BREAST EMBRYOLOGY

The breast or mammary gland (lat. mamma, grc. mastos) is the largest skin gland.  That is modified sweat gland.  It exists in the male as well as in the female, but in the former only in the rudimentary state (2) (figure 1).
At the end of the first month of embryonic development, the mammary gland begins to develop as a solid bud of epidermis into the underlying mesenchyme (figure 2).  This primary bud occurs from cranial part of the mammary ridges, thickened strips of ectoderm.  Each primary bud give rise to several secondary buds that develop into the lactiferous ducts and their branches that make up the mammary gland.
During pregnancy that the breast assumes its complete morphologic maturation and functional activity (figure 4 and figure 5).

ANATOMY AND HISTOLOGY OF BREAST

 Breast is a symmetric double organ.  It reaches normal size between 16 to 19 years (figure 4). It is situated toward the lateral aspect of pectoral region, corresponding to the interval between the second and the seventh rib and extending from lateral side of the sternum to the axilla (8, 9). Radix of breast (radix mammae) is situated under second rib, extending into body (corpus mammae).  Breast is covered by skin that in the lower part makes sharp flexure like a groove (sulcus submammalis) and becomes skin of pectoral region (figure 6) (8, 9).

On the top of the breast is a small conical prominence, the nipple (papilla mamme).  The nipple is surrounded by an areola, pigmented area (figure 6) (8, 9).

The breast is consisted of gland- tissue that is embedded into connective tissue and padded with fat tissue (figure 7).  The gland tissue is divided into 10 to 20 sections called lobes and is composed of lobules connected together by connective tissue (figure 8 and figure 9).  Lobules are structured as a small milk- producing gland.  This structure is responsible that during palpation of the gland tissue feels granular formation.  Each lobe has its own draining duct.  They converge toward the areola, beneath which form dilatation (sinus lactiferus), and again become contracted and narrow before opening at the nipple.  Lobes and its ducts are radial lined around nipple, therefore each section should be radial toward nipple (8-13).

The arteries supplying the breast are derived from lateral thoracic artery, internal thoracic artery and intercostal arteries.  Internal thoracic arteries and its perforating branches supply a medial part of the breast.  Lateral thoracic artery supplies a lateral part of the breast.  Profound part is supplied by intercostal arteries and theirs branches (8).

The veins describe an anastomotic circle round the base of the nipple, called by Haller circulus venosus.  From this, large branches transmit the blood from medial part of the breast into internal thoracic veins and from the lateral part of the breast into lateral thoracic vein and intercostal veins (figure 10) (8).

The lymph vessels of the breast are situated into two layers (superficial and profound layers), making networks that are interconnected.  Superficial lymph vessels transmit the lymph fluid into axillary lymph nodes.  It is important to mention that some of the superficial lymph vessels transmit the fluid into axillary lymph nodes from the other side of the body, directly or indirectly using the lymph vessels from the other side.  The lymph fluid from region of nipple, areola and lateral part of the breast is transmitted into axillary lymph nodes along inferior margin of the pectoral major muscle.  From the lateral part, lymph fluid is firstly transmitted to the intercostal lymph nodes and then to the axillary lymph nodes. From the superior and profound parts lymph vessels run along the fascia of the pectoral major muscle to the axillary region.  Some part of those vessels perforate that muscle and run to the inrfa and supraclavicular lymph nodes.  From the medial, inner part of the breast lymph vessels perforate the intercostal spaces and empty themselves into parasternal lymph nodes.  These are the only lymph vessels that pass by axillary lymph nodes (8).

Axillary lymph nodes, there are 30 to 40 of them.  They are divided into few groups: apical lymph nodes, central lymph nodes, lateral lymph nodes, pectoral lymph nodes and subscapular lymph nodes (figure 11) (9, 14).

Intercostal nerves innervate the breast.  Branches of the supraclavicular nerves also innervate superior part of the breast (8).

PHYSIOLOGY of the breast

The breasts are accessory glands of the generative systems.  They exist in the male but only in the rudimentary state.  Breasts secrete the milk enabling nutrition of the infant by hormonal feedback (1, 8).

In the female, estrogens cyclically stimulate growth of the breast.  But, complete development of the breast occurs during the pregnancy.

During the pregnancy, placenta secretes large amount of estrogen that induces the growth, division, elongation of the tubular duct system, nipple maturation and fat deposit.  Besides estrogen, at least four hormones have influence, permissive role in the control of milk formation: thyroxin, insulin, growth hormone and glucocoriticoids of the suprarenal gland. 

Also, under the influence of progesterone, lobules are increased, alveoli bud and alveolar cells get secretory characteristics.  Estrogen and progesterone also have a specific inhibitory effect on the milk production.

Prolactin, produced by pituitary gland, plays the critical role in the initiation and maintenance of lactation in the puerperium. Its concentration rises during pregnancy and at the end of pregnancy is 10 times higher than normal.

Furthermore, placenta produces large amount of the somatotropin that prepares the breast for milk production.

Until delivery, breasts produce small amount of colostrum that does not contain fat unlike regular milk.  After delivery, production of estrogen and progesterone decreases allowing lactogen effect of prolactin to be expressed.  Therefore, two or three days after delivery breasts start to produce high amount of milk.  Except prolactin, other hormones such as insulin, growth hormone and glucocoriticoids have an important role in the milk secretion due to their role in metabolisms of the amino acid, glucose, fat acid and calcium, which are needed for milk generation (figure 12).

 The level of the prolactin decreases after delivery on the regular level, but prolactin secretion is enhanced by stimulation of the breasts, such as the act of nursing (each nursing cause 10 times fold increment secretion of the prolactin that lasts for one hour).  That prolactin provides milk for a next nurse.  If a woman does not nurse or empty her breasts postpartum or hypothalamus or pituitary gland are impaired, lactation usually ceases in 1 to 2 weeks.

Milk is continuously secreted into alveoli of the breast.  Oxytocin causes contraction of the myoepithelial cells of the mammary alveoli, causing them to expel milk from the secretory tissue to the nipple.  Oxytocin is secreted at the same time with the prolactin, with the transmission of impulse along somatic nerves through spine to the hypothalamus. This process starts one minute after infant starts to suck.  Sometimes, even infant’s cry can induce oxytocin secretion.  Inhibition of secretion of the oxytocin is possible as a result of the psychogenic factors or generalized sympathetic stimulation.  Therefore, woman should have undisturbed puerperium to nurse (12, 15).

BREAST DISEASES

In the male, the breast is a rudimentary organ, relatively insensitive to endocrine influences.  On the other hand, in the female, the more complex breast structure and the extreme sensitivity to endocrine influences predispose this organ to a number of pathologic conditions.

All breast diseases can be divided into two groups: non-tumor and tumor disease.

NON -TUMOR BREAST DISEASES

1.        Developmental disorders: amastia (lack of breast), micromastia (little breast), macromastia (big breast), polymasita (extra breasts), athelia (nipple deficiency), microthelia (small nipple), polythelia (extra nipple).

2.        Functional disorders: galactorrhea (nonpuerperal or inappropriate lactation), bleeding breast, mastodinija (aching breast), extended period of the breast feeding, excessive milk production, small milk production and spontaneous leakage of the milk.

3.        Regressive changes: atrophy (“shrivelled” breasts), dystrophy (transformation of breast tissue to fat, mucine or calcified formation) fat necrosis (focal necrosis of fat tissues in the breast)

4.        Inflammatory changes: theilitis (nipple inflammation), areolitis (areola inflammation), intertrigo (eczema of the submammal sulkus), mastitis (inflammation of the milk gland, usually happens in the first two weeks after the delivery), apses (localized purulent inflammation), carbuncle (purulent skin and subcutaneous infections of the breast) and rarely tuberculosis, syphilis and actinomycosis.

5.        Dysplasia. The most ordinary and the most important is fibrocystic disease of the breast.  That is the most common breast alteration at all and the most common reason of coming to the physician.  It is also stated as predisposed factor of the breast cancer.  It is characterized by connective tissue proliferation (fibrosis) or milk gland cells proliferation (epithelial hyperplasia) or/and the formation of cysts (figure 13).  These changes are caused by the hormonal effects (estrogen, progesterone, prolactin) (16,17).

TUMOR BREAST DISEASES

1. Benign tumors. The most common is fibroadenoma (it is more common in younger female population) and papilloma 
(in the ducts which often causes bleeding, so even 50% of all bleeding discharge from the nipple is caused by that change).  The others are rather rare.  Those are: lipoma, haemangioma, neurinoma, chondroma.  Cysts also belong to this group.  The special type of rare breast tumor is phyllodes tumors (consisted of cystic formations, giving the gross leaf-like pattern) (4).

2. Malign tumors (breast cancer). For this topic, see chapter.