The mammary gland develops through distinct stages in females. During puberty, estrogen and progesterone stimulate ductal growth and lobular development. In pregnancy, placental hormones induce remarkable lobuloalveolar growth. Lactation is stimulated by prolactin and oxytocin to produce milk. Menopause causes glandular tissue shrinkage. Disorders include cancers, cysts, and fibroadenomas. Diagnosis involves exams, imaging, and biopsies. Treatments range from surgery to chemotherapy and reconstruction.
2. SYNOPSIS
INTRODUCTION
ANATOMY OF THE MAMMARY GLAND
HORMONAL CONTROL IN THE MAMMARY GLAND
DEVELOPMENT
DISORDERS
DIAGNOSIS
TREATMENT
CONCLUSION
3. INTRODUCTION
Mammary glands are the organs that, in the female produce milk for the sustenance of the
young.
The word “mammary” comes from “mamma” the Greek and Latin word for the breast.
These exocrine glands are enlarged and modified sweat glands and are the characteristic of
mammals which gave the class its name.
The human mammary gland is the “Breast”.
In human females , the breast are one of the secondary sexual characteristics and develop in
response to the hormonal changes accompanying puberty (William C.Shiel 2012).
In human, the breast is formed in both the sexes,
Male – Rudimentary
Female – well developed after puberty.
• The advantage of the mammary gland was that it provided for a ready source of nutrition
for the still developing infant, obviating the need for prolonged incubation in a fragile and
vulnerable egg encasement (Oftedal et al.,2002).
4. ANATOMY OF THE MAMMARY GLAND
Topographical location
- Second to sixth rib.
- Lies in the superficial pectoral fascia
-.Retromammary space.
- Attached by Cooper ligaments.
- Covered by Pectorial major muscles.
Weight of the breast
- Non pregnant : 200g
- Pregnancy near term : 400-600g
- lactation : 600-800g
Shape of the breast
- Dome like shape
(conical in nulliparous, unevenly
hemispherical in parous women)
5. Structure :-
3 major structures
- The Skin
- The Corpus Mammae (body of the breast)
- The Subcutaneous tissue
The Skin :-
Thin, flexible, adherent to the subcutaneous tissue.
- The Nipple :
Conic elevation, slightly below midpoint of breast,
containing 15-25 milk ducts, sensory nerve endings,
abundant sebaceous and apocrine
sweat glands, no hair.
- The Areola :
Circular Pigmented skin, area 15-60 mm in
diameter, contains Montgomery glands, sweat
glands and smaller sebaceous glands.
6. Corpus Mammae -
(body of the breast)
The Parenchyma –
consists of glandular tissue which secretes milk
consists of 15-20 lobes (converging on the nipple)
each lobe – cluster of alveoli (0.12 mm in diameter)
drained by lacteriferous ducts ( 2mm in diameter)
near its termination, each duct has a dilation-
lactiferous sinus
converge towards the nipple and open on it.
• The Parenchyma
• Stroma
7. Under the influence of sex steroids ( especially estrogens) the mammary glandular
epithelium proliferates . It becomes multilayered and begins to differentiaites.
The different cell types in the epithelial
Glandular structure of the breast:-
• Basal B-cells
• Superficial (luminal)
A-cells
• Myoepithelial cells
Basal B cells
8. Basal B- cells ( Chief cells )
Preponderate in number.
Essential structural elements of the mammary epithelium.
Cytoplasm – clear and transparent.
Nuclei – round or ovoid, equal chromatin distribution.
Smooth cell membrane held together by hemidesmosomes.
Reach the alveolar lumen and develop apical microvilli.
Functions as stem cells for myoepithelial and luminal A-cells.
division
Basal alveolar clear B cells
Stem cell
Insulin
Cortisol
EGF
GH
HPL differentiaition
Other Stem cells
Luminal A-cells
Myoepithelial cells
9. Superficial (Luminal) A-cells:-
Rich in ribosomes – appear dark.
Cytoplasm- large amounts of RNA and ergastoplasm.
Nuclei rich in chromatin, nucleoli prominent.
Secretory activity more than basal clear cells.
Estrogen – induces proliferation.
Show intercellular dehiscenses- “superficial regressive cells”.
The epithelium of the mammary duct also consists of dark luminal cells and clear
basal cells.
Myoepithelial Cells :-
Inner aspects of the basal membrane – “envelope”.
Cells are denser and more contractile.
Contains myofilaments – 50-80 Å in diameter.
Nucleus – ovoid, dense, relatively small.
Hormonally stimulated by sex steroids and
prolactin.
Proliferate during pregnancy and lactation.
10. Role of Myoepithelial cells during lactation –
The mammary alveoli are dilated and filled with milk
The surrounding myoepithelial cells are relaxed.
(Stimulated by the
baby’s suckling )
Endogenous oxytocin released.
Contraction of the myoepithelial cells and smaller milk ducts
Ejection of milk from the alveoli into lactiferous ducts and lactiferous sinuses
and finally to the nipple , where the milk is removed by the suckling baby.
11. Additional types of cells found in the mammary gland and the surrounding stroma
- Adipocytes, Fibroblasts, Plasma cells, blood vessels.
Hormones and their Receptors:-
• Estrogen – mammary ductal development.
ER predominantly expressed in the luminal cells and also in the nuclei of the ductal
epithelial cells.
• Progesterone – side branching of the mammary duct .
PR expressed in the luminal epithelial cells of the duct and the lobules.
• Prolactin, Placental lactogen – alveolar bud formation and milk production.
Growth Factors :-
• TGFß Superfamily :- Gland development
• EGF – Mammary cell proliferation and differentiation
• IGF – Regulates hormonal control of the ductal growth and ductal branching.
(Hartmann et al.,1973)
12. Mammary Blood Supply:-
The mammary gland is extremely vascular.
Arterial Supply of the breast:-
Lateral (mammary) thoracic artery
(branch of the axillary artery).
Internal (mammary )thoracic artery
(branch of the subclavian artery).
Lateral branches of the posterior
Intercostal arteries.
The arteries bring oxygen and nutrients
And converge on the breast.
They are distributed from the anterior
Surface. The posterior surface is
extremely avascular.
13. Venous supply of the breast:-
The veins follow the arteries.
Lateral Thoracic vein runs with Lateral Thoracic artery.
Internal Thoracic vein runs with Internal Thoracic artery.
Intercostal vein runs with Intercostal artery.
Additional venous drainage of the breast – Cephalic Vein
14. Nerves of the Breast:-
Cutaneous Innervation
Medial Pectoral Nerve
Lateral Pectoral Nerve
Long Thoracic Nerve
15. Lymphatics of the breast:-
Drains lymph from the breast to a series of nodes.
Lymph drainage:-
Cutaneous/superficial
Areolar
Glandular / deep tissues
Lymph nodes of the breast:-
Pectoral (anterior) nodes
Subscapular (posterior) nodes
Humeral (lateral) nodes
Central nodes
Apical nodes
Interpectoral nodes.
Parasternal nodes
16. Clinical Significance of Breast Lymphatics:-
Cancer cells tend to spread along the lymph passages.
Typical spread is laterally to the axillary lymph nodes.
More than 75% of drainage through axillary lymph nodes.
Most remaining drainage is medially to parasternal nodes.
5 to 6% of all women suffer from breast cancer during their life cycle, the lymphatic
drainage of the breast is of particular clinical importance.
17. HORMONAL CONTROL IN THE MAMMARY GLAND
DEVELOPMENT
Breast development is a vital part of reproduction in the human female. Breast
development occurs in distinct stages throughout a woman’s life, first before birth ,
again at puberty, and during the child bearing years. Changes also occur to the breasts
during menstruation and when a woman reaches menopause.
Factors that may influence a woman’s breast size includes :
Volume of breast tissue
Family History
Age
Weight loss or gain
History of pregnancies and lactation
Thickness and elasticity of the breast skin
Degree of hormonal influences on the breast (particularly estrogen and
progesterone)
Menopause
18. Embryonic and Fetal Mammary Development
Week 5: Development of “milk
ridge”
Week 6: “ Milk Hill Stage” – Thickening of the
epidermis
Week 7 -9 : Globular protrusion of the
overlying skin,
invasion of the mesenchymal
cells.
Incomplete regression of the primitive
mammary streak: “supernumerary
mammary tissues”
19. Week 10-15: Further invasion & differentiation
of the mesenchymal cells.
Neck-shaped thinning of the
parenchymal cells.
Development and folding of the
“epithelial buds”
4 months: Appearance of basal epithelial
tissue sprouts.
Formation of secondary
mammary buds.
•These early stages of mammary development are independent of specific hormonal effects.
•Last trimester of pregnancy:- Placental sex steroids enter the fetal circulation and induce
pronounced breast stimulation.
20. Month 6-8: Canalization of secondary
mammary buds.
Formation of 15-25 tubules.
Formation of glandular lumina
Increased vascularization
Formation of connective
tissues and fat.
Month 9-10: Mass increases four fold.
Parenchymal differentiation into
“lobular– alveolar structure”.
Increased pigmentation of the
areola region.
15-25 milk ducts merge into the
indented centre.
21. Mammary gland development of the newborn and the child
• A hemispherical elevation of the mammary disc
• Peripheral lobuli of the newborn’s mammary gland enlarged.
• Secretorily active alveoli.
• 2-3 days postpartum – colostral secretion in
80-90% newborns.
• Colostral milk secretion subsides with 3-4 weeks ,
due to decline in prolactin secretion.
• Glandular tissues involutes.
Throughout childhood, the rudimentary mammary tissues are quiescent. The
Nipple does not protrude and only slight branching of the primary mammary
ducts are observed.
22. Mammary gland development during Puberty
Combined influence of estrogen and progesterone – development of the breast into its
adolescent size, firmness and lobular-alveolar structure.
Stimulates the growth and elongation of the mammary ducts.
Induce proliferation of the terminal ductular parts
Volume and elasticity of the periductal connective tissue increases.
Mammary vasculature and fat deposition becomes enhanced.
Distinct elevation of the nipple and the areola.
During the adolescent years , the mammary duct grows larger and continue to differentiate
into “lobular alveolar structure”.
After the age of 15, definite shape of the mature breast is gradually formed.
Support of breast tissue maturation :-
Insulin, Cortisol, TH, Parathyroid hormone, Growth hormone.
23. Menstruation
Estrogen:-
- Induces parenchymal proliferation.
- Stimulates cellular RNA synthesis,
- The density of the nucleus increases ,
- Other cellular organelles increase in
number.
Progesterone:-
- Dilation of the mammary ducts.
- The mammary alveolar cells differentiate
into secretory cells.
- Enhanced mammary blood flow.
- Breast volume is increased by 15-30cm3
Just before menstruation – swelling, pain and tenderness.
During menstruation – changes in breast texture (lumpiness)
Menstruation prepares the breasts and ovaries for potential pregnancy.
24. Pregnancy and Lactation
A remarkable ductular-lobular-alveolar growth occurs during pregnancy :–
- luteal and placental sex steroids, placental lactogen, prolactin and Hcg.
First trimester:-
Estrogen induces ductular sprouting and branching.
Beginning of the lobular formation.
Dilation of the superficial veins and a feeling of heaviness.
Pigmentation of areola and nipple is intensified.
Change of the 2 cell layer alveolar epitheilium into a monolayer secretory unit.
25. Second Trimester:-
Intensified Ductal Proliferation.
Formation of lobular-alveolar structure.
Appearance of lymphocytes in the surrounding
connective tissues.
Increased activity of the secretory epithelial cells.
Accumulation of colostrum within the mammary
alveoli.
Third Trimester:-
Increased accumulation of intraplasmic fat droplets in alveolar epithelial cells.
Progressing dilation of mammary alveoli by enhanced secretion of colostrum.
Division and differentiation of mammary epithelial stem cells into milk synthesizing
pre-secretory cells, myo-epithelial cells and other stem cells.
180% increase of mammary blood flow.
Each breast gains approximately ¾ lb in weight and becomes firm, full and ready for
lactation.
26. Lactation:-
Two hormones responsible for milk production – Prolactin and Oxytocin.
Prolactin acts on presecretory alveolar cells , to stimulate the expression of genes
encoding proteins that are secreted in the milk
- Caesin and lactalbumin and also the proteins that regulate the synthesis
of lactose and triglycerides.
27. Oxytocin is secreted in response to suckling.
Oxytocin stimulates the contraction of myoepithelial cells surrounding each alveoli –
allows the pressurized milk to be ejected into the infant’s mouth.
During the first few days of birth , the body produces colostrum- contains antibodies
to help protect the infant against infections.
Weaning:-
Decreased prolactin secretion .
Absence of mechanical stimulation.
After weaning, there is only partial involution. All alveoli and secretory duct
structures collapse by apoptosis and autophagy – lack of growth promoting factors. This
Leads to loose fat tissue which fills the empty space afterward.
But a functional lactiferous duct tree can be formed again when a female is pregnant
again (Zarzynska.J et al., 2008).
28. Menopause
Menopause – estrogen and progesterone production stops.
The breast glandular tissue shrinks and is replaced with fatty tissue.
The fibrous (connective) tissue becomes inelastic and loses its strength – leading to
the sagging of the breasts.
For some women, the breasts become more tender and lumpy, sometimes forming
cysts.
29. DISORDERS OF THE MAMMARY GLAND
Breast Cancer
Ductal carcinoma in situ (DCIS)
Lobular carcinoma in situ (LCIS)
Invasive ductal carcinoma
Invasive lobular carcinoma
Simple breast cyst
Breast fibroadenoma
Fibrocystic breast tissue
Usual hyperplasia of the breast
Atypical hyperplasia of the breast
Intraductal papilloma
Adenosis of the breast
Phyllodes tumor
Fat necrosis
Mastitis
Breast calcifications
Gynecomastia
(Bieber et al., 2006).
30. DIAGNOSIS
Physical examination
Mammogram
Digital mammogram
Breast ultrasound
Breast Magnetic Resonance Imaging (MRI) scan
Fine needle aspiration (FNA) breast biopsy
Core needle breast biopsy
Surgical biopsy
Sentinel node biopsy
Nipple smear ( nipple discharge exam )
(Bieber et al., 2006).
31. TREATMENTS
Lumpectomy
Mastectomy
Axillary lymph node dissection
Chemotherapy
Radiation therapy
Breast reconstruction
Antibiotics
Breast augmentation
Breast reduction
(Bieber et al., 2006).
32. CONCLUSION
The human breast is a dynamic organ which is
continuously remodeled under the influence of hormones and
growth factors. It is thought that this intrinsic dynamic ability
of the breast cells to be continuously influenced and remodeled
makes them especially susceptible to carcinogenesis (Beatrice
.A.Howard et al., 2000).
33. BIBLIOGRAPHY
Beatrice A.Howard and Barry A.Gusterson (2000) – “Human Breast Development”, Journal of
Mammary Gland Biology and Neoplasia. Vol 5, No 2.
Chaurasia’s, B.D (2004) – Human Anatomy (Volume 1)
Fadok, V.A (1999) - Clearance: the last and often forgotten stage of apoptosis. J Mammary Gland
Biol Neoplasia, 4(2): p. 203-11.
Helmuth Vorherr (1974) – The Breast
Karen M.Bussard and Gilbert H.Smith (2011) – “The Mammary Gland Microenvironment
Directs Progentitor Cell Fate In Vivo”.
Lefèvre C.M., Sharp J.A., Nicholas K.R. (2010) - "Evolution of lactation: ancient origin and
extreme adaptations of the lactation system". Annual Review of Genomics and Human Genetics (11):
219–238.
Oftedal, O.T. (2002) - "The origin of lactation as a water source for parchment-shelled “, Journal
of Mammary Gland Biology and Neoplasia 7 (3): 253–266
Dr.Roger.A.Dasher – Clinical Anatomy of the Breast
Zarzynska J, Motyl T (2008) - Apoptosis and autophagy in involuting bovine mammary gland. J
Physiol Pharmacol. 59 Suppl 9:275-88.