Inside the Lactating Breast - Breast `N Baby Lactation Services

Inside the Lactating Breast: The Latest Anatomy Research
Donna T. Geddes, PhD
Although it is well recognized that a thorough understanding of the anatomy of an organ 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 milk provides the ultimate nutrition and protection for the
infant; however, a significant proportion of women experience difficulties breastfeeding, some of which lead
to weaning 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, lactation, mammary gland
INTRODUCTION
BREAST DEVELOPMENT
The human breast reaches its full functional capacity
during lactation with the production of breast milk. In
order to diagnose and treat breastfeeding problems and
pathologies that arise during lactation, it is essential to
have an extensive understanding of the normal anatomy
and physiology of the breast. This review details the
development of the breast and the most recent findings in
breast anatomy. The effect breast anatomy has upon
clinical practice as well as the importance of milk
ejection is reviewed.
Fetal Development
DEVELOPMENT OF THE BREAST
While it is undisputed that breast milk provides the
optimal nutrition for the developing infant, breast milk
also contains unique protective factors for the mother.1 It
has been hypothesized that the mammary gland first
evolved from the innate immune system as an inflammatory response to provide protection to the young, and that
nutritional factors developed later.2,3 To date, nutrition
has assumed a position of dominance over the protective
factors in considerations of the physiology of human
lactation.
The human breast is a dynamic organ that does not go
through all developmental stages unless a woman experiences pregnancy and childbirth. The course of breast
development can be described in distinct phases beginning with the fetal phase and progressing through the
neonatal/prepubertal and postpubertal phases. Development of the breast can then proceed through a number of
lactation cycles (pregnancy, lactogenesis I, lactogenesis
II, and involution; (see review by Kent on page 564).
Address correspondence to Donna T. Geddes, PhD, Department of Biochemistry and Molecular Biology, School of Biomedical, Biomolecular
and Chemical Sciences, Faculty of Life and Physical Sciences, M310 –The
University of Western Australia, 35 Stirling Highway, Crawley WA 6009
Australia. E-mail: [email protected]
556
© 2007 by the American College of Nurse-Midwives
Issued by Elsevier Inc.
The human breast develops from a thickened ectodermal
ridge (milk line) situated longitudinally along the anterior body wall from the groin to the axilla at about 6
weeks’ gestation. Regression of the ridge occurs except
for the pectoral region (2nd– 6th rib), which forms the
mammary gland. Supernumerary glands may develop
anywhere along the ectodermal ridges, and in 2% to 6%
of women, these glands either mature into mammary
glands or remain as accessory nipples.4,5
During the 7th and 8th weeks of gestation, the mammary parenchyma invades the stroma, which appears as a
raised portion called the mammary disc. Between the
10th and 12th weeks, epithelial buds form; parenchymal
branching occurs during the 13th through 20th weeks.
Between the 12th and 16th weeks of gestation, the
smooth musculature of the areola and nipple are formed,
and at approximately 20 weeks’ gestation, between 15
and 256 solid cords form in the subcutaneous tissue.
Branching continues, and canalization of the cords occurs, forming the primary milk ducts by 32 weeks’
gestation.6 At 32 weeks’ gestation the ducts open onto the
area, which develops into the nipple.7 The adipose tissue of
the mammary gland develops from connective tissue that
has lost its capacity to form fibres, and it is considered
necessary to further growth of the parenchyma.4
Shortly after birth, colostrum can be expressed from
the infant’s mammary glands. This is attributed to the
pro-lactation hormones present in the fetal circulation at
birth. Regression of the mammary gland usually occurs
by 4 weeks postpartum and coincides with a decrease in
the secretion of prolactin from the anterior pituitary
gland of the infant.4
Neonatal and Prepubertal Development
The ducts in the newborn breast are rudimentary and
have small, club-like ends that regress soon after birth.
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Before puberty, the growth of the breast is isometric.
Allometric growth of both the stroma and epithelium
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 ruminants fed
a diet that is higher than their energy requirements have
impaired mammary development and subsequent impaired 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 duct 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,
luteinizing hormone, follicle stimulating hormone, and
growth hormone.12,13
Menstrual Cycle Changes
During the follicular phase of the menstrual cycle, the
lobules are small, with few alveoli, and there is low
mitotic activity. During the luteal phase, the lobules and
alveoli develop with open lumens and mitotic activity is
at its greatest.14 From day 27 to menstruation, these
changes regress. However, the degeneration of the epithelial growth is not complete,15 and some of the follicular growth remains until the next cycle. With increasing
years, there is a relative decrease in mitotic activity until
about 35 years of age, when breast development plateaus.4
GROSS ANATOMY OF THE NON-LACTATING BREAST
For the past 160 years, the descriptions of the anatomy of
the breast have changed little since Sir Astley Cooper’s16
meticulous dissections of breasts of women who were
lactating when they died (Figure 1).
The breast is composed of glandular (secretory) and
adipose (fatty) tissue, and is supported by a loose
framework of fibrous connective tissue called Cooper’s
ligaments. Traditional descriptions of breast anatomy
describe the glandular tissue as consisting of 15 to 20
lobes that are comprised of lobules containing between
10 and 100 alveoli that are approximately 0.12 mm in
diameter17 (Figure 2). The size of each lobe is extremely
variable, and some lobes may differ by 20-to 30-fold.18
Figure 1. Artist’s impression of the ductal system of the human lactating
breast. The ductal system was injected with coloured wax and
dissected. (Reproduced from Cooper.16)
Although it is generally thought that each lobe is a single
entity, a recent study that created three-dimensional
reconstructions of the entire ductal system (16 lobes) of
a mastectomized breast of a 69-year-old female was able
to demonstrate two connections between lobes.19 It is
generally believed that 15 to 25 ducts drain the alveoli
and merge into larger ducts that eventually converge into
one main milk duct which dilates slightly to form the
lactiferous sinus before narrowing as it passes through
the nipple and opens onto the nipple surface (Figure 2).
Recent histologic sections of mastectomy nipples have
shown more than 17 ducts on average18,20; however, it is
not known whether these are all patent, and others
suggest the average number of ducts is lower (5–9).21
The diameters of the main ducts in the non-lactating
breast as measured by ultrasound are between 1.2 mm
and 2.5 mm in diameter. Dilated ducts in the nonlactating breast may be caused by conditions such as
polycystic ovarian disease22 or ductal ectasia. The nipple
pores are 0.4 mm to 0.7 mm in diameter and are
surrounded by circular muscle fibres.4,5
The heterogeneous distribution of glandular and adipose tissue in the breast has hindered measurement of
these tissues. However, the ratio of glandular to adipose
tissue estimated by mammography is 1:1 on average, and
it is well documented that the proportion of glandular
tissue declines with both advancing age23 and increasing
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
Australia.
Journal of Midwifery & Women’s Health • www.jmwh.org
The blood supply to the breast is provided mainly by the
anterior and posterior medial branches of the internal
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 artery (60%) and the lateral mammary branch
of the lateral thoracic artery (30%).25 Smaller sources of
arterial blood include the posterior intercostal arteries
and the pectoral branch of the thoracoacromial artery.5
There is wide variation in the proportion of blood
supplied by each artery between women,26 and little
evidence of symmetry between breasts. Moreover, the
course of the arteries does not appear to be associated
with the ductal system of the breast.4
Venous Drainage
The venous drainage of the breast is divided into the deep
and superficial systems which are joined by short connecting veins. Both systems drain into the internal
thoracic, axillary, and cephalic veins. The deep veins are
assumed to follow the corresponding mammary arteries,
while the superficial plexus consists of subareolar veins
that arise radially from the nipple and drain into the
periareolar vein, which circles the nipple and connects
the superficial and deep plexus. Symmetry of the superficial venous plexus is not apparent.25
Innervation
Cooper16 showed that the 2nd to 6th intercostal nerves
supply the breast. The distribution and course of these
nerves are complex and variable. The anterior nerves
take a superficial course in the subcutaneous tissues,
while the lateral nerves travel a deep course through the
breast. The nipple and areola are supplied by the anterior
and lateral cutaneous branches of the 3rd to 5th intercostal nerves most commonly the 4th intercostal nerve.27
558
Lymphatic Drainage
The drainage of lymph from the breast has been extensively investigated with particular reference to breast
carcinoma, and there are two main pathways by which
lymph is drained from the breast. The first is to the
axillary nodes; the second is to the internal mammary
nodes. The majority of the lymph from both the medial
and lateral portions of the breast is drained to the axillary
nodes (75%), whereas the internal mammary nodes
receive lymph from the deep portion of the breast.
However, as expected, there is a wide variation in the
drainage of lymph from the breast, and less common
pathways have been demonstrated.5
PREGNANCY
During the first half of pregnancy, extension and branching of the ductal system occurs, along with intensified
lobular–alveolar growth (mammogenesis). Growth of the
mammary gland is influenced by a number of hormones,
including oestrogen, progesterone, prolactin, growth hormone, epidermal growth factor, fibroblast growth factor,
insulin-like growth factor,28,29 and parathyroid hormone–
related protein.30 Growth of the glandular tissue is believed to occur by invasion of the adipose tissue.4 By
mid-pregnancy, there is some secretory development,
with colostrum present in the alveoli and milk ducts. In
the last trimester, there is a further increase in lobular
size.
While these changes typically lead to a marked increase in breast size during pregnancy, the proportion of
growth varies greatly between women, ranging from
little or no increase to a considerable increase in size.
Volume 52, No. 6, November/December 2007
While the major increase in breast size is usually completed by week 22 of pregnancy, significant breast
growth occurs during the last trimester of pregnancy in
some women, and some women undergo significant
breast growth postpartum. At the end of pregnancy, the
volume of breast tissue had increased by 145 ⫾ 19 ml
(mean ⫾ standard error of the mean; n ⫽ 13; range,
12–227 ml), with a further increase to 211 ⫾ 16 ml (n ⫽
12; range, 129 –320 ml) by 1 month of lactation. The rate
of growth of the mother’s breast during pregnancy is
correlated with the increase in the concentration of
human placental lactogen in the mother’s blood, which
suggests that this hormone stimulates breast growth in
women.31
During pregnancy, mammary blood flow approximately doubles in volume. This increased blood flow is
concomitant with both the increased metabolic activity
and temperature of the breast. This elevation in blood
flow persists during lactation and appears to decline to
prepregnancy levels about 2 weeks after weaning.32
GROSS ANATOMY OF THE LACTATING BREAST
The breast reaches its full functional capacity at lactation,
and as a result, several internal and external changes
occur. During pregnancy, the areola darkens in colour,
and the Montgomery glands, which are a combination of
sebaceous glands and mammary milk glands, increase in
size. The secretions of these glands, which number
between 1 and 15,33 are thought to provide maternal
protection from both the mechanical stress of sucking
and pathogenic invasion. In addition, it is also suspected
the secretion may act as a means of communication with
the infant via odor. In this connection, a recent study
demonstrated that increased numbers of Montgomery
glands is associated with increased infant weight gain in
the first 3 days after birth, infant breastfeeding behaviour
(increased latching speed and sucking activity), and
decreased time to onset of lactation in primiparous
mothers,33 suggesting that there is indeed a functional
role of the Montgomery glands during lactation.
The standard descriptions of the human breast are
based on Cooper’s16 magnificent cadaver dissections of
the breasts of women who were lactating at the time of
death. Although imaging modalities have become more
sophisticated, research has focused extensively on abnormalities of the non-lactating breast. Mammography of
the lactating breast is limited because of the increase in
glandular tissue and the secretion of breast milk, which
causes an increase in radiodensity, making images of the
breast difficult to interpret.34
Galactography (the injection of radio-opaque contrast
media into the duct orifice at the nipple and subsequent
radiography) has illustrated only a portion of the ductal
system, and few studies have examined lactating women.
Of those that have looked at lactating breasts, some have
Journal of Midwifery & Women’s Health • www.jmwh.org
described the milk ducts as being significantly larger
compared to those of the non-lactating breast. In contrast,
Cardenosa and Eklund35 have reported that the ducts do
not enlarge during lactation.
To date, both computed tomography and magnetic
resonance imaging have had little to offer in elucidating
mammary anatomy. However, in two recent studies that
used magnetic resonance imaging to image the breast,
one study was able to identify some central ducts in the
breasts of lactating women,36 and another attempted to
quantify fatty and glandular tissue volumes in the breasts
of non-lactating women.37 These findings suggest that
this modality may offer some new insights into the
anatomy of the breast in future.
Our laboratory has recently reinvestigated the anatomy
of the lactating breast using high-resolution ultrasound.38
Ultrasound is non-invasive and allows the structures of
the breast to be examined without distortion. Compared
with the quoted 15 to 25 ducts of conventional texts,4,5
fewer ducts were imaged with ultrasound (mean, 9;
range, 4 – 8), which concurs with both Love and Barsky’s21 observations of lactating women expressing milk
with a breast pump (mean, 5; range, 1–17) and Going and
Moffatt’s39 dissection of a nipple (4 patent ducts) from a
woman who was lactating. Interestingly, these are in
agreement with Cooper,16 who found 7 to 12 patent ducts
in cadaver dissections of breast from a woman who was
lactating before death, although he could cannulate up to
22 ducts.
Ultrasound imaging has also elucidated other characteristics of the milk ducts, in that they are small (mean, 2
mm), superficial, and easily compressed. In addition,
they do not display the typical sac like appearance of the
“lactiferous sinus” originally thought to exist (Figure 3).
Instead, branches drain glandular tissue located directly
beneath the nipple and often merge into the main
collecting duct very close to the nipple38 (Figure 3).
Furthermore, the milk ducts increase in diameter at milk
ejection,40 leading to the conclusion that it is likely that
the main function of the ducts is the transport rather than
storage of milk. In addition, the actual course of the ducts
from the nipple into the breast is erratic, and they are
intertwined much like the roots of a tree38 (Figure 1),
making them difficult to separate surgically.5
It is widely believed that the lactating breast is
predominantly composed of glandular tissue during lactation. Using a semi-quantitative ultrasound measurement of the glandular and adipose tissues in the breast,
we have found there to be approximately twice as much
glandular tissue as adipose tissue in the lactating breast.
However, there is great variability, and in some women,
up to half of the breast is comprised of adipose tissue. In
addition, the amount of fat situated between the glandular
tissues is highly variable. At this stage, no relationship
between the amount of glandular tissue in the breast and
559
Figure 3. A and B, Ultrasound image of a main milk duct (Toshiba, Aplio).
The nipple is the round hypoechoic (dark) structure in the left of
the image (N). The main duct (M) branches into two ducts
(B) approximately 5 mm from the nipple. Note the small
diameter of the ducts (approximately 3 mm).
either the storage capacity of the breast or milk production has been demonstrated.38
Nerve fibres have been identified in association with
the major duct system in the lactating breast; however,
they are sparse in the region of the smaller ducts, areola,
and nipple.41 Although these nerves are sensory, apart
from a marked increase in areola and nipple sensitivity
within the first 24 hours postpartum,42 women tend not to
be particularly sensitive to breast changes associated
with some abnormal conditions. For example, women
with mastitis often experience influenza-like symptoms
before becoming aware of breast tenderness or the
presence of a blocked duct. In addition, the absence of
motor innervation of the lactocyte and glandular tissue
further supports that the production of milk is independent of neural stimulation.43 It should be noted, however,
that as with the gross anatomy of the breast, the nerve
supply of the breast has not been extensively investigated
recently.
These new findings with regard to breast anatomy
have several clinical implications (Table 1). For example, abnormalities of the lactating breast have not been
extensively investigated in comparison to the pathological, non-lactating breast. Although ultrasound imaging is
only semi-quantitative and can be subjective, it may
provide information on the proportion of glandular tissue
560
in mothers with very low milk supply, 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 lactation, 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 body mass index 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 indicative of a blocked duct and should not be considered
“normal” for the lactating breast. Furthermore, the ultrasound scan may identify the level of the blockage,
providing useful information for treatment with therapeutic ultrasound.
Mothers of premature and sick infants rely on breast
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
compression of superficial ducts within the breast by the
shield may indeed compromise milk flow. Further research is required to determine the effect of ductal
anatomy on pumping performance in women.
Many women who have breast reduction surgery may
be able to partially breastfeed their infant, but relatively
few are able to exclusively breastfeed.52 This is likely
because of the codistribution of glandular and fatty tissue
within both the lactating38 and non-lactating breast,53
making it difficult to preferentially remove fatty tissue. In
addition, milk outflow is probably disrupted, because
there are fewer numbers of ducts than previously
thought.21,38 Furthermore, it is possible that the milk
ejection reflex may be inhibited if the nerve supply to the
nipple is disturbed.
The absence of lactiferous sinuses or milk reservoirs
leads one to reconsider the mechanism by which the
infant removes milk from the breast. Generally, it is
believed that the predominant action involved in removing milk from the breast is peristalsis or a stripping
action.54 We have found that milk flows into the infant’s
mouth when its tongue is lowered and vacuum is applied
to the breast. This finding suggests that the vacuum
applied by the breastfeeding infant is a major component
of milk removal.55 Indeed, it is evident that correct
positioning and attachment of the infant to the breast is
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
Glandular anomaly
Hypoplasia
Hyperplasia
Breast surgery
Reduction
mammoplasty
Breast augmentation
Palpable mass
Blocked duct
Galactocele
Benign mass (cyst,
fibroadenoma)
Malignant mass
Infant sucking
mechanism
Milk expression
Milk ejection
Symptoms
Anatomical Relationship
Low milk production
Excessive breast growth,
lymphoderma, possible necrosis
Possible deficiency of glandular tissue
Excess glandular tissue
Low milk production
Large volume of glandular tissue removed, severing milk ducts (fewer in number than
previously thought); possible nerve damage inhibiting milk ejection reflex
Possible compression of milk ducts by implant
Possible deficiency in volume of glandular tissue
Low milk production
Mass (small or large) ⫾ pain
Possible reduction in milk
production
Mass (generally small)
Mass
Palpable non-resolving mass
Ineffective suck
Differences in efficiency of
pumping
Differences in effectiveness of
pumping
Time of increased milk availability
Compression of ducts: possible cause of blocked duct; if large lobe affected a significant
reduction in milk production may occur; identification of the level of duct obstruction
by ultrasound ensures treatment of entire affected area
Possible ductal abnormality
Possible compression of ducts causing blocked duct; possible obstruction of milk flow in
the area of attachment of the infant to the breast
Irregular shaped mass that may be mistaken for a blocked duct or galactocele;
ultrasound ⫾ mammography needed for diagnosis
Lack of milk sinuses and evidence that vacuum plays a major role in milk removal may
alter intervention
Theorized that women with large milk ducts or duct dilations at milk ejection express
milk quickly
Poor shield fit may result in compression of superficial ducts and inhibit milk flow
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
mechanism should be fully understood in order to diagnose and manage infants with sucking abnormalities.
Finally, the absence of the lactiferous sinuses further
emphasises the critical nature of milk ejection for successful breastfeeding, because only small amounts of
milk are available before the stimulation of milk ejection.40,46
MILK EJECTION
Milk ejection is critical for successful lactation, because
only small volumes of milk (1–10 mL) can be either
expressed46 or removed by the breastfeeding infant40
before milk ejection. Failure to remove sufficient quantities of milk results in a decrease in milk production
because of local control mechanisms.47 Stimulation of
the nipple initiates milk ejection via initiation of nervous
impulses to the hypothalamus, which stimulates the
posterior pituitary gland to release oxytocin into the
bloodstream.48 Oxytocin causes the myoepithelial cells
surrounding the alveoli to contract, forcing milk into the
ducts. This results in increased intraductal pressure,49
duct dilation40,50 (measured by ultrasound), and consequently increased milk flow rate50 (measured by continuous weigh balance during breast expression). Multiple
milk ejections almost always occur during breastfeeding40 (mean, 2.5; range, 0 –9) and breast expression50
(mean, 3– 6 for 15-minute expression period), and alJournal of Midwifery & Women’s Health • www.jmwh.org
though many women are able to sense the first milk
ejection, few are able to sense subsequent ones.
While it is well known that stress can influence milk
ejection—resulting in diminished amounts of milk removed by both the infant48 and breast pump51—it is
often the subtle stress which affects maternal confidence
and subsequently milk ejection that is overlooked. Therefore, it is important to provide positive support to the
mother during both breastfeeding and pumping. Another
factor that may influence milk ejection and milk removal
is the ductal anatomy of the breast. In a study of mothers
expressing with an electric breast pump, ultrasound was
used to image duct dilation in the breast that was not
pumped. It was found that mothers with larger ducts
expressed more milk during milk ejection and had longer
milk ejections than mothers with smaller ducts.50 Therefore, the rate of milk removal for a mother may be
influenced in part by her ductal anatomy.
CONCLUSION
New anatomy research has shown that the milk ducts of
the breast are small, compressible, superficial, and
closely intertwined. They do not display typical dilated
“sinuses” and do not typically store large amounts of
milk. In addition, the amount of adipose tissue in the
breast is highly variable, particularly between the glandular tissue. This fundamental knowledge of the anatomy
of the breast—particularly when it is fully functional—
561
allows one to begin to understand and the myriad of
problems that are experienced by women during lactation. This knowledge will form a foundation for the
development of appropriate treatments and interventions.
The author’s salary is funded by Medela AG.
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print version are subject to. The online-only articles appear in the Table of Contents of
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