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Inside the Lactating : The Latest Research Donna T. Geddes, PhD

Although it is well recognized that a thorough understanding of the anatomy of an is essential to enable assessment of any abnormalities in that organ, there has been little investigation of the anatomy of the normal lactating breast since Sir Astley Cooper performed detailed dissections of the anatomy of the breast more than 160 years ago. Many mothers recognize that breast provides the ultimate nutrition and protection for the ; however, a significant proportion of women experience difficulties , some of which lead to the infant. Recently, a small number of studies have focused on the gross anatomy of the breast, and have found that the ductal system is comprised of fewer numbers of main ducts than previously thought. In addition, the ducts are compressible and do not contain large amounts of milk, the amount of fatty tissue in the breast is variable, and a proportion is situated within the glandular tissue. These findings add to our understanding of both the physiology and pathology of the lactating breast. J Midwifery Womens Health 2007;52:556–563 © 2007 by the American College of Nurse-Midwives. keywords: anatomy, breast, breastfeeding, ,

INTRODUCTION The breast reaches its full functional capacity Fetal Development during lactation with the production of . In The human breast develops from a thickened ectodermal order to diagnose and treat breastfeeding problems and ridge (milk line) situated longitudinally along the ante- pathologies that arise during lactation, it is essential to rior body wall from the groin to the axilla at about 6 have an extensive understanding of the normal anatomy weeks’ gestation. Regression of the ridge occurs except and physiology of the breast. This review details the for the pectoral region (2nd–6th rib), which forms the development of the breast and the most recent findings in mammary gland. Supernumerary glands may develop breast anatomy. The effect breast anatomy has upon anywhere along the ectodermal ridges, and in 2% to 6% clinical practice as well as the importance of milk of women, these glands either mature into mammary ejection is reviewed. glands or remain as accessory .4,5 During the 7th and 8th weeks of gestation, the mam- DEVELOPMENT OF THE BREAST mary parenchyma invades the stroma, which appears as a While it is undisputed that breast milk provides the raised portion called the mammary disc. Between the optimal nutrition for the developing infant, breast milk 10th and 12th weeks, epithelial buds form; parenchymal also contains unique protective factors for the mother.1 It branching occurs during the 13th through 20th weeks. has been hypothesized that the mammary gland first Between the 12th and 16th weeks of gestation, the evolved from the innate as an inflamma- smooth musculature of the and are formed, tory response to provide protection to the young, and that and at approximately 20 weeks’ gestation, between 15 nutritional factors developed later.2,3 To date, nutrition and 256 solid cords form in the . has assumed a position of dominance over the protective Branching continues, and canalization of the cords oc- factors in considerations of the physiology of human curs, forming the primary milk ducts by 32 weeks’ lactation. gestation.6 At 32 weeks’ gestation the ducts open onto the The human breast is a dynamic organ that does not go area, which develops into the nipple.7 The of through all developmental stages unless a woman expe- the mammary gland develops from connective tissue that riences and . The course of breast has lost its capacity to form fibres, and it is considered development can be described in distinct phases begin- necessary to further growth of the parenchyma.4 ning with the fetal phase and progressing through the Shortly after , can be expressed from neonatal/prepubertal and postpubertal phases. Develop- the infant’s mammary glands. This is attributed to the ment of the breast can then proceed through a number of pro-lactation present in the fetal circulation at lactation cycles (pregnancy, lactogenesis I, lactogenesis birth. Regression of the mammary gland usually occurs II, and ; (see review by Kent on page 564). by 4 weeks postpartum and coincides with a decrease in the secretion of from the anterior of the infant.4

Address correspondence to Donna T. Geddes, PhD, Department of Bio- chemistry and Molecular Biology, School of Biomedical, Biomolecular Neonatal and Prepubertal Development and Chemical Sciences, Faculty of Life and Physical Sciences, M310–The University of Western Australia, 35 Stirling Highway, Crawley WA 6009 The ducts in the newborn breast are rudimentary and Australia. E-mail: [email protected] have small, club-like ends that regress soon after birth.

556 Volume 52, No. 6, November/December 2007 © 2007 by the American College of Nurse-Midwives 1526-9523/07/$32.00 • doi:10.1016/j.jmwh.2007.05.004 Issued by Elsevier Inc. Before , the growth of the breast is isometric. Allometric growth of both the stroma and begins with the onset of puberty (8–12 years of age). Although the impact of obesity on breast development at this stage is unknown, it is of interest that fed a diet that is higher than their energy requirements have impaired mammary development and subsequent im- paired lactation performance.8,9

Puberty At puberty, the increase in breast size is mainly caused by the increased deposition of adipose tissue within the gland. However, progressive elongation and branching of the ducts creates a more extensive ductal network.10 The major site of growth is the bud-like structures at the end of the ducts, and these form the terminal lobular units or acini.11 Although knowledge of the hormonal regulation of mammary growth during puberty is not extensive, these maturational changes are associated with increased plasma concentrations of oestrogen, prolactin, Figure 1. Artist’s impression of the ductal system of the human lactating luteinizing , follicle stimulating hormone, and breast. The ductal system was injected with coloured wax and dissected. (Reproduced from Cooper.16) .12,13

Menstrual Cycle Changes Although it is generally thought that each is a single entity, a recent study that created three-dimensional During the of the , the reconstructions of the entire ductal system (16 lobes) of lobules are small, with few alveoli, and there is low a mastectomized breast of a 69-year-old was able mitotic activity. During the , the lobules and to demonstrate two connections between lobes.19 It is alveoli develop with open lumens and mitotic activity is generally believed that 15 to 25 ducts drain the alveoli at its greatest.14 From day 27 to , these and merge into larger ducts that eventually converge into changes regress. However, the degeneration of the epi- one main milk duct which dilates slightly to form the thelial growth is not complete,15 and some of the follic- lactiferous sinus before narrowing as it passes through ular growth remains until the next cycle. With increasing the nipple and opens onto the nipple surface (Figure 2). years, there is a relative decrease in mitotic activity until Recent histologic sections of mastectomy nipples have about 35 years of age, when breast development pla- shown more than 17 ducts on average18,20; however, it is teaus.4 not known whether these are all patent, and others suggest the average number of ducts is lower (5–9).21 GROSS ANATOMY OF THE NON-LACTATING BREAST The diameters of the main ducts in the non-lactating For the past 160 years, the descriptions of the anatomy of breast as measured by ultrasound are between 1.2 mm the breast have changed little since Sir Astley Cooper’s16 and 2.5 mm in diameter. Dilated ducts in the non- meticulous dissections of of women who were lactating breast may be caused by conditions such as lactating when they died (Figure 1). polycystic ovarian disease22 or ductal ectasia. The nipple The breast is composed of glandular (secretory) and pores are 0.4 mm to 0.7 mm in diameter and are adipose (fatty) tissue, and is supported by a loose surrounded by circular muscle fibres.4,5 framework of fibrous connective tissue called Cooper’s The heterogeneous distribution of glandular and adi- ligaments. Traditional descriptions of breast anatomy pose tissue in the breast has hindered measurement of describe the glandular tissue as consisting of 15 to 20 these tissues. However, the ratio of glandular to adipose lobes that are comprised of lobules containing between tissue estimated by mammography is 1:1 on average, and 10 and 100 alveoli that are approximately 0.12 mm in it is well documented that the proportion of glandular diameter17 (Figure 2). The size of each lobe is extremely tissue declines with both advancing age23 and increasing variable, and some lobes may differ by 20-to 30-fold.18 breast size.24

Arterial Supply Donna T. Geddes, PhD, is a research associate in the School of Biomedical, Biomolecular and Chemical Sciences at The University of Western The blood supply to the breast is provided mainly by the Australia. anterior and posterior medial branches of the internal

Journal of Midwifery & Women’s Health • www.jmwh.org 557 Figure 2. A, Traditional schematic diagram of the anatomy of the breast. The main milk ducts below the nipple are depicted as dilated portions or lactiferous sinuses, and the glandular tissue is deeper within the breast. B, Schematic diagram of the ductal anatomy of the breast based on the findings of Ramsay et al.38 Milk ducts are shown to be small and branch a short distance from the base of the nipple. The ductal system is erratic and glandular tissue is situated directly beneath the nipple. (Reproduced with permission from Medela AG.) mammary (60%) and the lateral mammary branch Lymphatic Drainage of the (30%).25 Smaller sources of The drainage of from the breast has been exten- arterial blood include the posterior intercostal sively investigated with particular reference to breast and the pectoral branch of the thoracoacromial artery.5 carcinoma, and there are two main pathways by which There is wide variation in the proportion of blood lymph is drained from the breast. The first is to the supplied by each artery between women,26 and little axillary nodes; the second is to the internal mammary evidence of symmetry between breasts. Moreover, the nodes. The majority of the lymph from both the medial course of the arteries does not appear to be associated and lateral portions of the breast is drained to the axillary with the ductal system of the breast.4 nodes (75%), whereas the internal mammary nodes receive lymph from the deep portion of the breast. Venous Drainage However, as expected, there is a wide variation in the drainage of lymph from the breast, and less common The venous drainage of the breast is divided into the deep pathways have been demonstrated.5 and superficial systems which are joined by short con- necting . Both systems drain into the internal thoracic, axillary, and cephalic veins. The deep veins are PREGNANCY assumed to follow the corresponding mammary arteries, During the first half of pregnancy, extension and branch- while the superficial plexus consists of subareolar veins ing of the ductal system occurs, along with intensified that arise radially from the nipple and drain into the lobular–alveolar growth (mammogenesis). Growth of the periareolar , which circles the nipple and connects mammary gland is influenced by a number of hormones, the superficial and deep plexus. Symmetry of the super- including oestrogen, , prolactin, growth hor- 25 ficial venous plexus is not apparent. mone, epidermal , fibroblast growth factor, -like growth factor,28,29 and parathyroid hormone– related .30 Growth of the glandular tissue is be- Innervation lieved to occur by invasion of the adipose tissue.4 By Cooper16 showed that the 2nd to 6th intercostal mid-pregnancy, there is some secretory development, supply the breast. The distribution and course of these with colostrum present in the alveoli and milk ducts. In nerves are complex and variable. The anterior nerves the last trimester, there is a further increase in lobular take a superficial course in the subcutaneous tissues, size. while the lateral nerves travel a deep course through the While these changes typically lead to a marked in- breast. The nipple and areola are supplied by the anterior crease in breast size during pregnancy, the proportion of and lateral cutaneous branches of the 3rd to 5th intercos- growth varies greatly between women, ranging from tal nerves most commonly the 4th intercostal .27 little or no increase to a considerable increase in size.

558 Volume 52, No. 6, November/December 2007 While the major increase in breast size is usually com- described the milk ducts as being significantly larger pleted by week 22 of pregnancy, significant breast compared to those of the non-lactating breast. In contrast, growth occurs during the last trimester of pregnancy in Cardenosa and Eklund35 have reported that the ducts do some women, and some women undergo significant not enlarge during lactation. breast growth postpartum. At the end of pregnancy, the To date, both computed tomography and magnetic volume of breast tissue had increased by 145 Ϯ 19 ml resonance imaging have had little to offer in elucidating (mean Ϯ standard error of the mean; n ϭ 13; range, mammary anatomy. However, in two recent studies that 12–227 ml), with a further increase to 211 Ϯ 16 ml (n ϭ used magnetic resonance imaging to image the breast, 12; range, 129–320 ml) by 1 month of lactation. The rate one study was able to identify some central ducts in the of growth of the mother’s breast during pregnancy is breasts of lactating women,36 and another attempted to correlated with the increase in the concentration of quantify fatty and glandular tissue volumes in the breasts human in the mother’s blood, which of non-lactating women.37 These findings suggest that suggests that this hormone stimulates breast growth in this modality may offer some new insights into the 31 women. anatomy of the breast in future. During pregnancy, mammary blood flow approxi- Our laboratory has recently reinvestigated the anatomy mately doubles in volume. This increased blood flow is of the lactating breast using high-resolution ultrasound.38 concomitant with both the increased metabolic activity Ultrasound is non-invasive and allows the structures of and temperature of the breast. This elevation in blood the breast to be examined without distortion. Compared flow persists during lactation and appears to decline to 4,5 32 with the quoted 15 to 25 ducts of conventional texts, prepregnancy levels about 2 weeks after weaning. fewer ducts were imaged with ultrasound (mean, 9; range, 4–8), which concurs with both Love and Bar- GROSS ANATOMY OF THE LACTATING BREAST sky’s21 observations of lactating women expressing milk with a breast pump (mean, 5; range, 1–17) and Going and The breast reaches its full functional capacity at lactation, Moffatt’s39 dissection of a nipple (4 patent ducts) from a and as a result, several internal and external changes woman who was lactating. Interestingly, these are in occur. During pregnancy, the areola darkens in colour, agreement with Cooper,16 who found 7 to 12 patent ducts and the Montgomery glands, which are a combination of in cadaver dissections of breast from a woman who was sebaceous glands and mammary milk glands, increase in lactating before , although he could cannulate up to size. The secretions of these glands, which number 22 ducts. between 1 and 15,33 are thought to provide maternal Ultrasound imaging has also elucidated other charac- protection from both the mechanical stress of sucking and pathogenic invasion. In addition, it is also suspected teristics of the milk ducts, in that they are small (mean, 2 the secretion may act as a means of communication with mm), superficial, and easily compressed. In addition, the infant via odor. In this connection, a recent study they do not display the typical sac like appearance of the demonstrated that increased numbers of Montgomery “lactiferous sinus” originally thought to exist (Figure 3). glands is associated with increased infant weight gain in Instead, branches drain glandular tissue located directly beneath the nipple and often merge into the main the first 3 days after birth, infant breastfeeding behaviour 38 (increased latching speed and sucking activity), and collecting duct very close to the nipple (Figure 3). Furthermore, the milk ducts increase in diameter at milk decreased time to onset of lactation in primiparous 40 mothers,33 suggesting that there is indeed a functional ejection, leading to the conclusion that it is likely that role of the Montgomery glands during lactation. the main function of the ducts is the transport rather than The standard descriptions of the human breast are storage of milk. In addition, the actual course of the ducts based on Cooper’s16 magnificent cadaver dissections of from the nipple into the breast is erratic, and they are 38 the breasts of women who were lactating at the time of intertwined much like the roots of a tree (Figure 1), 5 death. Although imaging modalities have become more making them difficult to separate surgically. sophisticated, research has focused extensively on abnor- It is widely believed that the lactating breast is malities of the non-lactating breast. Mammography of predominantly composed of glandular tissue during lac- the lactating breast is limited because of the increase in tation. Using a semi-quantitative ultrasound measure- glandular tissue and the secretion of breast milk, which ment of the glandular and adipose tissues in the breast, causes an increase in radiodensity, making images of the we have found there to be approximately twice as much breast difficult to interpret.34 glandular tissue as adipose tissue in the lactating breast. Galactography (the injection of radio-opaque contrast However, there is great variability, and in some women, media into the duct orifice at the nipple and subsequent up to half of the breast is comprised of adipose tissue. In radiography) has illustrated only a portion of the ductal addition, the amount of fat situated between the glandular system, and few studies have examined lactating women. tissues is highly variable. At this stage, no relationship Of those that have looked at lactating breasts, some have between the amount of glandular tissue in the breast and

Journal of Midwifery & Women’s Health • www.jmwh.org 559 in mothers with very , breast hypoplasia (too little glandular tissue), or hyperplasia (overgrowth of glandular tissue). With rising rates of obesity, there is some concern about the effect of obesity on lactation, particularly with increasing reports that obese women are experiencing breastfeeding difficulties (see review by Jevitt et al. on page 606). Only a few studies have been carried out to investigate the effect of obesity on lacta- tion, and they have been difficult to perform because of known confounding factors such as the mode of delivery and parity. These studies show that pregnant women with a high are more likely to experience delayed lactogenesis II.44 While the cause of delayed lactation is not clear, hormonal influences on milk production, increased difficulty attaining a successful infant latch to the breast, and socio-cultural factors have been suggested.45 Knowledge of the normal features of the ductal system is integral to diagnosing ductal abnormalities such as galactoceles and blocked ducts. A palpable lump and ultrasonic features of non-compressible ducts is indica- tive of a blocked duct and should not be considered “normal” for the lactating breast. Furthermore, the ultra- sound scan may identify the level of the blockage, Figure 3. A and B, Ultrasound image of a main milk duct (Toshiba, Aplio). providing useful information for treatment with thera- The nipple is the round hypoechoic (dark) structure in the left of peutic ultrasound. the image (N). The main duct (M) branches into two ducts Mothers of premature and sick rely on breast (B) approximately 5 mm from the nipple. Note the small diameter of the ducts (approximately 3 mm). pumps to initiate and maintain lactation. Clinically, it has been observed that larger shield sizes may optimize milk removal for some mothers. It is therefore feasible that either the storage capacity of the breast or milk produc- compression of superficial ducts within the breast by the tion has been demonstrated.38 shield may indeed compromise milk flow. Further re- Nerve fibres have been identified in association with search is required to determine the effect of ductal the major duct system in the lactating breast; however, anatomy on pumping performance in women. they are sparse in the region of the smaller ducts, areola, Many women who have surgery may and nipple.41 Although these nerves are sensory, apart be able to partially breastfeed their infant, but relatively from a marked increase in areola and nipple sensitivity few are able to exclusively breastfeed.52 This is likely within the first 24 hours postpartum,42 women tend not to because of the codistribution of glandular and fatty tissue be particularly sensitive to breast changes associated within both the lactating38 and non-lactating breast,53 with some abnormal conditions. For example, women making it difficult to preferentially remove fatty tissue. In with mastitis often experience influenza-like symptoms addition, milk outflow is probably disrupted, because before becoming aware of breast tenderness or the there are fewer numbers of ducts than previously presence of a blocked duct. In addition, the absence of thought.21,38 Furthermore, it is possible that the milk motor innervation of the lactocyte and glandular tissue ejection reflex may be inhibited if the nerve supply to the further supports that the production of milk is indepen- nipple is disturbed. dent of neural stimulation.43 It should be noted, however, The absence of lactiferous sinuses or milk reservoirs that as with the gross anatomy of the breast, the nerve leads one to reconsider the mechanism by which the supply of the breast has not been extensively investigated infant removes milk from the breast. Generally, it is recently. believed that the predominant action involved in remov- These new findings with regard to breast anatomy ing milk from the breast is peristalsis or a stripping have several clinical implications (Table 1). For exam- action.54 We have found that milk flows into the infant’s ple, abnormalities of the lactating breast have not been mouth when its tongue is lowered and vacuum is applied extensively investigated in comparison to the pathologi- to the breast. This finding suggests that the vacuum cal, non-lactating breast. Although ultrasound imaging is applied by the breastfeeding infant is a major component only semi-quantitative and can be subjective, it may of milk removal.55 Indeed, it is evident that correct provide information on the proportion of glandular tissue positioning and attachment of the infant to the breast is

560 Volume 52, No. 6, November/December 2007 Table 1. Summary of Some of the Common Breastfeeding Conditions and Symptoms and the Connection With Breast Anatomy

Clinical Condition Symptoms Anatomical Relationship Glandular anomaly Hypoplasia Low milk production Possible deficiency of glandular tissue Hyperplasia Excessive breast growth, Excess glandular tissue lymphoderma, possible necrosis Breast surgery Reduction Low milk production Large volume of glandular tissue removed, severing milk ducts (fewer in number than mammoplasty previously thought); possible nerve damage inhibiting milk ejection reflex Low milk production Possible compression of milk ducts by implant Possible deficiency in volume of glandular tissue Palpable mass Blocked duct Mass (small or large) Ϯ pain Compression of ducts: possible cause of blocked duct; if large lobe affected a significant Possible reduction in milk reduction in milk production may occur; identification of the level of duct obstruction production by ultrasound ensures treatment of entire affected area Galactocele Mass (generally small) Possible ductal abnormality Benign mass (cyst, Mass Possible compression of ducts causing blocked duct; possible obstruction of milk flow in fibroadenoma) the area of attachment of the infant to the breast Malignant mass Palpable non-resolving mass Irregular shaped mass that may be mistaken for a blocked duct or galactocele; ultrasound Ϯ mammography needed for diagnosis Infant sucking Ineffective suck Lack of milk sinuses and evidence that vacuum plays a major role in milk removal may mechanism alter intervention Milk expression Differences in efficiency of Theorized that women with large milk ducts or duct dilations at milk ejection express pumping milk quickly Differences in effectiveness of Poor shield fit may result in compression of superficial ducts and inhibit milk flow pumping Milk ejection Time of increased milk availability Small ducts lacking lactiferous sinuses do not store a large amount of milk; optimization of milk removal during milk ejection will improve milk removal from the breast important for successful breastfeeding; however, the though many women are able to sense the first milk mechanism should be fully understood in order to diag- ejection, few are able to sense subsequent ones. nose and manage infants with sucking abnormalities. While it is well known that stress can influence milk Finally, the absence of the lactiferous sinuses further ejection—resulting in diminished amounts of milk re- emphasises the critical nature of milk ejection for suc- moved by both the infant48 and breast pump51—it is cessful breastfeeding, because only small amounts of often the subtle stress which affects maternal confidence milk are available before the stimulation of milk ejec- and subsequently milk ejection that is overlooked. There- tion.40,46 fore, it is important to provide positive support to the mother during both breastfeeding and pumping. Another MILK EJECTION factor that may influence milk ejection and milk removal is the ductal anatomy of the breast. In a study of mothers Milk ejection is critical for successful lactation, because expressing with an electric breast pump, ultrasound was only small volumes of milk (1–10 mL) can be either used to image duct dilation in the breast that was not expressed46 or removed by the breastfeeding infant40 pumped. It was found that mothers with larger ducts before milk ejection. Failure to remove sufficient quan- expressed more milk during milk ejection and had longer tities of milk results in a decrease in milk production milk ejections than mothers with smaller ducts.50 There- because of local control mechanisms.47 Stimulation of fore, the rate of milk removal for a mother may be the nipple initiates milk ejection via initiation of nervous influenced in part by her ductal anatomy. impulses to the , which stimulates the gland to release into the CONCLUSION bloodstream.48 Oxytocin causes the myoepithelial cells surrounding the alveoli to contract, forcing milk into the New anatomy research has shown that the milk ducts of ducts. This results in increased intraductal pressure,49 the breast are small, compressible, superficial, and duct dilation40,50 (measured by ultrasound), and conse- closely intertwined. They do not display typical dilated quently increased milk flow rate50 (measured by contin- “sinuses” and do not typically store large amounts of uous weigh balance during breast expression). Multiple milk. In addition, the amount of adipose tissue in the milk ejections almost always occur during breastfeed- breast is highly variable, particularly between the glan- ing40 (mean, 2.5; range, 0–9) and breast expression50 dular tissue. This fundamental knowledge of the anatomy (mean, 3–6 for 15-minute expression period), and al- of the breast—particularly when it is fully functional—

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