The breasts

The breasts are paired structures located on the ventral thorax. The female breast consists of 10–20 lobes that are surrounded by connective and adipose tissue. Each lobe contains milk-producing glandular structures and multiple terminal duct lobular units that form the milk duct system and drain via the major milk ducts and the lactiferous sinuses to the nipple. Lactating lobules produce the breast milk that nourishes many newborns and protects them from infections (passive immunity). For more detailed information on lactation, see lactation and breastfeeding. The nipple also contains multiple nerve endings, which make it particularly sensitive to stimulation.

Overview

Location

• The breasts are paired structures located at the level of ribs 2–6, below the subcutis on the muscles of the ventral thorax.
• Divided into four quadrants: upper lateral, upper medial, lower lateral, and lower medial

Function

• Milk production
• Lactation
• Sexual arousal

General structure

• Mammary gland
  • Modified sweat gland
  • Organized into 10–20 lobes
  • The major ducts and lactiferous sinuses drain the milk to the nipple.
  • Rudimentary and usually non-functioning in men
• Interlobular mammary stroma: surrounds the glands and ducts with connective and adipose tissue
• Nipple-areolar complex
  • Mammary papilla (nipple)
    • Area in which the lactiferous (milk) ducts of the mammary glands join and open onto the skin
    • Typically surpasses the skin level
  • Areola
    • Surrounds the nipple
    • Disk with darker skin pigmentation
    • Areolar glands (Montgomery tubercles): small sebaceous glands

Ligaments and fascia

The mammary glands are attached to the skin and chest wall by strong bands of connective tissue.

• Pectoral fascia
  • Located dorsal to the breast
  • Connected to the breasts through loose connective tissue (retromammary space)
  • Attachment point for the Cooper ligaments
• Suspensory ligaments of the breast (Cooper ligaments)
  • Strong bands of connective tissue
  • Run between the dermis and the pectoral fascia
  • Support the form of the breasts
  • Separate the secretory lobules

Vasculature and innervation

The breasts are supplied by the intercostal and axillary pathways.

• Arteries
  • Medial breast: medial mammary branches of the internal thoracic artery from the subclavian artery
  • Lateral breast
    • Lateral thoracic and thoracoacromial branches from the axillary artery
    • Mammary branches of the posterior intercostal arteries (2^nd–5^th ICS) from the thoracic aorta
    • Mammary branch of the anterior intercostal artery
• Veins
  • Internal thoracic vein → subclavian vein
  • Lateral thoracic vein → axillary vein
  • Intercostal veins → azygos vein (right), hemiazygos and accessory hemiazygos veins (left) → superior vena cava, vertebral venous complex
  • Areolar venous plexus → axillary vein
• Innervation (sensory and autonomic fibers )
  • Supraclavicular nerves of the cervical plexus
  • Lateral and anterior cutaneous branches from intercostal nerves 2–6
• Lymph nodes of the breasts
  • Three groups
    • Axillary lymph nodes
      • Number of nodes: 30–60
      • Provide 75% of the lymphatic drainage of the breast
    • Parasternal (internal thoracic) lymph nodes
      • Drain most of the medial parts of the breast
      • Lie along the internal thoracic arteries
    • Posterior intercostal nodes: (provide 5% of the lymphatic drainage of the breast)
  • The skin of the breasts drains to axillary, inferior deep cervical, and infraclavicular nodes.

Secretion of milk is not mediated by the nerves but by the hormone prolactin.

A tumor infiltrating the breast tissue can deform, shorten, and retract the Cooper ligaments and lead to dimpling of the skin. Tumorous infiltration and blockage of the lymphatics manifest as lymphedema and thickening of the skin, which is known as peau d'orange because of the resemblance to orange peel. Retraction of the nipple can be a sign of a tumor within the ducts (Paget disease of the breast).

Carcinomas of the breast metastasize early on through the lymph pathways. As most carcinomas of the breast develop in the upper lateral quadrant, lymph node metastases often occur in the axilla of the same side.

References:^[1]

Non-lactating breasts

The lobes of the breasts consist of multiple smaller lobules with milk ducts. The milk duct system of the lobules joins to form one main milk duct per lobe.

Terminal ductal lobular units (TDLU)

• Basic histopathological units of the mammary gland
• Consist of:
  • Lobule of the mammary gland: (functional unit of the breast)
    • Intralobular stroma: loose, cell-rich connective tissue
    • Intralobular terminal (milk) duct with multiple outpouchings called acini or ductules (site of milk production)
      • Structure: tubulo-alveolar with two-layered glandular epithelium
        • Outer layer: myoepithelial cells (contractile, route the milk to the ducts in lactating breasts)
        • Inner layer: cubic, apocrine glandular epithelial cells (can produce milk)
  • Extralobular terminal duct

Milk duct system

• Function: transports the milk from the terminal duct to the endpoint of the nipple
• Structure: two-layered epithelium
  • Inner layer: prismatic epithelium cells
  • Outer layer: myoepithelial cells
• Parts
  • Terminal ducts or lactiferous ducts: excretory duct of a single lobule
    • Contains stem cells to facilitate cell proliferation that enables lactation
    • Collect milk from alveoli (which are lined with lactocytes which synthesize breastmilk)
  • Major ducts: largest part of the milk duct system
    • Confluence of the terminal ducts
    • Run towards the nipple (in radial form) and extend into the lactiferous sinus
  • Lactiferous sinus:
    • Dilated end of lactiferous ducts (reservoir for milk)
    • Extends and opens out into the nipple

After skin cancer, breast cancer is the most common malignancy in women. Depending on the tissue in which malignancy originates, breast cancers can be histologically differentiated into ductal carcinoma (originating from the milk duct epithelium) and lobular carcinoma (originating from the lobules). Invasive ductal carcinoma of the breast is the most common type.

Lactating breasts

The transition from non-lactating to lactating breasts already begins in the first trimester of pregnancy. During this time, the mammary gland increases in size, and the production of breast milk is initiated.

• Changes in the mammary gland
  • Enlargement and differentiation of the lobules of the mammary gland
  • Tubulo-alveolar glands of the lobules initiate lactation
  • ↓ Interlobular stroma
  • ↑ Vascularity
• Changes in the nipple
  • ↑ Size, ↑ pigmentation
  • Montgomery tubercles become visible
• Hormonal regulation of the transition of the glands
  • Estrogen: ↑ cell proliferation and hypertrophy of the milk duct system
  • Progesterone, estrogen, and prolactin: ↑ cell differentiation and proliferation of the lobules
  • Prolactin: production of milk

Lactating breasts have distinct histological features: very large lobules with tubulo-alveolar ends and only small amounts of connective tissue between the lobules! Because of the reduced amount of stroma, histological preparations of lactating breasts can be confused with those of the prostate or of the parathyroid gland!

Menstrual cycle-dependent and age-dependent changes of the breasts

The size and perfusion of the mammary glands vary during the menstrual cycle, but they also change in the course of a woman's lifetime.

• Menstrual cycle
  • Proliferative phase: no changes
  • Secretory phase: ↑ estrogen and ↑ progesterone → cell proliferation, ↑ number of acini, edema of interlobular stroma
  • During menstruation: desquamation and regression
• Puberty: See “Embryology of the breast“ and “Tanner stages.”
• With age: involution of the breasts with the onset of menopause due to a decrease in estrogen levels
  • Atrophy of mammary glands and connective tissue stroma
  • The milk duct system is preserved.
  • Relative increase in fat percentage

The mammary glands initially develop as mammary ridges from the embryonic surface ectoderm. The development of the breasts is identical in all sexes until puberty. Glandular tissue only begins developing at puberty.

Development of mammary glands ^[2][3]

• Development of the mammary ridges (milk lines) ^[3]
  • Cutaneous crest from which multiple glandular buds originate
  • Develop vertically on both sides from the axilla to the groin from the 5^th week on
  • Thickening of the ectoderm (milk line)
  • Thickening spreads increasingly into the subepithelial connective tissue, at which point it is called the mammary ridge.
• Regression of excess mammary ridges
  • The accessory mammary ridge regresses.
  • Only the thoracic mammary bud of each side of the body remains.
• Sprouting of two epithelial buds
  • The two remaining epithelial buds sprout beneath the epidermis → development of first glandular lumina
• Eversion of the nipple
  • Initially, the nipple is level with the skin.
  • Excretory ducts of the glandular lumina are everted → The nipple surpasses the level of the skin.
  • Development and growing pigmentation of the nipples and areolas

If the regression of the mammary ridge is impaired, more than two epithelial buds may remain. In this case, accessory nipples (polythelia) or breast tissue (polymastia) may develop. Total regression of nipples (athelia) and breast tissue (amastia) can also occur.

Maturation of the mammary gland

In puberty, the development of the mammary gland is sex-specific. Breast development in women during puberty is also called thelarche.

• Changes of the female breasts during puberty
  • Increase of tissue in the area of the areola with slight protrusion
  • ↑ Estrogen stimulates the development of breast tissue.

Because men do not have the same hormonal influxes of estrogen, their mammary glands remain rudimentary. Nevertheless, men can also develop carcinoma of the breast.

Maternal pregnancy hormones can also prepare the mammary glands of newborns for lactation. The mammary glands of newborns may be slightly swollen after birth and produce a milky secretion (i.e., witch's milk or neonatal milk).

• Benign breast conditions
  • Fibrocystic changes
  • Mastitis
  • Fat necrosis
  • Gynecomastia
  • Fibroadenoma
  • Congenital anomalies of the breast
• Breast cancer
  • Ductal carcinoma in situ
  • Lobular carcinoma in situ
  • Invasive ductal carcinoma
  • Invasive lobular carcinoma
  • Inflammatory breast cancer
  • Paget disease of the breast
• Nipple discharge
• Mammography
• Puberty and Tanner stages
• Differences (disorders) of sex development (e.g., Klinefelter syndrome, Turner syndrome)
• Lactation and breastfeeding
• Aging (breast atrophy)