Treza12/BreastCancer · Datasets at Hugging Face

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Breast Anatomy and Development	MORPHOLOGY	Microanatomy of Breast Development	null	Lobules develop during the first few years after men- arche. The alveolar buds cluster around a terminal duct and form type I (virginal) lobules, comprising approximately 11 alveolar buds lined by two layers of epithelium. Full differ- entiation of the mammary gland proceeds through puberty, takes many years, and may not be fully completed if inter- rupted by pregnancies.
Breast Anatomy and Development	MORPHOLOGY	Microanatomy of Breast Development	null	Detailed microanatomic studies of the breast have shown the presence of three distinct types of lobules (55). Type I lobules, previously described, are the first genera- tion of lobules that develop just after the menarche. The transition to type II and type III gradually results from con- tinued sprouting of new alveolar buds. The characteristics of the four lobular types are described in Tables 1-3 and 1-4.
Breast Anatomy and Development	MORPHOLOGY	Microanatomy of Breast Development	null	Russo et al. (56) recently determined that the breast tissue of women with invasive cancer and those with a famil- ial pattern of breast cancer have an architectural pattern dif- ferent from the control group of normal tissue. They also found that the BRCA1 or related genes may have a functional role in the branching pattern of the breast during lobular development. This is seen mainly in the epithelial stroma interaction.
Breast Anatomy and Development	MORPHOLOGY	Microscopic Anatomy of the Adult Breast	null	In the immature breast, the ducts and alveoli are lined by a two-layer epithelium that consists of a basal cuboidal layer and a flattened surface layer. In the presence of estrogens at puberty and subsequently, this epithelium proliferates, becoming multilayered in the adult breast (Figs. 1-5 and 1-6). Three alveolar cell types have been observed: superficial (luminal) A cells, basal B cells (chief cells), and myoepithe- lial cells.
Breast Anatomy and Development	MORPHOLOGY	Microscopic Anatomy of the Adult Breast	null	Superficial, or luminal, A cells are dark, basophilic- staining cells that are rich in ribosomes. Superficial cells undergo intercellular dehiscence, with swelling of the mitochondria, and become grouped, forming buds within the lumen. Basal B cells, or chief cells, are the major cell type in mammary epithelium. They are clear, with an ovoid nucleus without nucleoli. Where the basal cells are in con- tact with the lumen, microvilli occur on the cell membrane. Intracytoplasmic filaments are similar to those in myoepi- thelial cells, suggesting their differentiation toward that cell type. Myoepithelial cells are located around alveoli and small excretory milk ducts between the inner aspect of the basement membrane and the tunica propria. Myoepithelial cells are arranged in a branching, star-like fashion. The sar- coplasm contains filaments that are 50 to 80 nm in diam- eter; these myofilaments are inserted by hemidesmosomes into the basal membrane. These cells are not innervated but are stimulated by the steroid hormones prolactin and oxytocin.
Breast Anatomy and Development	MORPHOLOGY	Anatomy of the Nipple and Breast Ducts	null	Recent advances exploring ductal lavage (57) and direct visualization of the ducts with breast endoscopy (58) have made the anatomy of the nipple clinically relevant. Utilizing six different approaches to examine the duc- tal anatomy, Love and Barsky (59) found that more than 90% of all nipples examined contained five to nine duc- tal orifices, generally arranged as a central group and a peripheral group. The central ducts did not extend in a radial fashion from the nipple as previously thought but traveled back from the nipple toward the chest wall. They also found that each nipple orifice communicated with a
Breast Anatomy and Development	MORPHOLOGY	Anatomy of the Nipple and Breast Ducts	null	separate, nonanastomosing ductal system, which extended to the terminal duct lobular unit. Rusby et al. (60) prospec- tively examined nipples from mastectomy specimens. The median number of ducts was 23, but they found far fewer ductal orifices on the nipple surface. This study demon- strates that many ducts share a few common openings on the nipple surface and explains the discrepancy between the number of ductal openings on the nipple and the num- ber of actual ducts.
Breast Anatomy and Development	MORPHOLOGY	Anatomy of the Nipple and Breast Ducts	null	There is evidence to suggest that both ductal and lobu- lar carcinoma arises in the terminal duct lobular unit. Stolier and Wang (61) examined 32 nipples of mastectomy speci- mens. In 29 of the specimens, there were no terminal duct lobular units identified. Three of the 32 specimens were found to have terminal duct lobular units. All terminal duct lobular units were found at the base of the nipple as opposed to near the tip. As interest in intraductal approaches and treatment increases, so too will knowledge of ductal and nipple anatomy.
Breast Anatomy and Development	MORPHOLOGY	Anatomy of the Nipple and Breast Ducts	null	FIGURE 1-5 Normal lobule in adult female breast. The lobule is the functional unit of the breast. It is lined by two cell layers: inner epithelial layer and outer myoepithelial layer. The latter are inconspicuous on routine hematoxylin and eosin (H&E) stain such as this. (Photomicrograph cour- tesy of Dr. Syed Hoda.)
Breast Anatomy and Development	MORPHOLOGY	Anatomy of the Nipple and Breast Ducts	null	FIGURE 1-6 Normal lobule in adult female breast. p63 immunostain highlights the nuclei of the outer myoepithe- lial cell layer of the lobule. (Photomicrograph courtesy of Dr. Syed Hoda.)
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	Histologic changes in the normal breast have been identified in relation to the endocrine variations of the menstrual cycle
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	(62). Normal menstrual cycle–dependent histologic changes in both stroma and epithelium have been observed.
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	Cyclic changes in the sex steroid hormone levels during the menstrual cycle profoundly influence breast morphol- ogy. Under the influence of follicle-stimulating hormone and luteinizing hormone during the follicular phase of the men- strual cycle, increasing levels of estrogen secreted by the ovarian graafian follicles stimulate breast epithelial prolifera- tion. During this proliferative phase, the epithelium exhibits sprouting, with increased cellular mitoses, RNA synthesis, increased nuclear density, enlargement of the nucleolus, and changes in other intercellular organelles. In particular, the Golgi apparatus, ribosomes, and mitochondria increase in size or number. During the follicular phase, at the time of maximal estrogen synthesis and secretion in midcycle, ovu- lation occurs. A second peak occurs in the midluteal phase, when luteal progesterone synthesis is maximal. Similarly, progestogens induce changes in the mammary epithelium during the luteal phase of the ovulatory cycles. Mammary ducts dilate, and the alveolar epithelial cells differentiate into secretory cells, with a partly monolayer arrangement. The combination of these sex steroid hormones and other hormones results in the formation of lipid droplets in the alveolar cells and some intraluminal secretion.
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	The changes in breast epithelium in response to hor- mones are mediated through either intracellular steroid receptors or membrane-bound peptide receptors. The pres- ence of steroid receptors for estrogen and progestogens in the cytosol of normal mammary epithelium has been demon- strated (63). Through the binding of these hormones to spe- cific receptors, the molecular changes, with their observed morphologic effects, are induced as physiologic changes. Similarly, membrane receptors are present to mediate the actions of prolactin. Increases in endogenous estrogen can also exert a histamine-like effect on the mammary microcir- culation (64), resulting in an increased blood flow 3 to 4 days
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	before menstruation, with an average increase in breast volume of 15 to 30 cm3. Premenstrual breast fullness is attributable to increasing interlobular edema and enhanced ductular–acinar proliferation under the influence of estro- gens and progestogens. With the onset of menstruation, after a rapid decline in the circulating levels of sex steroid hormones, secretory activity of the epithelium regresses.
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	Postmenstrually, tissue edema is reduced, and regres- sion of the epithelium ceases as a new cycle begins, with concomitant rises in estrogen levels. Minimum breast vol- ume is observed 5 to 7 days after menstruation. The cyclic changes in breast cellular growth rates are related to hor- monal variations in the follicular and luteal phases of the menstrual cycle. Measurement of these changes can be made by observation and measurement of a variety of cel- lular and nuclear parameters:
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	Histologic pattern
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	Cellular morphology
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	Nuclear morphology
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	Mitoses
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	Tritiated thymidine uptake
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	Image cytometry
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	Nuclear area
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	Circumference
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	Boundary fluctuation
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	Chromatin granularity
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	Stain intensity
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	Proliferation markers
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	Ki-67
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	Proliferating cell nuclear antigen
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	MIB1
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	Most observations have been made from surgical speci- mens, which are usually from women with breast abnor- malities, or from autopsy specimens, which may have resulted in inconsistent and contradictory results.
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	Most studies have shown that breast epithelial cell pro- liferation increases in the second half (luteal phase) of the menstrual cycle (65–71).
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	A study of nuclear tritiated thymidine uptake in surgi- cally excised breast tissue showed that peak uptake was during the luteal phase on days 22 to 24, coinciding with an increase in circulatory progesterone levels and a second peak of estrogen. The role of estrogen was considered unim- portant because the preovulatory peak of estrogen was not associated with an increase in tritiated thymidine uptake
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	(67). The possibility of a synergistic action between estro- gen and progesterone would therefore be unlikely.
Breast Anatomy and Development	PHYSIOLOGY	Microscopy, Morphology, and the Menstrual Cycle	null	The role of estrogen and progesterone was subsequently studied in explants of human breast tissue implanted sub- cutaneously in nude mice (72). An increase in epithelial cell growth was observed 7 days after exposure to estrogen; pro- gesterone had no effect, and a combination of estrogen and progesterone neither enhanced nor diminished the prolifera- tive effect of estrogen. These observations may explain why proliferation increases during the luteal phase subsequent to the preovulatory estrogen peak.
Breast Anatomy and Development	PHYSIOLOGY	Breast Changes during Pregnancy	null	During pregnancy, marked ductular, lobular, and alveolar growth occurs as a result of the influence of luteal and placental sex steroids, placental lactogen, prolactin, and chorionic gonadotropin (Fig. 1-4B). In experimental studies, these effects are observed when estrogen and progesterone cause a release of prolactin by reducing the hypothalamic release of prolactin-inhibiting factor (PIF) (69). Prolactin in humans is also released progressively during pregnancy and probably stimulates epithelial growth and secretion
Breast Anatomy and Development	PHYSIOLOGY	Breast Changes during Pregnancy	null	(70,71). Prolactin increases slowly during the first half of pregnancy; during the second and third trimesters, blood levels of prolactin are three to five times higher than nor- mal, and mammary epithelium initiates protein synthesis.
Breast Anatomy and Development	PHYSIOLOGY	Breast Changes during Pregnancy	null	In the first 3 to 4 weeks of pregnancy, marked ductular sprouting occurs with some branching, and lobular formation occurs under estrogenic influence. At 5 to 8 weeks, breast enlargement is significant, with dilatation of the superficial veins, heaviness, and increasing pigmentation of the nipple– areolar complex. In the second trimester, lobular formation exceeds ductular sprouting under progestogenic influence. The alveoli contain colostrum but no fat, which is secreted under the influence of prolactin. From the second half of preg- nancy onward, increasing breast size results not from mam- mary epithelial proliferation but from increasing dilatation of the alveoli with colostrum, as well as from hypertrophy of myoepithelial cells, connective tissue, and fat. If these pro- cesses are interrupted by early delivery, lactation may be adequate from 16 weeks of pregnancy onward.
Breast Anatomy and Development	PHYSIOLOGY	Breast Changes during Pregnancy	null	At the beginning of the second trimester, the mammary alveoli, but not the milk ducts, lose the superficial layer of A cells. Before this, as in the nonpregnant woman, the two- layer structure is maintained. In the second and third trimes- ters, this monolayer differentiates into a colostrum–cell layer and accumulates eosinophilic cells, plasma cells, and leuko- cytes around the alveoli. As pregnancy continues, colostrum, composed of desquamated epithelial cells, accumulates. Aggregations of lymphocytes, round cells, and desquamated phagocytic alveolar cells (foam cells) may be found in colos- trum; these are termed the Donné corpuscles.
Breast Anatomy and Development	PHYSIOLOGY	Lactation	null	After parturition, an immediate withdrawal of placental lac- togen and sex steroid hormones occurs. During pregnancy, these hormones antagonize the effect of prolactin on mam- mary epithelium. Concomitant to the abrupt removal of the placental hormones, luteal production of the sex steroid hor- mones also ceases. A nadir is reached on the fourth to fifth day postpartum; at this time, the secretion of PIF from the hypothalamus into the hypothalamoadenohypophyseal por- tal system decreases. This reduction in PIF secretion allows the transmembrane secretion of prolactin by pituitary lacto- trophs. Sex steroid hormones are not necessary for successful lactation, and physiologic increases, such as may occur with postpartum ovulatory cycles, do not inhibit it.
Breast Anatomy and Development	PHYSIOLOGY	Lactation	null	Prolactin, in the presence of growth hormone, insulin, and cortisol, converts the mammary epithelial cells from a presecretory to a secretory state. During the first 4 or 5 days after giving birth, the breasts enlarge as a result of the accu- mulation of secretions in the alveoli and ducts (Fig. 1-7). The initial secretion is of colostrum, a thin, serous fluid that is, at first, sticky and yellow. Colostrum contains lactoglobulin, which is identical to blood immunoglobulins. The importance of these immunoglobulins is unknown; many maternal anti- bodies cross the placenta, transferring passive immunity to the fetus in utero. Fatty acids such as decadienoic acid, phos- pholipids, fat-soluble vitamins, and lactalbumin in colostrum have considerable nutritional value. After colostrum secre- tion, transitional milk and then mature milk are elaborated.
Breast Anatomy and Development	PHYSIOLOGY	Lactation	Mechanisms of Milk Synthesis and Secretion	The effects of prolactin are mediated through membrane receptors in the mammary epithelial cells. The release of prolactin is maintained and stimulated by suckling, as is the release of corticotrophin (adrenocorticotropic hormone). The mammary cells are cuboidal, depending on the degree of intracellular accumulation of secretions. The DNA and RNA of the nuclei increase, and abundant mitochondria,
Breast Anatomy and Development	PHYSIOLOGY	Lactation	Mechanisms of Milk Synthesis and Secretion	FIGURE 1-7 Lactating breast tissue. The glands within the lobules are enlarged and dilated. The stroma within the lobule is diminished. Secretory vacuoles are present within
Breast Anatomy and Development	PHYSIOLOGY	Lactation	Mechanisms of Milk Synthesis and Secretion	the individual lobular epithelial cells. Hematoxylin and eosin (H&E) stain. (Photomicrograph courtesy of Dr. Syed Hoda.)
Breast Anatomy and Development	PHYSIOLOGY	Lactation	Mechanisms of Milk Synthesis and Secretion	ribosomes, and rough endoplasmic reticulum, with a promi- nent Golgi apparatus, are apparent in the epithelial cells. Complex protein, mild fat, and lactose synthetic pathways are activated, as are water–ion transport mechanisms. These processes are initiated by the activation of hormone-specific membrane receptors. Changes in cyclic adenosine mono- phosphate stimulate milk synthesis through the induction of messenger and transfer RNA. Prolactin stimulates cyclic adenosine monophosphate–induced protein kinase activity, resulting in the phosphorylation of milk proteins. Polymerase activity and cellular transcription are enhanced (17).
Breast Anatomy and Development	PHYSIOLOGY	Lactation	Mechanisms of Milk Synthesis and Secretion	Large fat vacuoles develop and move toward the apex of the cell. At the same time, the nucleus also moves toward the apex. As the water intake of the cell increases, longitudinal cellular striations may be observed. Ultimately, the vacuoles pass from the cell along with part of the cell membrane and cytoplasm; the apical cell membrane reconstitutes as secretion takes place.
Breast Anatomy and Development	PHYSIOLOGY	Lactation	Mechanisms of Milk Synthesis and Secretion	FIGURE 1-8 Atrophic breast tissue in a postmenopausal woman. Only a few atrophic ducts and lobules are present amid dense fibrous and fatty tissue. Hematoxylin and eosin (H&E) stain. (Photomicrograph courtesy of Dr. Syed Hoda.)
Breast Anatomy and Development	PHYSIOLOGY	Lactation	Mechanisms of Milk Synthesis and Secretion	Enhanced activity occurs during suckling. Fat is secreted chiefly through an apocrine mechanism, lactose is secreted through a merocrine mechanism, and the secretion of pro- teins occurs as a result of a combination of mechanisms. Ions enter the milk by diffusion and active transport. Relatively little holocrine secretion is thought to take place. The end result of secretion and subsequent intraductal dilution of extracellular fluid is milk, comprising a suspension of pro- teins—casein, -lactalbumin, and -lactoglobulin—and fat in a lactose–mineral solution. The white appearance of milk is due to emulsified lipids and calcium caseinate, whereas the yel- low color of butterfat is due to the presence of carotenoids.
Breast Anatomy and Development	PHYSIOLOGY	Lactation	Mechanisms of Milk Ejection	The removal of milk by suckling is aided by active ejection. Sensory nerve endings in the nipple–areolar complex are activated by tactile stimuli. Impulses pass by way of sensory nerves through the dorsal roots to the spinal cord. In the spinal cord, impulses are relayed through the dorsal, lateral, and ventral spinothalamic tracts to the mesencephalon and lateral hypothalamus. Inhibition of PIF secretion permits the unimpeded secretion of prolactin from the anterior pitu- itary. Simultaneously, through a different pathway in the paraventricular nucleus, the synthesis of oxytocin occurs. Oxytocin is released from the posterior pituitary neu- rovesicles by impulses traveling along the neurosecretory fibers of the hypothalamoneurohypophyseal tract. Oxytocin released into the systemic circulation acts on the myoepi- thelial cells, which contract and eject milk from the alveoli into the lactiferous ducts and sinuses. This phenomenon is specific to oxytocin, and changes in intramammary ductal pressures of 20 to 25 mm Hg may be observed in relation to peak blood levels. Oxytocin also acts on the uterus and cervix to promote involution. This effect may be stimulated by cervical dilatation and by vaginal stretching through the ascending afferent neural pathways (Ferguson reflex).
Breast Anatomy and Development	PHYSIOLOGY	Lactation	Mechanisms of Milk Ejection	Complex neuroendocrine interactions determine normal lactation. An appreciation of these mechanisms is essential to the understanding of abnormalities and to the treatment of problems of lactation (17).
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Menopause is the result of the atresia of more than 400,000 follicles that are present in the ovaries of a female fetus at 5 months’ gestation. Declining ovarian function in late pre- menopause through the menopause leads to regression of epithelial structures and stroma. Menopausal involution of the breast results in reduction of both the number of ducts and lobules. Stromal changes dominate and fat deposition increases while the regression of connective tissue continues. The duct system remains, but the lobules shrink and collapse (Fig. 1-8). Lymphatic channels are also reduced in number in the postmenopausal breast (36). The last structures to appear with sexual maturity are the first ones to regress (17).
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	REFERENCES
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Hamilton NJ, Boyd JD, Mossman HW. Human embryology. Cambridge: Heffer 1968:428.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Cardiff RD, Wellings SR. The comparative pathology of human and mouse mammary glands. J Mammary Gland Biol Neoplasia 1999;4:105.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Hughes ESR. Development of the mammary gland. Ann R Coll Surg Engl
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	1950;6:99.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Dawson EK. A histological study of the normal mamma in relation to tumour growth: I. Early development to maturity. Edinb Med J 1934;41:653.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Moffat DF, Going JJ. Three dimensional anatomy of complete duct sys- tems in human breast: pathological and developmental implications. J Clin Pathol 1996;49:48.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Mimoumi R, Merlob P, Reisner SH. Occurrence of supernumerary nipples in newborns. Am J Dis Children 1983;137:952.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Urbani CE, Betti R. Accessory mammary tissue associated with congenital and hereditary nephrourinary malformations. Int J Dermatol 1996;35:349.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Grotto I, Browner-Elhanan K, Mimouni D, et al. Occurrence of supernu- merary nipples in children with kidney and urinary tract malformations. Pediatr Dermatol 2001;40:637.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Jojart G, Seres E. Supernumerary nipple and renal anomalies. Int Urol Nephrol 1994;26:141.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Maliniac JW. Breast deformities and their origin. New York: Grune & Stratton 1950:163.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Simon BE, Hoffman S, Kahn S. Treatment of asymmetry of the breasts. Clin Plast Surg 1975;2:375.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Trier WC. Complete breast absence. Plast Reconstr Surg 1965;36:430.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Pers M. Aplasias of the anterior thoracic wall, the pectoral muscle, and the breast. Scand J Plast Reconstr Surg 1968;2:125.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Beals RK, Crawford S. Congenital absence of the pectoral muscles. Clin Orthop 1976;119:166.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	McDowell F. On the propagation, perpetuation and parroting of erroneous eponyms such as “Poland’s syndrome.” Plast Reconstr Surg 1977;59:561.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Ravitch MM. Poland’s syndrome: a study of an eponym. Plast Reconstr Surg
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	1977;59:508.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Vorherr H. The breast: morphology, physiology and lactation. New York: Academic Press 1974.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Tanner JM. Wachstun und Reifung des Menschen. Stuttgart: Georg Thieme Verlag 1962.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Parks AG. The micro-anatomy of the breast. Ann R Coll Surg Engl 1959;25:235.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Spratt JS. Anatomy of the breast. Major Probl Clin Surg 1979;5:1.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Bonsor GM, Dossett JA, Jull JW. Human and experimental breast cancer.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Springfield, IL: Charles C. Thomas 1961.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Turner-Warwick RT. The lymphatics of the breast. Br J Surg 1959;46:574.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Sappey MPC. Injection preparation et conservation des vasseaux lym- phatiques. These pour le doctorat en medicine, no 241. Paris: Rignoux Imprimeur de la Faculte de Medecine 1834.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Hultborn KA, Larsen LG, Raghnult I. The lymph drainage from the breast to the axillary and parasternal lymph nodes: studied with the aid of col- loidal Au198. Acta Radiol 1955;43:52.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Lineham DC, Hill ADK, Akhurst T, et al. Intradermal radiocolloid and intra- parenchymal blue dye injection optimize sentinel node identification in breast cancer patients. Ann Surg Oncol 1999;6:450.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Tanis PJ, Nieweg OE, Olmos RAV, et al. Anatomy and physiology of lym- phatic drainage of the breast from the perspective of sentinel node biopsy. J Am Coll Surg 2001;192:399.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Nathanson SD, Nachna DL, Gilman D, et al. Pathways of lymphatic drain- age from the breast. Ann Surg Oncol 2001;8:837.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Cody HS, Fey JV, Akhurst T, et al. Complementarity of blue dye and isotope in sentinel node localization for breast cancer: univariate and multivariate analysis of 966 procedures. Ann Surg Oncol 2001;8:13.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Boolbol SK, Key JV, Borgen PI, et al. Intradermal isotope injection: a highly accurate method of lymphatic mapping in breast carcinoma. Ann Surg Oncol 2001;8:20.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Vargas HI, Tolmos J, Agbunag RV, et al. A validation trial of subdermal injection compared with intraparenchymal injection for sentinel lymph node biopsy in breast cancer. Am Surg 2002;68:87.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Roumen RM, Geuskens LM, Valkenburg JG. In search of the true sentinel node by different injection techniques in breast cancer patients. Eur J Surg Oncol 1999;25:347.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Paganelli G, Galimberti V, Trifiro G, et al. Internal mammary node lympho- scintigraphy and biopsy in breast cancer. Q J Nucl Med 2002;46:138.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Shimazo K, Tamaki Y, Taguchi T, et al. Lymphoscintigraphic visualization of internal mammary node with subtumoral injection of radiocolloid in patients with breast cancer. Ann Surg 2003;237:390.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Feezor RJ, Kasraeian A, Copeland EM III, et al. Sequential dermal-peritu- moral radiocolloid injection for sentinel node biopsy for breast cancer: the University of Florida experience. Am Surg 2002;68:648; discussion 687.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Estourgie SH, Tanis PJ, Nieweg OE, et al. Should the hunt for internal mammary chain sentinel nodes begin? An evaluation of 150 breast cancer patients. Ann Surg Oncol 2003;10:935.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Kern KA. Sentinel lymph node mapping in breast cancer using subareolar injection of blue dye. Eur J Surg Oncol 1999;189:539.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Kern KA, Rosenberg R. Preoperative lymphoscintigraphy during lymphatic mapping for breast cancer: improved sentinel node imaging using subareo- lar injection of technetium-99m sulphur colloid. J Am Coll Surg 2000;191:479.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Klimberg V, Rubio I, Henry R, et al. Subareolar versus peritumoral injec- tion for location of the sentinel lymph nodes. Ann Surg 2001;229:860.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Kern KA. Lymphoscintigraphic anatomy of sentinel lymphatic channels after subareolar injection of technetium 99m sulphur colloid. J Am Coll Surg 2001;193:601.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Suami H, Wei-Ren P, Mann GB, et al. The lymphatic anatomy of the breast and its implications for sentinel lymph node biopsy: a human cadaver study. Ann Surg Oncol 2008;15:863.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Pickren JW. Lymph node metastases in carcinoma of the female mammary gland. Bull Roswell Park Mem Inst 1956;1:79.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Grossman F. Ueber die axillaren lymphdrusen. Dissert. Berlin 1896.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Rotter J. Zur topographic des mammacarcinoms. Arch F Klin Chir 1899; 58:346.
Breast Anatomy and Development	PHYSIOLOGY	Menopause	null	Egan RL, McSweeney MB. Intramammary lymph nodes. Cancer 1983;51:1838.

Breast Anatomy and Development

MORPHOLOGY

Microanatomy of Breast Development

null

Lobules develop during the first few years after men- arche. The alveolar buds cluster around a terminal duct and form type I (virginal) lobules, comprising approximately 11 alveolar buds lined by two layers of epithelium. Full differ- entiation of the mammary gland proceeds through puberty, takes many years, and may not be fully completed if inter- rupted by pregnancies.

Breast Anatomy and Development

MORPHOLOGY

Microanatomy of Breast Development

null

Detailed microanatomic studies of the breast have shown the presence of three distinct types of lobules (55). Type I lobules, previously described, are the first genera- tion of lobules that develop just after the menarche. The transition to type II and type III gradually results from con- tinued sprouting of new alveolar buds. The characteristics of the four lobular types are described in Tables 1-3 and 1-4.

Breast Anatomy and Development

MORPHOLOGY

Microanatomy of Breast Development

null

Russo et al. (56) recently determined that the breast tissue of women with invasive cancer and those with a famil- ial pattern of breast cancer have an architectural pattern dif- ferent from the control group of normal tissue. They also found that the BRCA1 or related genes may have a functional role in the branching pattern of the breast during lobular development. This is seen mainly in the epithelial stroma interaction.

Breast Anatomy and Development

MORPHOLOGY

Microscopic Anatomy of the Adult Breast

null

In the immature breast, the ducts and alveoli are lined by a two-layer epithelium that consists of a basal cuboidal layer and a flattened surface layer. In the presence of estrogens at puberty and subsequently, this epithelium proliferates, becoming multilayered in the adult breast (Figs. 1-5 and 1-6). Three alveolar cell types have been observed: superficial (luminal) A cells, basal B cells (chief cells), and myoepithe- lial cells.

Breast Anatomy and Development

MORPHOLOGY

Microscopic Anatomy of the Adult Breast

null

Superficial, or luminal, A cells are dark, basophilic- staining cells that are rich in ribosomes. Superficial cells undergo intercellular dehiscence, with swelling of the mitochondria, and become grouped, forming buds within the lumen. Basal B cells, or chief cells, are the major cell type in mammary epithelium. They are clear, with an ovoid nucleus without nucleoli. Where the basal cells are in con- tact with the lumen, microvilli occur on the cell membrane. Intracytoplasmic filaments are similar to those in myoepi- thelial cells, suggesting their differentiation toward that cell type. Myoepithelial cells are located around alveoli and small excretory milk ducts between the inner aspect of the basement membrane and the tunica propria. Myoepithelial cells are arranged in a branching, star-like fashion. The sar- coplasm contains filaments that are 50 to 80 nm in diam- eter; these myofilaments are inserted by hemidesmosomes into the basal membrane. These cells are not innervated but are stimulated by the steroid hormones prolactin and oxytocin.

Breast Anatomy and Development

MORPHOLOGY

Anatomy of the Nipple and Breast Ducts

null

Recent advances exploring ductal lavage (57) and direct visualization of the ducts with breast endoscopy (58) have made the anatomy of the nipple clinically relevant. Utilizing six different approaches to examine the duc- tal anatomy, Love and Barsky (59) found that more than 90% of all nipples examined contained five to nine duc- tal orifices, generally arranged as a central group and a peripheral group. The central ducts did not extend in a radial fashion from the nipple as previously thought but traveled back from the nipple toward the chest wall. They also found that each nipple orifice communicated with a

Breast Anatomy and Development

MORPHOLOGY

Anatomy of the Nipple and Breast Ducts

null

separate, nonanastomosing ductal system, which extended to the terminal duct lobular unit. Rusby et al. (60) prospec- tively examined nipples from mastectomy specimens. The median number of ducts was 23, but they found far fewer ductal orifices on the nipple surface. This study demon- strates that many ducts share a few common openings on the nipple surface and explains the discrepancy between the number of ductal openings on the nipple and the num- ber of actual ducts.

Breast Anatomy and Development

MORPHOLOGY

Anatomy of the Nipple and Breast Ducts

null

There is evidence to suggest that both ductal and lobu- lar carcinoma arises in the terminal duct lobular unit. Stolier and Wang (61) examined 32 nipples of mastectomy speci- mens. In 29 of the specimens, there were no terminal duct lobular units identified. Three of the 32 specimens were found to have terminal duct lobular units. All terminal duct lobular units were found at the base of the nipple as opposed to near the tip. As interest in intraductal approaches and treatment increases, so too will knowledge of ductal and nipple anatomy.

Breast Anatomy and Development

MORPHOLOGY

Anatomy of the Nipple and Breast Ducts

null

FIGURE 1-5 Normal lobule in adult female breast. The lobule is the functional unit of the breast. It is lined by two cell layers: inner epithelial layer and outer myoepithelial layer. The latter are inconspicuous on routine hematoxylin and eosin (H&E) stain such as this. (Photomicrograph cour- tesy of Dr. Syed Hoda.)

Breast Anatomy and Development

MORPHOLOGY

Anatomy of the Nipple and Breast Ducts

null

FIGURE 1-6 Normal lobule in adult female breast. p63 immunostain highlights the nuclei of the outer myoepithe- lial cell layer of the lobule. (Photomicrograph courtesy of Dr. Syed Hoda.)

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

Histologic changes in the normal breast have been identified in relation to the endocrine variations of the menstrual cycle

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

(62). Normal menstrual cycle–dependent histologic changes in both stroma and epithelium have been observed.

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

Cyclic changes in the sex steroid hormone levels during the menstrual cycle profoundly influence breast morphol- ogy. Under the influence of follicle-stimulating hormone and luteinizing hormone during the follicular phase of the men- strual cycle, increasing levels of estrogen secreted by the ovarian graafian follicles stimulate breast epithelial prolifera- tion. During this proliferative phase, the epithelium exhibits sprouting, with increased cellular mitoses, RNA synthesis, increased nuclear density, enlargement of the nucleolus, and changes in other intercellular organelles. In particular, the Golgi apparatus, ribosomes, and mitochondria increase in size or number. During the follicular phase, at the time of maximal estrogen synthesis and secretion in midcycle, ovu- lation occurs. A second peak occurs in the midluteal phase, when luteal progesterone synthesis is maximal. Similarly, progestogens induce changes in the mammary epithelium during the luteal phase of the ovulatory cycles. Mammary ducts dilate, and the alveolar epithelial cells differentiate into secretory cells, with a partly monolayer arrangement. The combination of these sex steroid hormones and other hormones results in the formation of lipid droplets in the alveolar cells and some intraluminal secretion.

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

The changes in breast epithelium in response to hor- mones are mediated through either intracellular steroid receptors or membrane-bound peptide receptors. The pres- ence of steroid receptors for estrogen and progestogens in the cytosol of normal mammary epithelium has been demon- strated (63). Through the binding of these hormones to spe- cific receptors, the molecular changes, with their observed morphologic effects, are induced as physiologic changes. Similarly, membrane receptors are present to mediate the actions of prolactin. Increases in endogenous estrogen can also exert a histamine-like effect on the mammary microcir- culation (64), resulting in an increased blood flow 3 to 4 days

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

before menstruation, with an average increase in breast volume of 15 to 30 cm3. Premenstrual breast fullness is attributable to increasing interlobular edema and enhanced ductular–acinar proliferation under the influence of estro- gens and progestogens. With the onset of menstruation, after a rapid decline in the circulating levels of sex steroid hormones, secretory activity of the epithelium regresses.

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

Postmenstrually, tissue edema is reduced, and regres- sion of the epithelium ceases as a new cycle begins, with concomitant rises in estrogen levels. Minimum breast vol- ume is observed 5 to 7 days after menstruation. The cyclic changes in breast cellular growth rates are related to hor- monal variations in the follicular and luteal phases of the menstrual cycle. Measurement of these changes can be made by observation and measurement of a variety of cel- lular and nuclear parameters:

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

Histologic pattern

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

Cellular morphology

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

Nuclear morphology

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

Mitoses

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

Tritiated thymidine uptake

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

Image cytometry

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

Nuclear area

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

Circumference

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

Boundary fluctuation

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

Chromatin granularity

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

Stain intensity

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

Proliferation markers

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

Ki-67

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

Proliferating cell nuclear antigen

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

MIB1

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

Most observations have been made from surgical speci- mens, which are usually from women with breast abnor- malities, or from autopsy specimens, which may have resulted in inconsistent and contradictory results.

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

Most studies have shown that breast epithelial cell pro- liferation increases in the second half (luteal phase) of the menstrual cycle (65–71).

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

A study of nuclear tritiated thymidine uptake in surgi- cally excised breast tissue showed that peak uptake was during the luteal phase on days 22 to 24, coinciding with an increase in circulatory progesterone levels and a second peak of estrogen. The role of estrogen was considered unim- portant because the preovulatory peak of estrogen was not associated with an increase in tritiated thymidine uptake

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

(67). The possibility of a synergistic action between estro- gen and progesterone would therefore be unlikely.

Breast Anatomy and Development

PHYSIOLOGY

Microscopy, Morphology, and the Menstrual Cycle

null

The role of estrogen and progesterone was subsequently studied in explants of human breast tissue implanted sub- cutaneously in nude mice (72). An increase in epithelial cell growth was observed 7 days after exposure to estrogen; pro- gesterone had no effect, and a combination of estrogen and progesterone neither enhanced nor diminished the prolifera- tive effect of estrogen. These observations may explain why proliferation increases during the luteal phase subsequent to the preovulatory estrogen peak.

Breast Anatomy and Development

PHYSIOLOGY

Breast Changes during Pregnancy

null

During pregnancy, marked ductular, lobular, and alveolar growth occurs as a result of the influence of luteal and placental sex steroids, placental lactogen, prolactin, and chorionic gonadotropin (Fig. 1-4B). In experimental studies, these effects are observed when estrogen and progesterone cause a release of prolactin by reducing the hypothalamic release of prolactin-inhibiting factor (PIF) (69). Prolactin in humans is also released progressively during pregnancy and probably stimulates epithelial growth and secretion

Breast Anatomy and Development

PHYSIOLOGY

Breast Changes during Pregnancy

null

(70,71). Prolactin increases slowly during the first half of pregnancy; during the second and third trimesters, blood levels of prolactin are three to five times higher than nor- mal, and mammary epithelium initiates protein synthesis.

Breast Anatomy and Development

PHYSIOLOGY

Breast Changes during Pregnancy

null

In the first 3 to 4 weeks of pregnancy, marked ductular sprouting occurs with some branching, and lobular formation occurs under estrogenic influence. At 5 to 8 weeks, breast enlargement is significant, with dilatation of the superficial veins, heaviness, and increasing pigmentation of the nipple– areolar complex. In the second trimester, lobular formation exceeds ductular sprouting under progestogenic influence. The alveoli contain colostrum but no fat, which is secreted under the influence of prolactin. From the second half of preg- nancy onward, increasing breast size results not from mam- mary epithelial proliferation but from increasing dilatation of the alveoli with colostrum, as well as from hypertrophy of myoepithelial cells, connective tissue, and fat. If these pro- cesses are interrupted by early delivery, lactation may be adequate from 16 weeks of pregnancy onward.

Breast Anatomy and Development

PHYSIOLOGY

Breast Changes during Pregnancy

null

At the beginning of the second trimester, the mammary alveoli, but not the milk ducts, lose the superficial layer of A cells. Before this, as in the nonpregnant woman, the two- layer structure is maintained. In the second and third trimes- ters, this monolayer differentiates into a colostrum–cell layer and accumulates eosinophilic cells, plasma cells, and leuko- cytes around the alveoli. As pregnancy continues, colostrum, composed of desquamated epithelial cells, accumulates. Aggregations of lymphocytes, round cells, and desquamated phagocytic alveolar cells (foam cells) may be found in colos- trum; these are termed the Donné corpuscles.

Breast Anatomy and Development

PHYSIOLOGY

Lactation

null

After parturition, an immediate withdrawal of placental lac- togen and sex steroid hormones occurs. During pregnancy, these hormones antagonize the effect of prolactin on mam- mary epithelium. Concomitant to the abrupt removal of the placental hormones, luteal production of the sex steroid hor- mones also ceases. A nadir is reached on the fourth to fifth day postpartum; at this time, the secretion of PIF from the hypothalamus into the hypothalamoadenohypophyseal por- tal system decreases. This reduction in PIF secretion allows the transmembrane secretion of prolactin by pituitary lacto- trophs. Sex steroid hormones are not necessary for successful lactation, and physiologic increases, such as may occur with postpartum ovulatory cycles, do not inhibit it.

Breast Anatomy and Development

PHYSIOLOGY

Lactation

null

Prolactin, in the presence of growth hormone, insulin, and cortisol, converts the mammary epithelial cells from a presecretory to a secretory state. During the first 4 or 5 days after giving birth, the breasts enlarge as a result of the accu- mulation of secretions in the alveoli and ducts (Fig. 1-7). The initial secretion is of colostrum, a thin, serous fluid that is, at first, sticky and yellow. Colostrum contains lactoglobulin, which is identical to blood immunoglobulins. The importance of these immunoglobulins is unknown; many maternal anti- bodies cross the placenta, transferring passive immunity to the fetus in utero. Fatty acids such as decadienoic acid, phos- pholipids, fat-soluble vitamins, and lactalbumin in colostrum have considerable nutritional value. After colostrum secre- tion, transitional milk and then mature milk are elaborated.

Breast Anatomy and Development

PHYSIOLOGY

Lactation

Mechanisms of Milk Synthesis and Secretion

The effects of prolactin are mediated through membrane receptors in the mammary epithelial cells. The release of prolactin is maintained and stimulated by suckling, as is the release of corticotrophin (adrenocorticotropic hormone). The mammary cells are cuboidal, depending on the degree of intracellular accumulation of secretions. The DNA and RNA of the nuclei increase, and abundant mitochondria,

Breast Anatomy and Development

PHYSIOLOGY

Lactation

Mechanisms of Milk Synthesis and Secretion

FIGURE 1-7 Lactating breast tissue. The glands within the lobules are enlarged and dilated. The stroma within the lobule is diminished. Secretory vacuoles are present within

Breast Anatomy and Development

PHYSIOLOGY

Lactation

Mechanisms of Milk Synthesis and Secretion

the individual lobular epithelial cells. Hematoxylin and eosin (H&E) stain. (Photomicrograph courtesy of Dr. Syed Hoda.)

Breast Anatomy and Development

PHYSIOLOGY

Lactation

Mechanisms of Milk Synthesis and Secretion

ribosomes, and rough endoplasmic reticulum, with a promi- nent Golgi apparatus, are apparent in the epithelial cells. Complex protein, mild fat, and lactose synthetic pathways are activated, as are water–ion transport mechanisms. These processes are initiated by the activation of hormone-specific membrane receptors. Changes in cyclic adenosine mono- phosphate stimulate milk synthesis through the induction of messenger and transfer RNA. Prolactin stimulates cyclic adenosine monophosphate–induced protein kinase activity, resulting in the phosphorylation of milk proteins. Polymerase activity and cellular transcription are enhanced (17).

Breast Anatomy and Development

PHYSIOLOGY

Lactation

Mechanisms of Milk Synthesis and Secretion

Large fat vacuoles develop and move toward the apex of the cell. At the same time, the nucleus also moves toward the apex. As the water intake of the cell increases, longitudinal cellular striations may be observed. Ultimately, the vacuoles pass from the cell along with part of the cell membrane and cytoplasm; the apical cell membrane reconstitutes as secretion takes place.

Breast Anatomy and Development

PHYSIOLOGY

Lactation

Mechanisms of Milk Synthesis and Secretion

FIGURE 1-8 Atrophic breast tissue in a postmenopausal woman. Only a few atrophic ducts and lobules are present amid dense fibrous and fatty tissue. Hematoxylin and eosin (H&E) stain. (Photomicrograph courtesy of Dr. Syed Hoda.)

Breast Anatomy and Development

PHYSIOLOGY

Lactation

Mechanisms of Milk Synthesis and Secretion

Enhanced activity occurs during suckling. Fat is secreted chiefly through an apocrine mechanism, lactose is secreted through a merocrine mechanism, and the secretion of pro- teins occurs as a result of a combination of mechanisms. Ions enter the milk by diffusion and active transport. Relatively little holocrine secretion is thought to take place. The end result of secretion and subsequent intraductal dilution of extracellular fluid is milk, comprising a suspension of pro- teins—casein, -lactalbumin, and -lactoglobulin—and fat in a lactose–mineral solution. The white appearance of milk is due to emulsified lipids and calcium caseinate, whereas the yel- low color of butterfat is due to the presence of carotenoids.

Breast Anatomy and Development

PHYSIOLOGY

Lactation

Mechanisms of Milk Ejection

The removal of milk by suckling is aided by active ejection. Sensory nerve endings in the nipple–areolar complex are activated by tactile stimuli. Impulses pass by way of sensory nerves through the dorsal roots to the spinal cord. In the spinal cord, impulses are relayed through the dorsal, lateral, and ventral spinothalamic tracts to the mesencephalon and lateral hypothalamus. Inhibition of PIF secretion permits the unimpeded secretion of prolactin from the anterior pitu- itary. Simultaneously, through a different pathway in the paraventricular nucleus, the synthesis of oxytocin occurs. Oxytocin is released from the posterior pituitary neu- rovesicles by impulses traveling along the neurosecretory fibers of the hypothalamoneurohypophyseal tract. Oxytocin released into the systemic circulation acts on the myoepi- thelial cells, which contract and eject milk from the alveoli into the lactiferous ducts and sinuses. This phenomenon is specific to oxytocin, and changes in intramammary ductal pressures of 20 to 25 mm Hg may be observed in relation to peak blood levels. Oxytocin also acts on the uterus and cervix to promote involution. This effect may be stimulated by cervical dilatation and by vaginal stretching through the ascending afferent neural pathways (Ferguson reflex).

Breast Anatomy and Development

PHYSIOLOGY

Lactation

Mechanisms of Milk Ejection

Complex neuroendocrine interactions determine normal lactation. An appreciation of these mechanisms is essential to the understanding of abnormalities and to the treatment of problems of lactation (17).

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Menopause is the result of the atresia of more than 400,000 follicles that are present in the ovaries of a female fetus at 5 months’ gestation. Declining ovarian function in late pre- menopause through the menopause leads to regression of epithelial structures and stroma. Menopausal involution of the breast results in reduction of both the number of ducts and lobules. Stromal changes dominate and fat deposition increases while the regression of connective tissue continues. The duct system remains, but the lobules shrink and collapse (Fig. 1-8). Lymphatic channels are also reduced in number in the postmenopausal breast (36). The last structures to appear with sexual maturity are the first ones to regress (17).

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

REFERENCES

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Hamilton NJ, Boyd JD, Mossman HW. Human embryology. Cambridge: Heffer 1968:428.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Cardiff RD, Wellings SR. The comparative pathology of human and mouse mammary glands. J Mammary Gland Biol Neoplasia 1999;4:105.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Hughes ESR. Development of the mammary gland. Ann R Coll Surg Engl

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

1950;6:99.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Dawson EK. A histological study of the normal mamma in relation to tumour growth: I. Early development to maturity. Edinb Med J 1934;41:653.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Moffat DF, Going JJ. Three dimensional anatomy of complete duct sys- tems in human breast: pathological and developmental implications. J Clin Pathol 1996;49:48.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Mimoumi R, Merlob P, Reisner SH. Occurrence of supernumerary nipples in newborns. Am J Dis Children 1983;137:952.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Urbani CE, Betti R. Accessory mammary tissue associated with congenital and hereditary nephrourinary malformations. Int J Dermatol 1996;35:349.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Grotto I, Browner-Elhanan K, Mimouni D, et al. Occurrence of supernu- merary nipples in children with kidney and urinary tract malformations. Pediatr Dermatol 2001;40:637.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Jojart G, Seres E. Supernumerary nipple and renal anomalies. Int Urol Nephrol 1994;26:141.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Maliniac JW. Breast deformities and their origin. New York: Grune & Stratton 1950:163.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Simon BE, Hoffman S, Kahn S. Treatment of asymmetry of the breasts. Clin Plast Surg 1975;2:375.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Trier WC. Complete breast absence. Plast Reconstr Surg 1965;36:430.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Pers M. Aplasias of the anterior thoracic wall, the pectoral muscle, and the breast. Scand J Plast Reconstr Surg 1968;2:125.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Beals RK, Crawford S. Congenital absence of the pectoral muscles. Clin Orthop 1976;119:166.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

McDowell F. On the propagation, perpetuation and parroting of erroneous eponyms such as “Poland’s syndrome.” Plast Reconstr Surg 1977;59:561.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Ravitch MM. Poland’s syndrome: a study of an eponym. Plast Reconstr Surg

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

1977;59:508.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Vorherr H. The breast: morphology, physiology and lactation. New York: Academic Press 1974.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Tanner JM. Wachstun und Reifung des Menschen. Stuttgart: Georg Thieme Verlag 1962.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Parks AG. The micro-anatomy of the breast. Ann R Coll Surg Engl 1959;25:235.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Spratt JS. Anatomy of the breast. Major Probl Clin Surg 1979;5:1.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Bonsor GM, Dossett JA, Jull JW. Human and experimental breast cancer.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Springfield, IL: Charles C. Thomas 1961.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Turner-Warwick RT. The lymphatics of the breast. Br J Surg 1959;46:574.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Sappey MPC. Injection preparation et conservation des vasseaux lym- phatiques. These pour le doctorat en medicine, no 241. Paris: Rignoux Imprimeur de la Faculte de Medecine 1834.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Hultborn KA, Larsen LG, Raghnult I. The lymph drainage from the breast to the axillary and parasternal lymph nodes: studied with the aid of col- loidal Au198. Acta Radiol 1955;43:52.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Lineham DC, Hill ADK, Akhurst T, et al. Intradermal radiocolloid and intra- parenchymal blue dye injection optimize sentinel node identification in breast cancer patients. Ann Surg Oncol 1999;6:450.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Tanis PJ, Nieweg OE, Olmos RAV, et al. Anatomy and physiology of lym- phatic drainage of the breast from the perspective of sentinel node biopsy. J Am Coll Surg 2001;192:399.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Nathanson SD, Nachna DL, Gilman D, et al. Pathways of lymphatic drain- age from the breast. Ann Surg Oncol 2001;8:837.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Cody HS, Fey JV, Akhurst T, et al. Complementarity of blue dye and isotope in sentinel node localization for breast cancer: univariate and multivariate analysis of 966 procedures. Ann Surg Oncol 2001;8:13.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Boolbol SK, Key JV, Borgen PI, et al. Intradermal isotope injection: a highly accurate method of lymphatic mapping in breast carcinoma. Ann Surg Oncol 2001;8:20.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Vargas HI, Tolmos J, Agbunag RV, et al. A validation trial of subdermal injection compared with intraparenchymal injection for sentinel lymph node biopsy in breast cancer. Am Surg 2002;68:87.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Roumen RM, Geuskens LM, Valkenburg JG. In search of the true sentinel node by different injection techniques in breast cancer patients. Eur J Surg Oncol 1999;25:347.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Paganelli G, Galimberti V, Trifiro G, et al. Internal mammary node lympho- scintigraphy and biopsy in breast cancer. Q J Nucl Med 2002;46:138.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Shimazo K, Tamaki Y, Taguchi T, et al. Lymphoscintigraphic visualization of internal mammary node with subtumoral injection of radiocolloid in patients with breast cancer. Ann Surg 2003;237:390.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Feezor RJ, Kasraeian A, Copeland EM III, et al. Sequential dermal-peritu- moral radiocolloid injection for sentinel node biopsy for breast cancer: the University of Florida experience. Am Surg 2002;68:648; discussion 687.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Estourgie SH, Tanis PJ, Nieweg OE, et al. Should the hunt for internal mammary chain sentinel nodes begin? An evaluation of 150 breast cancer patients. Ann Surg Oncol 2003;10:935.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Kern KA. Sentinel lymph node mapping in breast cancer using subareolar injection of blue dye. Eur J Surg Oncol 1999;189:539.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Kern KA, Rosenberg R. Preoperative lymphoscintigraphy during lymphatic mapping for breast cancer: improved sentinel node imaging using subareo- lar injection of technetium-99m sulphur colloid. J Am Coll Surg 2000;191:479.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Klimberg V, Rubio I, Henry R, et al. Subareolar versus peritumoral injec- tion for location of the sentinel lymph nodes. Ann Surg 2001;229:860.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Kern KA. Lymphoscintigraphic anatomy of sentinel lymphatic channels after subareolar injection of technetium 99m sulphur colloid. J Am Coll Surg 2001;193:601.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Suami H, Wei-Ren P, Mann GB, et al. The lymphatic anatomy of the breast and its implications for sentinel lymph node biopsy: a human cadaver study. Ann Surg Oncol 2008;15:863.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Pickren JW. Lymph node metastases in carcinoma of the female mammary gland. Bull Roswell Park Mem Inst 1956;1:79.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Grossman F. Ueber die axillaren lymphdrusen. Dissert. Berlin 1896.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

null

Rotter J. Zur topographic des mammacarcinoms. Arch F Klin Chir 1899; 58:346.

Breast Anatomy and Development

PHYSIOLOGY

Menopause

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Egan RL, McSweeney MB. Intramammary lymph nodes. Cancer 1983;51:1838.