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Breast

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This article is about the human breast. For other mammals, see udder and mammary gland. For other uses, see Breast (disambiguation).
"Boobs" redirects here. For other uses, see boob (disambiguation).
Breast
Weibliche brust en.jpg
Morphology of breasts with the areola, nipple, and inframammary fold.
Details
Latin mamma (mammalis "of the breast")[1]
internal thoracic artery
internal thoracic vein
Identifiers
TA A16.0.02.001
FMA 9601
Anatomical terminology

The breast is one of two prominences found on the upper ventral region of the torso of male and female primates. In females it serves as the mammary gland, which produces and secretes milk and feeds infants.[2] Both males and females develop breasts from the same embryological tissues. At puberty, estrogens, in conjunction with growth hormone, causes breast development. Males do not develop pronounced or well-matured breasts because their bodies produce lower levels of estrogens and higher levels of androgens, namely testosterone, which suppress the effects of estrogens in developing breast tissue. The breasts of females are typically far more prominent than those of males.

Subcutaneous fat covers and envelops a network of ducts that converge to the nipple, and these tissues give the breast its size and shape. At the ends of the ducts are lobules, or clusters of alveoli, where milk is produced and stored in response to hormonal signals.[3] During pregnancy, the breast responds to a complex interaction of hormones, including estrogens, progesterone, and prolactin, that mediate the completion of its development, namely lobuloalveolar maturation, in preparation of lactation and breastfeeding. Upon childbirth, the alveoli are stimulated to produce and secrete milk for infants.

Along with their function in feeding infants, female breasts have social and sexual characteristics. Breasts have been featured in notable ancient and modern sculpture, art, and photography. Female breasts can figure prominently in a woman's perception of her body image and sexual attractiveness. A number of Western cultures associate breasts with sexuality and tend to regard bare breasts as immodest or indecent. Breasts and especially the nipples are an erogenous zone on women. Given the emphasis of some cultures on breast size and attractiveness, some women seek breast augmentation or other kinds of surgery to enlarge or reduce their breast size or to reverse sagging breasts.

Etymology

The English word breast derives from the Old English word brēost (breast, bosom) from Proto-Germanic breustam (breast), from the Proto-Indo-European base bhreus– (to swell, to sprout).[4] The breast spelling conforms to the Scottish and North English dialectal pronunciations.[5]

Anatomy

The Breast: cross-section scheme of the mammary gland.
1. Chest wall
2. Pectoralis muscles
3. Lobules
4. Nipple
5. Areola
6. Milk duct
7. Fatty tissue
8. Skin

In women, the breasts overlay the pectoralis major muscles and usually extend from the level of the second rib to the level of the sixth rib in the front of the human rib cage; thus, the breasts cover much of the chest area and the chest walls. At the front of the chest, the breast tissue can extend from the clavicle (collarbone) to the middle of the sternum (breastbone). At the sides of the chest, the breast tissue can extend into the axilla (armpit), and can reach as far to the back as the latissimus dorsi muscle, extending from the lower back to the humerus bone (the longest bone of the upper arm). As a mammary gland, the breast is composed of layers of different types of tissue, among which predominate two types, adipose tissue and glandular tissue, which effects the lactation functions of the breasts. [6]:115

Morphologically, the breast is a cone with the base at the chest wall, and the apex is at the nipple, the center of the nipple-areola complex. The superficial tissue layer (superficial fascia) is separated from the skin by 0.5–2.5 cm of subcutaneous fat (adipose tissue). The suspensory Cooper's ligaments are fibrous-tissue prolongations that radiate from the superficial fascia to the skin envelope. The female adult breast contains 14–18 irregular lactiferous lobes that converge at the nipple. Milk exits the breast through the nipple, which is surrounded by a pigmented area of skin called the areola. The size of the areola can vary widely among women. The areola contains modified sweat glands known as Montgomery's glands. These glands secrete oily fluid that lubricate and protect the nipple during breastfeeding.[7] Volatile compounds in these secretions may also serve as an olfactory stimulus for newborn appetite.[8]

The 2.0–4.5 mm milk ducts are immediately surrounded with dense connective tissue that support the glands. The glandular tissue of the breast is biochemically supported with estrogen. When a woman ceases menstruation and her body estrogen levels decrease, breast atrophy occurs – milk gland tissue atrophies, withers, and disappears, resulting in a breast composed of adipose tissue, superficial fascia, suspensory ligaments, and the skin envelope.[citation needed]

The dimensions and weight of the breast vary widely among women, ranging from approximately 500 to 1,000 grams (1.1 to 2.2 pounds) each. A small-to-medium-sized breast weighs 500 grams (1.1 pounds) or less and a large breast can weighs approximately 750 to 1,000 grams (1.7 to 2.2 pounds) or more. The tissue composition ratios of the breast also vary among women. Some women's breasts have varying proportions of glandular tissue than of adipose or connective tissues. The fat-to-connective-tissue ratio determines the density or firmness of the breast. During a woman's life, her breasts change size, shape, and weight due to hormonal bodily changes during puberty, fertility, pregnancy, breastfeeding, and menopause.[9][10]

Glandular structure

The breast is an apocrine gland that produces milk to feed an infant child; for which the nipple of the breast is surrounded by the areola (nipple-areola complex), the skin color of which varies from pink to dark brown, and has many sebaceous glands. The basic units of the breast are the terminal duct lobular units (TDLUs), which produce the fatty breast milk. They give the breast its offspring-feeding functions as a mammary gland. They are distributed throughout the body of the breast; approximately two-thirds of the lactiferous tissue is within 30 mm of the base of the nipple. The terminal lactiferous ducts drain the milk from TDLUs into 4–18 lactiferous ducts, which drain to the nipple; the milk-glands-to-fat ratio is 2:1 in a lactating woman, and 1:1 in a non-lactating woman. In addition to the milk glands, the breast also is composed of connective tissues (collagen, elastin), white fat, and the suspensory Cooper's ligaments. Sensation in the breast is provided by the peripheral nervous system innervation, by means of the front (anterior) and side (lateral) cutaneous branches of the fourth-, the fifth-, and the sixth intercostal nerves, while the T-4 nerve (Thoracic spinal nerve 4), which innervates the dermatomic area, supplies sensation to the nipple-areola complex.[11]

Lymphatic drainage

Approximately 75% of the lymph from the breast travels to the axillary lymph nodes on the same side of the body, whilst 25% of the lymph travels to the parasternal nodes (beside the sternum bone).[6]:116 A small amount of remaining lymph travels to the other breast, and to the abdominal lymph nodes. The axillary lymph nodes include the pectoral (chest), subscapular (under the scapula), and humeral (humerus-bone area) lymph-node groups, which drain to the central axillary lymph nodes and to the apical axillary lymph nodes. The lymphatic drainage of the breasts is especially relevant to oncology, because breast cancer is a cancer common to the mammary gland, and cancer cells can metastasize (break away) from a tumour and be dispersed to other parts of the body by means of the lymphatic system.

Shape and support

A pregnant woman's breasts

The morphologic variations in the size, shape, volume, tissue density, pectoral locale, and spacing of the breasts determine their natural shape, appearance, and position on a woman's chest. Breast size and other characteristics do not predict the fat-to-milk-gland ratio or the potential for the woman to nurse an infant child.[12] The size and the shape of the breasts are influenced by normal-life hormonal changes (thelarche, menstruation, pregnancy, menopause) and medical conditions (e.g. virginal breast hypertrophy).[13] The shape of the breasts is naturally determined by the support of the suspensory Cooper's ligaments, the underlying muscle and bone structures of the chest, and the skin envelope. The suspensory ligaments sustain the breast from the clavicle (collarbone) and the clavico-pectoral fascia (collarbone and chest), by traversing and encompassing the fat and milk-gland tissues, the breast is positioned, affixed to, and supported upon the chest wall, while its shape is established and maintained by the skin envelope.[citation needed] While it has been a common belief that breastfeeding causes breasts to sag,[14] researchers have found that a woman's breasts sag due to four key factors: cigarette smoking, the number of pregnancies, gravity, and weight gain and loss.[15]

The base of each breast is attached to the chest by the deep fascia over the pectoralis major muscles. The space between the breast and the pectoralis major muscle is called retromammary space and gives mobility to the breast. Some breasts are mounted high upon the chest wall, are of rounded shape, and project almost horizontally from the chest, which features are common to girls and women in the early stages of thelarchic development, the sprouting of the breasts. In the high-breast configuration, the dome-shaped and the cone-shaped breast is affixed to the chest at the base, and the weight is evenly distributed over the base area. In the low-breast configuration, a proportion of the breast weight is supported by the chest, against which rests the lower surface of the breast, thus is formed the inframammary fold (IMF). Because the base is deeply affixed to the chest, the weight of the breast is distributed over a greater area, and so reduces the weight-bearing strain upon the chest, shoulder, and back muscles that bear the weight of the bust.[citation needed]

The chest (thoracic cavity) progressively slopes outwards from the thoracic inlet (atop the breastbone) and above to the lowest ribs that support the breasts. The inframammary fold, where the lower portion of the breast meets the chest, is an anatomic feature created by the adherence of the breast skin and the underlying connective tissues of the chest; the IMF is the lower-most extent of the anatomic breast. In the course of thelarche, some girls develop breasts the lower skin-envelope of which touches the chest below the IMF, and some girls do not; both breast anatomies are statistically normal morphologic variations of the size and shape of women's breasts.[16]

Asymmetry

Up to 25% of women's breasts display a persistent, visible breast asymmetry,[17][18] which is defined as differing in size by at least one cup size. For about 5% to 10%[19] of women, their breasts are severely different, with the left breast being larger in 62% of cases.[19] This is due to the left breast's proximity to the heart, a greater number of arteries and veins, and a protective layer of fat surrounding the heart located beneath it.

The most common cause for asymmetric breast density is the common normal variant of asymmetrically distributed breast tissue. Minor asymmetry may be resolved by wearing a padded bra, but in severe cases of developmental breast deformity—commonly called "Amazon's Syndrome" by physicians—may require corrective surgery due to morphological alterations caused by variations in shape, volume, position of the breasts relative to the inframammary fold, the nipple-areola complex on the chest, or both.[20][21]

If a woman is uncomfortable with her breasts' asymmetry and the difference is relatively minor, she can minimize the difference with a corrective or padded bra or use gel bra inserts. If the difference is significant, this can indicate that the woman should consult a doctor to establish the cause. Breast asymmetry is related to several known risk factors for breast cancer,[22] but only 3% of mammograms of women with asymmetrical breasts result in a cancer diagnosis.[23] Types of breast asymmetry include bilateral asymmetric hypertrophy, unilateral hypertrophy with normal contralateral breast, unilateral hypertrophy with amastia or hypoplasia of the contralateral side, unilateral amastia or hypoplasia with normal contralateral breast, asymmetric bilateral hypoplasia, and unilateral mammary ptosis.[20]

Most surgeons will only perform an augmentation procedure to treat asymmetry if the woman's breasts differ by at least one cup size. Options include a minimally invasive procedure known as platelet injection fat transfer, which transfers fat cells from the woman's thighs to her smaller breast. More invasive procedures include reduction or augmentation mammoplasty, such as mastopexy, breast reduction plasty, or breast augmentation. Depending on the nature of the asymmetry, it may be necessary to operate on one or both breasts.[19][20]

Development

Overview

The Tanner Scale indicates the five development stages of the secondary sex characteristics (breasts and pubic hair) of girls and women.

The morphological structure of the human breast is identical in males and females until puberty. For a girl in puberty, during thelarche (the breast-development stage), the female sex hormones (principally estrogens) promote the sprouting, growth, and development of the breasts, in the course of which, as mammary glands, they grow in size and volume, and rest on her chest; these development stages of secondary sex characteristics (breasts, pubic hair, etc.) are illustrated in the five-stage Tanner Scale.[24]

During thelarche, the developing breasts sometimes are of unequal size, and usually the left breast is slightly larger; said condition of asymmetry is transitory and statistically normal to female physical and sexual development.[25] Moreover, breast development sometimes is abnormal, manifested either as overdevelopment (e.g., virginal breast hypertrophy, macromastia) or as underdevelopment (e.g., tuberous breast deformity, micromastia) in girls and women; and manifested in boys and men as gynecomastia (woman's breasts), the consequence of a biochemical imbalance between the normal levels of estrogen and testosterone in the male body.[26]

Approximately two years after the onset of puberty (a girl's first menstrual cycle), the hormone estrogen, in conjunction with growth hormone, stimulates the development and growth of the glandular, fat, and suspensory tissues that compose the breast. This continues for approximately four years until establishing the final shape of the breast (size, volume, density) when she is a woman of approximately 21 years of age.[12] Mammoplasia (breast enlargement) in girls begins at puberty, unlike all other primates in which breasts enlarge only during lactation.[7]

On the skin envelope of the breast, stretch marks may indicate the relative-size increments and decrements occurred during the life of the woman.

The breasts are principally composed of adipose, glandular and connective tissues.[27] Because these tissues have hormone receptors,[27][28] their sizes and volumes fluctuate according to the hormonal changes particular to thelarche (sprouting of breasts), menstruation (egg production), pregnancy (reproduction), lactation (feeding of offspring), and menopause (end of menstruation).

During the menstrual cycle, the breasts are enlarged by premenstrual water retention and temporary growth.[29] During pregnancy, the breasts become enlarged and denser (firmer) because of the prolactin-caused organ hypertrophy, which begins the production of breast milk, increases the size of the nipples, and darkens the skin color of the nipple-areola complex. These changes continue during the lactation and the breastfeeding periods. Afterwards, the breasts generally revert to their pre-pregnancy size, shape, and volume, yet might show stretch marks.[citation needed]

At menopause, breast atrophy occurs – the breasts can decrease in size when the levels of circulating estrogen decline, followed by the withering of the adipose tissue and the milk glands. Additional to such natural biochemical stimuli, the breasts can become enlarged consequent to an adverse side effect of combined oral contraceptive pills; and the size of the breasts can also increase and decrease in response to the body weight fluctuations of the woman. Moreover, the physical changes occurred to the breasts often are recorded in the stretch marks of the skin envelope; they can serve as historical indicators of the increments and the decrements of the size and the volume of a woman's breasts throughout the course of her life.[citation needed]

Biochemistry

Hormones

The master regulators of breast development are the steroid hormones, estrogen and progesterone, growth hormone (GH), mostly via its secretory product, insulin-like growth factor 1 (IGF-1), and prolactin.[30] These regulators induce the expression of growth factors, such as amphiregulin, epidermal growth factor (EGF), IGF-1, and fibroblast growth factor (FGF), which in turn have specific roles in breast growth and maturation.[30]

At puberty, gonadotropin-releasing hormone (GnRH) begins to be secreted, in a pulsatile manner, from the hypothalamus.[31][32] GnRH, in turn, induces the secretion of the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), from the pituitary gland.[31][32] These hormones travel to the ovaries through the bloodstream and cause estrogen and progesterone to be produced by them and released into the body in fluctuating amounts with each menstrual cycle.[31][32] Growth hormone (GH), which is secreted from the pituitary gland, and insulin-like growth factor 1 (IGF-1), which is produced in the body in response to GH, are growth-mediating hormones.[33] During prenatal development, infancy, and childhood, GH and IGF-1 levels are low, but progressively increase and reach a peak at puberty,[34] with a 1.5- to 3-fold increase in pulsatile GH secretion and a 3-fold or greater increase in serum IGF-1 levels being capable of occurring at this time.[35] In late adolescence and early adulthood, GH and IGF-1 levels significantly decrease,[36] and continue to decrease throughout the rest of life.[34] It has been found that both estrogen and GH are essential for breast development at puberty – in the absence of either, no development will take place.[37][38] Moreover, most of the role of GH in breast development has been found to be mediated by its induction of IGF-1 production and secretion, as IGF-1 administration rescues breast development in the absence of GH.[38] GH induction of IGF-1 production and secretion occurs in almost all types of tissue in the body, but especially in the liver, which is the source of approximately 80% of circulating IGF-1,[39] as well as locally in the breasts.[34][40] Although IGF-1 is responsible for most of the role of GH in mediating breast development, GH itself has been found to play a direct, augmenting role as well, as it increases estrogen receptor (ER) expression in breast stromal (connective) tissue, while IGF-1, in contrast, has been found to not do this.[41][42] In addition to estrogen and GH/IGF-1 both being essential for pubertal breast development, they are synergistic in bringing it about.[37][38][43]

Development of the breasts during the prenatal stage of life is independent of biological sex and sex hormones.[44] During embryonic development, the breast buds, in which networks of tubules are formed, are generated from the ectoderm.[45] These rudimentary tubules will eventually become the matured lactiferous (milk) ducts, which connect the lobules (milk "containers") of the breast, grape-like clusters of alveoli, to the nipples.[46] Until puberty, the tubule networks of the breast buds remain rudimentary and quiescent,[30] and the male and female breast do not show any differences.[44] During puberty in females, estrogen, in conjunction with GH/IGF-1, through activation of ERα specifically (and notably not ERβ or GPER),[47][48] causes growth of and transformation of the tubules into the matured ductal system of the breasts.[44][45][49] Under the influence of estrogen, the ducts sprout and elongate, and terminal end buds (TEBs), bulbous structures at the tips of the ducts, penetrate into the fat pad and branch as the ducts elongate.[44][45][49] This continues until a tree-like network of branched ducts that is embedded into and fills the entire fat pad of the breast is formed.[30][44][45][49] In addition to its role in mediating ductal development, estrogen causes stromal tissue to grow and adipose (fat) tissue to accumulate,[44][45] as well as the nipple-areolar complex to increase in size.[50]

Progesterone, in conjunction with GH/IGF-1 similarly to estrogen, affects the development of the breasts during puberty and thereafter as well.[44][45][49] To a lesser extent than estrogen, progesterone contributes to ductal development at this time, as evidenced by the findings that progesterone receptor (PR) knockout mice or mice treated with the PR antagonist mifepristone show delayed (albeit eventually normal, due to estrogen acting on its own) ductal growth during puberty and by the fact that progesterone has been found to induce ductal growth on its own in the mouse mammary gland mainly via the induction of the expression of amphiregulin, the same growth factor that estrogen primarily induces to mediate its actions on ductal development.[51] In addition, progesterone produces modest lobuloalveolar development (alveolar bud formation or ductal sidebranching) starting at puberty,[44][49] specifically through activation of PRB (and notably not PRA),[52] with growth and regression of the alveoli occurring to some degree with each menstrual cycle.[44][45] However, only rudimentary alveoli develop in response to pre-pregnancy levels of progesterone and estrogen, and lobuloalveolar development will remain at this stage until pregnancy occurs, if it does.[45] In addition to GH/IGF-1, estrogen is required for progesterone to affect the breasts,[44][49] as estrogen primes the breasts by inducing the expression of the progesterone receptor (PR) in breast epithelial tissue.[52] In contrast to the case of the PR, ER expression in the breast is stable and differs relatively little in the contexts of reproductive status, stage of the menstrual cycle, or exogenous hormonal therapy.[52]

During pregnancy, pronounced breast growth and maturation occurs in preparation of lactation and breastfeeding.[44][53][54] Estrogen and progesterone levels increase dramatically,[44] reaching levels by late pregnancy that are several hundred-fold higher than usual menstrual cycle levels.[55] Estrogen and progesterone cause the secretion of high levels of prolactin from the anterior pituitary,[56][57] which reach levels as high as 20 times greater than normal menstrual cycle levels.[55] IGF-1 and IGF-2 levels also increase dramatically during pregnancy, due to secretion of placental growth hormone (PGH).[58] Further ductal development, by estrogen, again in conjunction with GH/IGF-1, occurs during pregnancy.[45][46] In addition, the concert of estrogen, progesterone (again specifically through PRB),[52] prolactin, and other lactogens such as human placental lactogen (hPL) and PGH, in conjunction with GH/IGF-1, as well as insulin-like growth factor 2 (IGF-2),[59][60] acting together, mediate the completion of lobuloalveolar development of the breasts during pregnancy.[45][46][61][62] Both PR and prolactin receptor (PRLR) knockout mice fail to show lobuloalveolar development, and progesterone and prolactin have been found to be synergistic in mediating growth of alveoli, demonstrating the essential role of both of these hormones in this aspect of breast development.[63][64] Growth hormone receptor (GHR) knockout mice also show greatly impaired lobuloalveolar development.[65] In addition to their role in lobuloalveolar growth, prolactin and hPL act to increase the size of the nipple-areolar complex during pregnancy.[66] By the end of the fourth month of pregnancy, at which time lobuloalveolar maturation is complete, the breasts are fully prepared for lactation and breastfeeding.[54]

Insulin, glucocorticoids such as cortisol (and by extension adrenocorticotropic hormone (ACTH)), and thyroid hormones such as thyroxine (and by extension thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone (TRH)) also play permissive but less well-understood/poorly-characterized roles in breast development during both puberty and pregnancy, and are required for full functional development.[67][68][69][70] Leptin has also been found to be an important factor in mammary gland development, and has been found to promote mammary epithelial cell proliferation.[71][31]

In contrast to the female-associated sex hormones, estrogen and progesterone, the male-associated sex hormones, the androgens, such as testosterone and dihydrotestosterone (DHT), powerfully suppress the action of estrogen in the breasts.[61][70][72][73] At least one way that they do this is by reducing the expression of the estrogen receptor in breast tissue.[72][73][74] In the absence of androgenic activity, such as in women with complete androgen insensitivity syndrome (CAIS), modest levels of estrogen (50 pg/mL) are capable of mediating significant breast development, with CAIS women showing breast volumes that are even above-average.[61] The combination of much higher levels of androgens (about 10-fold higher) and much lower levels of estrogen (about 10-fold less),[75] due to the ovaries in females producing high amounts of estrogens but low amounts of androgens and the testes in males producing high amounts of androgens but low amounts of estrogens,[76] are why males generally do not grow prominent or well-developed breasts relative to females.[70][77]

Calcitriol, the hormonally active form of vitamin D, acting through the vitamin D receptor (VDR), has, like the androgens, been reported to be a negative regulator of breast development in mice, for instance, during puberty.[65] VDR knockout mice show more extensive ductal development relative to wild-type mice,[78] as well as precocious mammary gland development.[79] In addition, VDR knockout has also been shown to result in increased responsiveness of mouse mammary gland tissue to estrogen and progesterone, which was represented by increased cell growth in response to these hormones.[78] Conversely however, it has been found that VDR knockout mice show reduced ductal differentiation, represented by an increased number of undifferentiated TEBs,[80] and this finding has been interpreted as indicating that vitamin D may be essential for lobuloalveolar development.[64] As such, calcitriol, via the VDR, may be a negative regulator of ductal development but a positive regulator of lobuloalveolar development in the mammary gland.[81]

A possible mechanism of the negative regulatory effects of the VDR on breast development may be indicated by a study of vitamin D3 supplementation in women which found that vitamin D3 suppresses cyclooxygenase-2 (COX-2) expression in the breast, and by doing so, reduces and increases, respectively, the levels of prostaglandin E2 (PGE2) and Transforming growth factor β2 (TGF-β2), a known inhibitory factor in breast development.[82] Moreover, suppression of PGE2 in breast tissue is relevant because, via activation of prostaglandin EP receptors, PGE2 potently induces amphiregulin expression in breast tissue, and activation of the EGFR by amphiregulin increases COX-2 expression in breast tissue, in turn resulting in more PGE2, and thus, a self-perpetuating, synergistic cycle of growth amplification due to COX-2 appears to potentially be present in normal breast tissue.[83][84] Accordingly, overexpression of COX-2 in mammary gland tissue produces mammary gland hyperplasia as well as precocious mammary gland development in female mice, mirroring the phenotype of VDR knockout mice, and demonstrating a strong stimulatory effect of COX-2, which is downregulated by VDR activation, on the growth of the mammary glands.[83][84] Also in accordance, COX-2 activity in the breasts has been found to be positively associated with breast volume in women.[85]

Growth factors

Estrogen, progesterone, and prolactin, as well as GH/IGF-1, produce their effects on breast development by modulating the local expression in breast tissue of an assortment of autocrine and paracrine growth factors,[49][68][86][87][88] including IGF-1, IGF-2, amphiregulin,[89] EGF, FGF, hepatocyte growth factor (HGF),[90] tumor necrosis factor α (TNF-α), tumor necrosis factor β (TNF-β), transforming growth factor α (TGF-α),[91] transforming growth factor β (TGF-β),[92] heregulin,[93] Wnt,[64] RANKL,[64] and leukemia inhibitory factor (LIF).[64] These factors regulate cellular growth, proliferation, and differentiation via activation of intracellular signaling cascades that control cell function, such as Erk, Akt, JNK, and Jak/Stat.[39][94][95][96]

Based on research with epidermal growth factor receptor (EGFR) knockout mice, the EGFR, which is the molecular target of EGF, TGF-α, amphiregulin, and heregulin, has, similarly to the insulin-like growth factor-1 receptor (IGF-1R),[30] been found to be essential for mammary gland development.[97] Estrogen and progesterone mediate ductal development mainly through induction of amphiregulin expression, and thus downstream EGFR activation.[51][89][94][98][99] Accordingly, ERα, amphiregulin, and EGFR knockout mice copy each other phenotypically in regards to their effects on ductal development.[98] Also in accordance, treatment of mice with amphiregulin or other EGFR ligands like TGF-α or heregulin induces ductal and lobuloalveolar development in the mouse mammary gland, actions that occur even in the absence of estrogen and progesterone.[93][100] As both the IGF-1R and the EGFR are independently essential for mammary gland development, and as combined application of IGF-1 and EGF, through their respective receptors, has been found to synergistically stimulate the growth of human breast epithelial cells, these growth factor systems appear to work together in mediating breast development.[101][102][103]

Breast size

It has been reported that Asian women, on average, tend to have smaller breasts than Caucasian women.[104]

Through genome-wide association studies (GWAS), a variety of genetic polymorphisms have been linked to breast size.[105] Some of these include rs7816345 near ZNF703 (zinc finger protein 703), rs4849887 and rs17625845 flanking INHBB (inhibin βB), rs12173570 near ESR1 (ERα), rs7089814 in ZNF365 (zinc finger protein 365), rs12371778 near PTHLH (parathyroid hormone-like hormone), and rs62314947 near AREG (amphiregulin),[105] as well as rs10086016 at 8p11.23 (which is in complete linkage disequilibrium with rs7816345) and rs5995871 at 22q13 (contains the MKL1 gene, which has been found to modulate the transcriptional activity of ERα).[104] Many of these polymorphisms are also associated with the risk of developing breast cancer, revealing a potential positive association between breast size and breast cancer risk.[104][105] However, conversely, some polymorphisms show a negative association between breast size and breast cancer risk.[104] In any case, a meta-analysis concluded that breast size and risk of breast cancer are indeed importantly related.[106]

Circulating IGF-1 levels are positively associated with breast volume in women.[107] In addition, the absence of the common 19-repeat allele in the IGF1 gene is also positively associated with breast volume in women, as well as with high IGF-1 levels during oral contraceptive use and with lessening of the normal age-associated decline in circulating IGF-1 concentrations in women.[107] There is great variation in the prevalence of the IGF1 19-repeat allele between ethnic groups, and its absence has been reported to be highest among African-American women.[107]

Genetic variations in the androgen receptor (AR) have been linked to both breast volume (as well as body mass index) and breast cancer aggressiveness.[108]

Cyclooxygenase-2 (COX-2) expression has been positively associated with breast volume and inflammation in breast tissue (which is also positively associated with breast volume), as well as with breast cancer risk and prognosis.[85]

Women with complete androgen insensitivity syndrome (CAIS), who are completely insensitive to the AR-mediated actions of androgens, are, as a group, above-average in regards to breast size, which is in spite of the fact that they simultaneously have relatively low levels of estrogen, demonstrating the powerful suppressant effect of androgens on estrogen-mediated breast development.[61]

Elevated levels of HGF and, to a lesser extent, IGF-1 (by 5.4-fold and 1.8-fold, respectively), in breast stromal tissue, have been found in macromastia, a very rare condition of extremely and excessively large breast size.[109] Exposure of macromastic breast stromal tissue to non-macromastic breast epithelial tissue was found to cause increased alveolar morphogenesis and epithelial proliferation in the latter.[109] A neutralizing antibody for HGF, but not for IGF-1 or EGF, was found to attenuate the proliferative activity of macromastic breast stromal cells, potentially directly implicating HGF in the breast growth and enlargement seen in macromastia.[109] Also, a GWAS has highly implicated HGF and its receptor, c-Met, in breast cancer aggressiveness.[110]

Aromatase excess syndrome (AES), an extremely rare condition characterized by marked hyperestrogenism, is associated with precocious breast development and macromastia in females and similarly precocious gynecomastia (women's breasts) in males.[111][112][113]

Aging

Main article: Ptosis (breasts)
The seven stages of breast ptosis.

Breast ptosis, or sagging of the breasts, is a normal consequence of aging[114] where the breast tissue droops lower on the chest and the nipple points downward.[115] Researchers have found that ptosis is influenced by several key factors: greater age, higher body mass index, larger bra cup size, history of significant weight loss (>50 lbs), number of pregnancies, and history of cigarette smoking.[15][116][117] It is not caused, as commonly believed by many women and medical practitioners, by breastfeeding.[14]

Plastic surgeons categorize ptosis by evaluating the position of the nipple relative to the inframammary crease (where the underside of the breast meets the chest wall). This is determined by measuring from the center of the nipple to the sternal notch (at the top of the breast bone) to gauge how far the nipple has fallen. The standard anthropometric measurement for young women is 21 centimetres (8.3 in). This measurement is used to assess both breast ptosis and breast symmetry. The surgeon will assess the breast's angle of projection. The apex of the breast, which includes the nipple, can have a flat angle of projection (180 degrees) or acute angle of projection (greater than 180 degrees). The apex rarely has an angle greater than 60 degrees. The angle of the breast apex is partly determined by the tautness of the suspensory Cooper's ligaments. For example, when a woman lies on her back, the angle of the breast apex becomes a flat, obtuse angle (less than 180 degrees) while the base-to-length ratio of the breast ranges from 0.5 to 1.0.[114]

Physiology

Main article: Breastfeeding
The functional breast nourishing an infant girl.

The primary function of the breasts – as mammary glands – is the feeding and the nourishing of an infant child with breast milk during the maternal lactation period. The round shape of the breast helps to limit the loss of maternal body heat, because milk production depends upon a higher-temperature environment for the proper, milk-production function of the mammary gland tissues, the lactiferous ducts. Regarding the shape of the breast, the study The Evolution of the Human Beast (2001) proposed that the rounded shape of a woman's breast evolved to prevent the sucking infant offspring from suffocating while feeding at the teat; that is, because of the human infant's small jaw, which did not project from the face to reach the nipple, he or she might block the nostrils against the mother's breast if it were of a flatter form (cf. chimpanzee); theoretically, as the human jaw receded into the face, the woman's body compensated with round breasts.[118]

In a woman, the condition of lactation unrelated to pregnancy can occur as galactorrhea (spontaneous milk flow), and because of the adverse effects of drugs (e.g. antipsychotic medications), of extreme physical stress, and of endocrine disorders. In a newborn infant, the capability of lactation is consequence of the mother's circulating hormones (prolactin, oxytocin, etc.) in his or her blood stream, which were introduced by the shared circulatory system of the placenta. In men, the mammary glands are also present in the body, but normally remain undeveloped because of the hormone testosterone, however, when male lactation occurs, it is considered a pathological symptom of a disorder of the pituitary gland.

Lactation

Upon childbirth, estrogen and progesterone rapidly drop to very low levels, with progesterone levels being undetectable, while prolactin levels remain elevated.[44][53] As estrogen and progesterone block prolactin-induced lactogenesis, by suppressing prolactin receptor (PRLR) expression in breast tissue, specifically, their sudden absence results in the commencement of milk production and lactation by prolactin.[44][53] Expression of the PRLR in breast tissue may increase by as much as 20-fold when estrogen and progesterone levels drop upon childbirth.[44] With suckling from the infant, prolactin and oxytocin are secreted and mediate milk production and letdown, respectively.[44][45][53] Prolactin suppresses the secretion of LH and FSH, which in turn results in continued low levels of estrogen and progesterone, and temporary amenorrhea (absence of menstrual cycles) occurs.[53] In the absence of regular, episodic suckling, which keeps prolactin concentrations high, levels of prolactin will quickly drop, the menstrual cycle will resume and hence normal estrogen and progesterone levels will return, and lactation will permanently stop (that is, until next childbirth, or relactation (induced lactation) with a galactogogue, occurs).[53]

Clinical significance

Main article: Breast disease

The breast is susceptible to numerous benign and malignant conditions. The most frequent benign conditions are puerperal mastitis, fibrocystic breast changes and mastalgia. Breast cancer is one of the leading causes of death among women.

Society and culture

Art history

A Cretan Snake Goddess from the Minoan Civilization, c. 1600 BC.

In European pre-historic societies, sculptures of female figures with pronounced or highly exaggerated breasts were common. A typical example is the so-called Venus of Willendorf, one of many Paleolithic Venus figurines with ample hips and bosom. Artifacts such as bowls, rock carvings and sacred statues with breasts have been recorded from 15,000 BC up to late antiquity all across Europe, North Africa and the Middle East. Many female deities representing love and fertility were associated with breasts and breast milk. Figures of the Phoenician goddess Astarte were represented as pillars studded with breasts. Isis, an Egyptian goddess who represented, among many other things, ideal motherhood, was often portrayed as suckling pharaohs, thereby confirming their divine status as rulers. Even certain male deities representing regeneration and fertility were occasionally depicted with breast-like appendices, such as the river god Hapy who was considered to be responsible for the annual overflowing of the Nile. Female breasts were also prominent in the Minoan civilization in the form of the famous Snake Goddess statuettes. In Ancient Greece there were several cults worshipping the "Kourotrophos", the suckling mother, represented by goddesses such as Gaia, Hera and Artemis. The worship of deities symbolized by the female breast in Greece became less common during the first millennium. The popular adoration of female goddesses decreased significantly during the rise of the Greek city states, a legacy which was passed on to the later Roman Empire.[119]

During the middle of the first millennium BC, Greek culture experienced a gradual change in the perception of female breasts. Women in art were covered in clothing from the neck down, including female goddesses like Athena, the patron of Athens who represented heroic endeavor. There were exceptions: Aphrodite, the goddess of love, was more frequently portrayed fully nude, though in postures that were intended to portray shyness or modesty, a portrayal that has been compared to modern pin ups by historian Marilyn Yalom.[120] Although nude men were depicted standing upright, most depictions of female nudity in Greek art occurred "usually with drapery near at hand and with a forward-bending, self-protecting posture".[121] A popular legend at the time was of the Amazons, a tribe of fierce female warriors who socialized with men only for procreation and even removed one breast to become better warriors (the idea being that the right breast would interfere with the operation of a bow and arrow). The legend was a popular motif in art during Greek and Roman antiquity and served as an antithetical cautionary tale.

Body image

Top: conventional mastectomy. Bottom: Skin sparing mastectomy and latissimus dorsi myocutaneous flap reconstruction, prior to nipple reconstruction and tattooing.
Pre-operative (left) and post-operative (right) aspects of cosmetic surgery procedures: reduction mammoplasty (top), breast lift (center), breast augmentation with breast implants (bottom).

Many women regard their breasts as important to their sexual attractiveness, as a sign of femininity that is important to their sense of self. Due to this, when a woman considers her breasts deficient in some respect, she might choose to undergo a plastic surgery procedure to enhance them, either to have them augmented or to have them reduced, or to have them reconstructed if she suffered a deformative disease, such as breast cancer.[122] After mastectomy, the reconstruction of the breast or breasts is done with breast implants or autologous tissue transfer, using fat and tissues from the abdomen, which is performed with a TRAM flap or with a back (latissiumus muscle flap). Breast reduction surgery is a procedure that involves removing excess breast tissue, fat, and skin, and the repositioning of the nipple-areola complex.

Cosmetic improvement procedures include breast lift (mastopexy), breast augmentation with implants, and combination procedures; the two types of available breast implants are models filled with silicone gel, and models filled with saline solution. These types of breast surgery can also repair inverted nipples by releasing milk duct tissues that have become tethered. Furthermore, in the case of the obese woman, a breast lift (mastopexy) procedure, with or without a breast volume reduction, can be part of an upper-body lift and contouring for the woman who has undergone massive body weight loss.[citation needed]

Surgery of the breast presents the health risk of interfering with the ability to breast-feed an infant child, and might include consequences such as altered sensation in the nipple-areola complex, interference with mammography (breast x-rays images) when there are breast implants present in the breasts. Regarding breastfeeding capability after breast reduction surgery, studies reported that women who underwent breast reduction can retain the ability to nurse an infant child, when compared to women in a control group who underwent breast surgery using a modern pedicle surgical technique.[123][124][125][126][127][128][129] Plastic surgery organizations generally discourage elective cosmetic breast augmentation surgery for teen-aged girls, because, at that age, the volume of the breast tissues (milk glands and fat) can continue to grow as the girl matures to womanhood. Breast reduction surgery for teen-aged girls, however, is a matter handled according to the particulars of the case of hypoplasia. (see: breast hypertrophy.)

Other means of breast enlargement also exist, such as hormonal breast enhancement.[130][131]

Clothing

As is customary in her culture, a bare-breasted Himba woman of northern Namibia wears a traditional headdress and skirt.

Because breasts are mostly fatty tissue, their shape can within limits be molded by clothing, such as foundation garments. Bras are commonly worn by about 90% of Western women,[132][133][134] and are often worn for support.[135] The social norm in most Western cultures is to cover breasts in public, though the extent of coverage varies depending on the social context. Some religions ascribe a special status to the female breast, either in formal teachings or through symbolism.[citation needed] Islam forbids women from exposing their breasts in public.

Many cultures associate breasts with sexuality and tend to regard bare breasts as immodest or indecent. In some cultures, like the Himba in northern Namibia, bare-breasted women are normal, while a thigh is highly sexualised and not exposed in public. In a few Western countries female toplessness at a beach is acceptable, although it may not be acceptable in the town center. In some areas, exposing a woman's breasts applies only to the exposure of nipples.[citation needed]

In the United States, women who breast-feed in public can receive negative attention. There have been instances where women have been asked to leave public venues. In New York, the topfreedom equality movement helped to bring a case, People v. Santorelli (1992), to the New York State Court of Appeals. They ruled that New York's indecent exposure laws did not apply to a bare-breasted woman. Other (gender equality) efforts succeeded in most of Canada in the 1990s. Bare-breasted women are legal and culturally acceptable at public beaches in Australia and much of Europe.[citation needed]

Sexual characteristic

In some cultures, breasts play a role in human sexual activity. Breasts and especially the nipples are among the various human erogenous zones. They are sensitive to the touch as they have many nerve endings; and it is common to press or massage them with hands or orally before or during sexual activity. Some women can achieve an orgasm from such activities. Research has suggested that the sensations are genital orgasms caused by nipple stimulation, and may also be directly linked to "the genital area of the brain".[136][137] Sensation from the nipples travels to the same part of the brain as sensations from the vagina, clitoris and cervix. Nipple stimulation may trigger uterine contractions, which then produce a sensation in the genital area of the brain.[137] In the ancient Indian work the Kama Sutra, light scratching of the breasts with nails and biting with teeth are considered erotic.[138] During sexual arousal, breast size increases, venous patterns across the breasts become more visible, and nipples harden. Compared to other primates, human breasts are proportionately large throughout adult females' lives. Some writers have suggested that they may have evolved as a visual signal of sexual maturity and fertility.[139]

Many people regard the female human body, of which breasts are an important aspect, to be aesthetically pleasing, as well as erotic. Research conducted at the Victoria University of Wellington showed that breasts are often the first thing men look at, and for a longer time than other body parts.[140] The writers of the study had initially speculated that the reason for this is due to endocrinology with larger breasts indicating higher levels of estrogen and a sign of greater fertility,[140][141] but the researchers said that "Men may be looking more often at the breasts because they are simply aesthetically pleasing, regardless of the size."[140]

Many people regard bare female breasts to be erotic, and they can elicit heightened sexual desires in men in many cultures. Some people show a sexual interest in female breasts distinct from that of the person, which may be regarded as a breast fetish.[142] While U.S. culture prefers breasts that are youthful and upright, some cultures venerate women with drooping breasts, indicating mothering and the wisdom of experience.[143]

Anthropomorphic geography

Main article: Breast-shaped hill

There are many mountains named after the breast because they resemble it in appearance and so are objects of religious and ancestral veneration as a fertility symbol and of well-being. In Asia, there was "Breast Mountain", which had a cave where the Buddhist monk Bodhidharma (Da Mo) spent much time in meditation.[144] Other such breast mountains are Mount Elgon on the Uganda-Kenya border, Beinn Chìochan and the Maiden Paps in Scotland, the "Bundok ng Susong Dalaga" (Maiden's breast mountains) in Talim Island, Philippines, the twin hills known as the Paps of Anu (Dá Chích Anann or "the breasts of Anu"), near Killarney in Ireland, the 2,086 m high Tetica de Bacares or "La Tetica" in the Sierra de Los Filabres, Spain, and Khao Nom Sao in Thailand, Cerro Las Tetas in Puerto Rico and the Breasts of Aphrodite in Mykonos, among many others. In the United States, the Teton Range is named after the French word for "breast".[145]

Symbolism

In Christian iconography, some works of art depict women with their breasts in their hands or on a platter, signifying that they died as a martyr by having their breasts severed; one example of this is Saint Agatha of Sicily.[citation needed]

See also

References

Notes
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Bibliography

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