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Anatomy and Physiology

of the Breast 1

1.1 Anatomy of the Breast lobe or segment of the breast comprises branch-
ing ducts and terminal secretory lobules which
The anatomy of the breast has been well docu- converge into 15–20 larger lactiferous ducts that
mented (Bannister 1995). The adult breast is a open onto the apex of the nipple. The number and
fibroadipose organ that sits on the anterior upper size of these terminal secretory lobules vary
thorax, extending from the second through the greatly in different individuals and at different
sixth ribs and from the sternum to the anterior periods of life – they are most numerous during
axillary line, with an axillary tail in the upper the reproductive age and are fully developed only
outer portion that can be palpated along the outer during pregnancy and lactation. The lactiferous
border of the pectoralis major muscle. It forms a sinuses or ampullae are short dilated portions of
secondary sexual characteristic of females, pro- the lactiferous ducts that lie partly within and
viding nutrition to their young, while it is rudi- deep to the nipple, in which milk may be stored.
mentary in males. It lies upon the deep pectoral
fascia, overlying the pectoralis major and serra-
tus anterior. The nipple protrudes from the center 1.2 Physiology of the Breast
of the breast anteriorly, while the areola is the
discoidal skin that encircles the nipple. The areo- 1.2.1 Development
lar surface appears rough because of the presence
of large modified sweat glands called the glands Mammary development occurs during the 15th
of Montgomery, which are located beneath the week of fetal gestation, with condensation of
skin and whose fatty secretions serve to lubricate mesenchyme around the epithelial stalk of the
the nipple. Smooth muscle bundles in the areolar breast bud (Rosen 2009). Together with dermal
tissue help to stiffen the nipple for better grasp papillary and reticular layers which form the
during suckling by the infant. The breast consists fibrous connective tissue of the breast, the epithe-
of 15–20 segments and has components of epi- lial stalk becomes the ductal system of the breast
thelial glandular tissue, fibrous connective tissue lobe. Myoepithelial cells form from basal cells
that surrounds the glandular elements, and inter- during the 23–28th weeks of gestation. The mes-
lobar adipose tissue. The relative amount of enchyme differentiates into fat between the 20th
fibrous and adipose tissue determines the size and 32nd weeks. Fetal breast development
and consistency of the breast in the nonpregnant, depends on a combination of growth and differ-
nonlactating female. The fibrous connective tis- entiation factors as well as bcl2 and testosterone.
sue is continuous with the pectoralis fascia and During the late third trimester, maternal and pla-
also sends strands, called the suspensory liga- cental steroid hormones and prolactin result in
ments of Cooper, into the overlying skin. Each secretory activity in the fetal breast. After birth,

G. Tse et al., Fine Needle Aspiration Cytology of the Breast, 1


DOI 10.1007/978-3-642-35000-9_1, © Springer-Verlag Berlin Heidelberg 2013
2 1 Anatomy and Physiology of the Breast

Fig. 1.1 Normal breast


acinus comprising a wreath
of luminal epithelial cells
and occasional myoepithelial
cells (arrows). Scattered
bipolar naked nuclei are seen
in the background

the neonate may have palpable breast enlarge- depends on insulin, progesterone, and growth
ment which subsides after maternal hormones hormone. Lobular growth and development con-
disappear from the infant’s bloodstream. During tinue from puberty until adulthood and are further
childhood, the breast remains in an inactive state enhanced during pregnancy and lactation.
with histological ducts without alveolar or acinar
differentiation.
In premature thelarche, there is unilateral or 1.2.3 Menstrual Cycle
bilateral breast enlargement before puberty due
to abnormal levels of endogenous hormones. The During the menstrual cycle, physiologic variation
nodular breast tissue of premature thelarche tends of hormonal levels can lead to changes in the
to regress spontaneously. It is important to recog- breast, including size and consistency. It is
nize this condition, as surgical excision will lead believed that the breast is less nodular at the
to amastia. Histologically, premature thelarche mid-phase of the menstrual cycle as well as in the
shows gynecomastoid appearances with ducts later follicular phase and is thus optimal for clini-
devoid of acini, demonstrating solid and micro- cal breast examination during this period.
papillary patterns of usual ductal hyperplasia. Radiologically, the breast is also least dense dur-
FNAC is generally paucicellular, with scattered ing the follicular than luteal phase of the men-
benign bimodal aggregates within a background strual cycle. The breast is more voluminous in the
containing a few bipolar stromal cells and myx- luteal phase due to increased parenchymal water
oid material (Fig. 1.1). content.
Histologically, the proliferative phase of the
menstrual cycle is accompanied by increased
1.2.2 Puberty and Menarche mitoses and apoptosis in the breast epithelium,
without luminal formation or secretory activity.
At puberty, there is onset of cyclical estrogen and Myoepithelial cells are difficult to discern. The
progesterone secretion that initiates adolescent lobular stroma is dense. The follicular phase
breast development. Estrogen, growth hormone, shows decreased mitotic activity and more dis-
and glucocorticoids stimulate ductal growth, cernible myoepithelial cells that may assume
while periductal stromal development is depen- clear cytoplasm. Lumens are better visualized,
dent on estrogen. Lobular and acinar formation and the intralobular stroma becomes loose.
1.2 Physiology of the Breast 3

Fig. 1.2 Lactational


changes. Corresponding
histology shows dilated acini
lined by cells with variably
sized nuclei, containing
luminal pink secretions

During the luteal phase, myoepithelial cells are confirmed in other studies (Markopoulos et al.
increasingly prominent with cytoplasmic glyco- 1988; Weimer and Donegan 1987; Smyth et al.
gen accumulation and clearing. Modest secretory 1988).
activity is noted. In the secretory part of the cycle,
there is distention of glands with secretions.
Lobular stroma is maximally edematous. The 1.2.4 Pregnancy and Lactation
menstrual phase is marked by loss of stromal
edema with infiltration by inflammatory cells into Pregnancy results in hypertrophy and hyperplasia
the lobule. Glandular lumens may be obscured, of lobular acini with secretory changes which can
and mitotic activity is absent. occur unevenly in the breast (Rosen 2009).
Detection of estrogen and progesterone recep- Pregnancy-related hyperplasia is most prominent
tors in breast epithelium is reported to vary dur- in the third trimester and can present as palpable
ing the menstrual cycle with highest expression lumps that are histologically lactational ade-
of estrogen receptor and progesterone receptor in nomas. Lobular enlargement commences in early
the proliferative and follicular phases, respec- pregnancy with accompanying reduction in
tively (Silva et al. 1983). There are also reports of stroma. Increased stromal vascularity and influx
greatest expression of both estrogen and proges- of inflammatory cells are noted. In the second
terone receptors in the follicular phase (Fabris and third trimesters, there is progressive lobular
et al. 1987). Immunohistochemical detection of growth. Microscopically, luminal epithelial cells
estrogen receptor was noted in 31 % of samples show cytoplasmic vacuolation, while myoepithe-
obtained on FNAC during the first half compared lial cells become indistinct. Luminal secretions
to its absence in the second half of the menstrual are seen in acini of the markedly expanded lob-
cycle (Markopoulos et al. 1988). Similarly, estro- ules. Stroma is diminished (Fig. 1.2). Alterations
gen receptor in breast cancer is reported more continue into lactation. FNAC of the pregnant or
frequently in the follicular than in the ovulatory lactating breast shows a cellular yield with epi-
or luteal phases, while progesterone receptor is thelial cells harboring open vesicular nuclei and
more expressed in the ovulatory than in the folli- conspicuous nucleoli, accompanied by lipopro-
cular and luteal parts of the menstrual cycle teinaceous secretory material in the background
(Pujol et al. 1998), though these observations are (Fig. 1.3). Epithelial cell cytoplasm tends to
not statistically significant and have not been be frayed, and these cytologic changes may
4 1 Anatomy and Physiology of the Breast

Fig. 1.3 Lactational


changes. The smear shows
cohesive epithelial clusters
with many dispersed naked
nuclei in a lipoproteinaceous
background

Fig. 1.4 Lactational


changes. Higher
magnification of the
dispersed cells which show
slight nuclear enlargement
and variability in size, with
discernible nucleoli.
Cytoplasm is indistinct, and
the lipoproteinaceous
background incorporates
some debris

occasionally be overinterpreted as atypical, sus- Some macrophages are seen in the lobule. The breast
picious, or even malignant, especially when eventually returns to its fibrofatty consistency.
superimposed on an underlying lesion such as a
fibroadenoma (Fig. 1.4).
Involution after cessation of lactation takes 1.2.5 Menopause
about 3 months. Secretion of milk stops when
prolactin levels decreases. Epithelial cells Breast changes during menopause occur in
undergo desquamation and phagocytosis, and response to decreased estrogen and progesterone
the number of lobules and acini diminishes. levels whereas androgen levels are not reduced
References 5

(Rosen 2009). There is a decrease in the number of Markopoulos C, Berger U, Wilson P et al (1988) Oestrogen
lobules and acini with epithelial atrophy accompa- receptor content of normal breast cells and breast car-
cinoma throughout the menstrual cycle. Br Med J
nied by thickening of acinar basement membranes 296:1349–1351
and occasional calcifications. Like pregnancy and Pujol P, Daures JP, Thezenas S et al (1998) Changing
lactation, the changes are uneven throughout the estrogen and progesterone receptor content of primary
breast. Myoepithelial cells are relatively spared by breast carcinoma during the menstrual cycle and
menopause. Cancer 83:698–705
the process of menopausal atrophy and appear Rosen PP (2009) Anatomy and physiological morphol-
prominent. Administration of hormone replace- ogy. In: Rosen PP (ed) Rosen’s breast pathology,
ment therapy may attenuate these alterations. 3rd edn. Lippincott Williams and Wilkins,
Philadelphia
Silva JS, Georgiade GS, Dilley WG et al (1983) Menstrual
cycle-dependent variations of breast cyst fluid proteins
References and sex steroid receptors in the normal human breast.
Cancer 51:1297–1302
Bannister LH (1995) Integumental system: skin and Smyth CM, Benn DE, Reeve TS (1988) Influence of the
breasts. In: Standrirng S (ed) Gray’s anatomy. The menstrual cycle on the concentrations of estrogen and
anatomical basis of medicine and surgery, 38th edn. progesterone receptors in primary breast cancer biop-
Churchill Livingstone, London sies. Breast Cancer Res Treat 11:45–50
Fabris G, Marchetti E, Marzola A et al (1987) Weimer DA, Donegan WL (1987) Changes in estrogen
Pathophysiology of estrogen receptors in mammary and progesterone receptor content of primary breast
tissue by monoclonal antibodies. J Steroid Biochem carcinoma during the menstrual cycle. Breast Cancer
Mol Biol 27:171–176 Res Treat 10:271–278

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