashkenazi Jewish population is 1% and, along with the 5382insC mutation, accounts for almost all BRCA1
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Surgery_Schwartz. Jul 19;92(14):1126-1135.hormone receptor negative, and have a triple receptor negative (immunohistochemical profile: ER-negative, PR-negative, and HER2-negative) or basal phenotype (based on gene expression profiling). BRCA1-associated breast cancers have a number of distinguishing clinical features, such as an early age of onset compared with sporadic cases; a higher prevalence of bilateral breast cancer; and the presence of associated cancers in some affected individuals, specifically ovarian cancer and possibly colon and prostate cancers.Several founder mutations have been identified in BRCA1. The two most common mutations are 185delAG and 5382insC, which account for 10% of all the mutations seen in BRCA1. These two mutations occur at a 10-fold higher frequency in the Ashkenazi Jewish population than in non-Jewish Caucasians. The carrier frequency of the 185delAG mutation in the Ashkenazi Jewish population is 1% and, along with the 5382insC mutation, accounts for almost all BRCA1
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Surgery_Schwartz_3800
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Surgery_Schwartz
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population than in non-Jewish Caucasians. The carrier frequency of the 185delAG mutation in the Ashkenazi Jewish population is 1% and, along with the 5382insC mutation, accounts for almost all BRCA1 mutations in this population. Analysis of germline mutations in Jewish and non-Jewish women with early-onset breast cancer indicates that 20% of Jewish women who develop breast cancer before age 40 years carry the 185delAG mutation. There are founder BRCA1 mutations in other populations including, among others, Dutch, Polish, Finnish, and Russian populations.101-105BRCA2. BRCA2 is located on chromosome arm 13q and spans a genomic region of approximately 70 kb of DNA. The 11.2-kb coding region contains 26 coding exons.94-100 It encodes a pro-tein of 3418 amino acids. The BRCA2 gene bears no homology to any previously described gene, and the protein contains no previously defined functional domains. The biologic function of BRCA2 is not well defined, but like BRCA1, it is postulated to play
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Surgery_Schwartz. population than in non-Jewish Caucasians. The carrier frequency of the 185delAG mutation in the Ashkenazi Jewish population is 1% and, along with the 5382insC mutation, accounts for almost all BRCA1 mutations in this population. Analysis of germline mutations in Jewish and non-Jewish women with early-onset breast cancer indicates that 20% of Jewish women who develop breast cancer before age 40 years carry the 185delAG mutation. There are founder BRCA1 mutations in other populations including, among others, Dutch, Polish, Finnish, and Russian populations.101-105BRCA2. BRCA2 is located on chromosome arm 13q and spans a genomic region of approximately 70 kb of DNA. The 11.2-kb coding region contains 26 coding exons.94-100 It encodes a pro-tein of 3418 amino acids. The BRCA2 gene bears no homology to any previously described gene, and the protein contains no previously defined functional domains. The biologic function of BRCA2 is not well defined, but like BRCA1, it is postulated to play
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Surgery_Schwartz_3801
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Surgery_Schwartz
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to any previously described gene, and the protein contains no previously defined functional domains. The biologic function of BRCA2 is not well defined, but like BRCA1, it is postulated to play a role in DNA damage response pathways. BRCA2 mes-senger RNA also is expressed at high levels in the late G1 and S phases of the cell cycle. The kinetics of BRCA2 protein regu-lation in the cell cycle is similar to that of BRCA1 protein, which suggests that these genes are coregulated. The mutational spec-trum of BRCA2 is not as well established as that of BRCA1. To date, >250 mutations have been found. The breast cancer risk for BRCA2 mutation carriers is close to 85%, and the life-time ovarian cancer risk, while lower than for BRCA1, is still estimated to be close to 20%. Breast cancer susceptibility in BRCA2 families is an autosomal dominant trait and has a high penetrance. Approximately 50% of children of carriers inherit the trait. Unlike male carriers of BRCA1 mutations, men with
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Surgery_Schwartz. to any previously described gene, and the protein contains no previously defined functional domains. The biologic function of BRCA2 is not well defined, but like BRCA1, it is postulated to play a role in DNA damage response pathways. BRCA2 mes-senger RNA also is expressed at high levels in the late G1 and S phases of the cell cycle. The kinetics of BRCA2 protein regu-lation in the cell cycle is similar to that of BRCA1 protein, which suggests that these genes are coregulated. The mutational spec-trum of BRCA2 is not as well established as that of BRCA1. To date, >250 mutations have been found. The breast cancer risk for BRCA2 mutation carriers is close to 85%, and the life-time ovarian cancer risk, while lower than for BRCA1, is still estimated to be close to 20%. Breast cancer susceptibility in BRCA2 families is an autosomal dominant trait and has a high penetrance. Approximately 50% of children of carriers inherit the trait. Unlike male carriers of BRCA1 mutations, men with
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