Hemorrhoid
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Hemorrhoid
Hemorrhoids
Classification and external resources
Schematic demonstrating the anatomy of hemorrhoids.
ICD-10
I84.
ICD-9
455
DiseasesDB
10036
MedlinePlus
000292
eMedicine
med/2821 emerg/242
MeSH
D006484
Hemorrhoids (US English) or haemorrhoids (Commonwealth English), also known as piles and "Tum-Bum" are part of the normal human anatomy of the anal canal. They become pathological when swollen or inflamed. In their physiological state they act as cushions composed of arterio-venous channels and connective tissue that aid the passage of stool. The symptoms of pathological hemorrhoids depend on the type present. Internal hemorrhoids usually present with painless rectal bleeding while external hemorrhoids present with pain in the area of the anus.
Recommended treatment consists of increasing fiber intake, oral fluids to maintain hydration, NSAID analgesics, sitz baths, and rest. Surgery is reserved for those who fail to improve following these measures.
Contents
• 1 Signs and symptoms
• 2 Causes
• 3 Pathophysiology
• 4 Prevention
• 5 Diagnosis
o 5.1 Differential
• 6 Treatments
o 6.1 Procedures
• 7 Epidemiology
• 8 Notable cases
• 9 References
Signs and symptoms
Classical appearance of an external hemorrhoid.
Hemorrhoids are usually benign. In most cases, symptoms will resolve within a few days. External hemorrhoids are painful while internal hemorrhoids usually are not.
The most common symptom of internal hemorrhoids is bright red blood covering the stool, a condition known as hematochezia, on toilet paper, or in the toilet bowl. They may protrude through the anus. Symptoms of external hemorrhoids include painful swelling or lump around the anus.
Causes
A number of factors may lead to the formations of hemorrhoids including irregular bowel habits (constipation or diarrhea), exercise, gravity, nutrition (low-fiber diet), increased intra-abdominal pressure (prolonged straining), pregnancy, genetics, absence of valves within the hemorrhoidal veins, and aging.
Other factors that can increase the rectal vein pressure resulting in hemorrhoids include obesity, and sitting for long periods of time.
During pregnancy, pressure from the fetus on the abdomen and hormonal changes cause the hemorrhoidal vessels to enlarge. Delivery also leads to increase intra abdominal pressures. Surgical treatment is rarely needed as symptoms usually resolve post delivery.
Pathophysiology
This section requires expansion.
Hemorrhoid cushions are a part of normal human anatomy and only become a pathological disease when they experience abnormal changes. There are three cushions present in the normal anal canal.
Prevention
The best way to prevent hemorrhoids is to keep stools soft so they pass easily, thus decreasing pressure and straining, and to empty bowels as soon as possible after the urge occurs. Exercise, including walking, and increased fiber in the diet help reduce constipation and straining by producing stools that are softer and easier to pass. Spending less time attempting to defecate and avoiding reading while on the toilet have been recommended.
Diagnosis
Endoscopic image of internal hemorrhoids seen on retroflexion of the flexible sigmoidoscope at the ano-rectal junction
A visual examination of the anus and surrounding area may be able to diagnose external or prolapsed hemorrhoids. A rectal exam may be performed to detect possible rectal tumors, polyps, an enlarged prostate, or abscesses. This examination may not be possible without appropriate sedation due to pain.
Visual confirmation of internal hemorrhoids is via anoscopy. This device is basically a hollow tube with a light attached at one end that allows one to see the internal hemorrhoids, as well possible polyps in the rectum.
Differential
Many anorectal problems, including fissures, fistulae, abscesses, colorectal cancer, rectal varices and itching,diverticulosis,polyps have similar symptoms and may be incorrectly referred to as hemorrhoids.
Treatments
Conservative treatment typically consists of increasing dietary fiber, oral fluids to maintain hydration, non-steroidal anti-inflammatory drugs (NSAID)s,
sitz baths, and rest. Increased fiber intake has been shown to improve outcomes and may be achieved by dietary alterations or the consumption of fibre supplements .
While many topical agents and suppositories are available for the treatment of hemorrhoids there is little evidence to support their use. Preparation H may improve local symptoms but does not improve the underlying disorder and long term use is discouraged due to local irritation of the skin.
Procedures
• Rubber band ligation is a procedure in which elastic bands are applied onto an internal hemorrhoid at least 1 cm above the dentate line to cut off its blood supply. Within 5–7 days, the withered hemorrhoid falls off. If the band is placed too close to the dentate line intense pain results immediately afterwards.Cure rate has been found to be about 87%.
• Sclerotherapy involves the injection of a sclerosing agent (such as phenol) into the hemorrhoid. This causes the vein walls to collapse and the hemorrhoids to shrivel up. The success rate at four years is 70%.
• A number of cautery methods have been shown to be effective for hemorrhoids. This can be done using electrocautery, infrared radiation, or cryosurgery. A number of surgical techniques may be used if conservative medical management fails. All are associated with some degree of complications including urinary retention, due to the close proximity to the rectum of the nerves that supply the bladder, bleeding, infection, and anal strictures.
• Hemorrhoidectomy is a surgical excision of the hemorrhoid used primary only in severe cases. It is associated with significant post operative pain and usually requires 2–4 weeks for recovery.
• Doppler guided transanal hemorrhoidal dearterialization is a minimally invasive treatment. Consiosts in ligation of the six branches of the superior rectal artery, the cause of arterial hyperinflux and therefore of swelling and bleeding of the haemorrhoidal plexus, which are localised and ligated high in the rectal canal. It is not at all invasive as no tissue is cut or removed in the anal-rectal canal. Given its non-invasiveness, no significant complications can occur. The method can be repeated and does not prevent other operations on the anal-rectal channel from being carried out as full restitutio ad integrum occurs within three months from the operation, that is, the anal-rectal canal regains its normal anatomy as though it had never been operated on at all.
• Stapled hemorrhoidectomy is a procedure that involves resection of soft tissue proximal to the dentate line, disrupting the blood flow to the hemorrhoids. It is generally less painful than complete removal of hemorrhoids and was associated with faster healing compare to a hemorrhoidectomy.
Epidemiology
Symptomatic hemorrhoids affect at least 50% of the American population at some time during their lives, with around 5% of the population suffering at any given time, and both sexes experiencing the same incidence of the condition. They are more common in Caucasians
Heart
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Heart
Liver Function
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Liver function
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion. The liver is necessary for survival; there is currently no way to compensate for the absence of liver function.
This organ plays a major role in metabolism and has a number of functions in the body, including glycogen storage, decomposition of red blood cells, plasma protein synthesis, hormone production, and detoxification. It lies below the diaphragm in the thoracic region of the abdomen. It produces bile, an alkaline compound which aids in digestion, via the emulsification of lipids. The liver's highly specialized tissues regulate a wide variety of high-volume biochemical reactions, including the synthesis and breakdown of small and complex molecules, many of which are necessary for normal vital functions.
Medical terms related to the liver often start in hepato- or hepatic from the Greek word for liver, hēpar (ἡπαρ )
Anatom
The liver is a reddish brown organ with four lobes of unequal size and shape. A human liver normally weighs between 1.4–1.6 kg (3.1–3.5 lb),and is a soft, pinkish-brown, triangular organ. It is both the largest internal organ (the skin being the largest organ overall) and the largest gland in the human body.
It is located in the right upper quadrant of the abdominal cavity, resting just below the diaphragm. The liver lies to the right of the stomach and overlies the gallbladder. It is connected to two large blood vessels, one called the hepatic artery and one called the portal vein. The hepatic artery carries blood from the aorta whereas the portal vein carries blood containing digested nutrients from the small intestine and the descending colon. These blood vessels subdivide into capillaries which then lead to a lobule. Each lobule is made up of millions of hepatic cells which are the basic metabolic cells.
Blood flow
The liver receives a dual blood supply from the hepatic portal vein and hepatic arteries. Supplying approximately 75% of the liver's blood supply, the hepatic portal vein carries venous blood drained from the spleen, gastrointestinal tract, and its associated organs. The hepatic arteries supply arterial blood to the liver, accounting for the remainder of its blood flow. Oxygen is provided from both sources; approximately half of the liver's oxygen demand is met by the hepatic portal vein, and half is met by the hepatic arteries.
Blood flows through the sinusoids and empties into the central vein of each lobule. The central veins coalesce into hepatic veins, which leave the liver and empty into the inferior vena cava.
Billiard flow
The term billiard tree is derived from the arboreal branches of the bile ducts. The bile produced in the liver is collected in bile canaliculi, which merge to form bile ducts. Within the liver, these ducts are called intrahepatic (within the liver) bile ducts, and once they exit the liver they are considered extra hepatic (outside the liver). The intrahepatic ducts eventually drain into the right and left hepatic ducts, which merge to form the common hepatic duct. The cystic duct from the gallbladder joins with the common hepatic duct to form the common bile duct.
Bile can either drain directly into the duodenum via the common bile duct or be temporarily stored in the gallbladder via the cystic duct. The common bile duct and the pancreatic duct enter the second part of the duodenum together at the ampullae’s of Vaster
Apart from a patch where it connects to the diaphragm (the so-called "bare area"), the liver is covered entirely by visceral peritoneum, a thin, double-layered membrane that reduces friction against other organs. The peritoneum folds back on itself to form the aciform ligament and the right and left triangular ligaments.
These "lets" are in no way related to the true anatomic ligaments in joints, and have essentially no functional importance, but they are easily recognizable surface landmarks. An exception to this is the aciform ligament, which attaches the liver to the posterior portion of the anterior body wall.
Lobes
Traditional gross anatomy divided the liver into four lobes based on surface features. The aciform ligament is visible on the front (anterior side) of the liver. This divides the liver into a left anatomical lobe, and a right anatomical lobe.
If the liver is flipped over, to look at it from behind (the visceral surface), there are two additional lobes between the right and left. These are the caudate lobe (the more superior), and below this the quadrate lobe.
From behind, the lobes are divided up by the ligament venous and ligament tares (anything left of these is the left lobe), the transverse fissure (or portal hepatics) divides the caudate from the quadrate lobe, and the right societal fossil, which the inferior vena cava runs over, separates these two lobes from the right lobe.
Each of the lobes is made up of lobules; a vein goes from the centre of each lobule which then joins to the hepatic vein to carry blood out from the liver.
On the surface of the lobules there are ducts, veins and arteries that carry fluids to and from them.
Functional anatomy
* or lobe in the case of the caudate lobe.
Each number in the list corresponds to one in the table.
The central area where the common bile duct, hepatic portal vein, and hepatic artery proper enter is the haulm or "portal hepatics". The duct, vein, and artery divide into left and right branches, and the portions of the liver supplied by these branches constitute the functional left and right lobes.
The functional lobes are separated by an imaginary plane joining the gallbladder fosses to the inferior vena cava. The plane separates the liver into the true right and left lobes. The middle hepatic vein also demarcates the true right and left lobes. The right lobe is further divided into an anterior and posterior segment by the right hepatic vein. The left lobe is divided into the medial and lateral segments by the left hepatic vein. The fissure for the ligament terse also separates the medial and lateral segments. The medial segment is also called the quadrate lobe. In the widely used Coquina (or "French") system, the functional lobes are further divided into a total of eight sub segments based on a transverse plane through the bifurcation of the main portal vein. The caudate lobe is a separate structure which receives blood flow from both the right- and left-sided vascular branches.
In other animals
The liver is found in all vertebrates, and is typically the largest visceral organ. Its form varies considerably in different species, and is largely determined by the shape and arrangement of the surrounding organs. Nonetheless, in most species it is divided into right and left lobes; exceptions to this general rule include snakes, where the shape of the body necessitates a simple cigar-like form. The internal structure of the liver is broadly similar in all vertebrates.
An organ sometimes referred to as a liver is found associated with the digestive tract of the primitive chordate Amphioxus. However, this is an enzyme secreting gland, not a metabolic organ, and it is unclear how truly homologous it is to the vertebrate liver.
Physiology
The various functions of the liver are carried out by the liver cells or hepatocytes. Currently, there is no artificial organ or device capable of emulating all the functions of the liver. Some functions can be emulated by liver dialysis, an experimental treatment for liver failure.
Synthesis
Further information: Proteins produced and secreted by the liver
* A large part of amino acid synthesis
* The liver performs several roles in carbohydrate metabolism:
o Gluconeogenesis (the synthesis of glucose from certain amino acids, lactate or glycerol). Note that humans and some other mammals cannot synthesize glucose from glycerol.
o Glycogenolysis (the breakdown of glycogen into glucose)
o Glycogen sis (the formation of glycogen from glucose)(muscle tissues can also do this)
* The liver is responsible for the mainstay of protein metabolism, synthesis as well as degradation
* The liver also performs several roles in lipid metabolism: Cholesterol synthesis
Lip genesis, the production of triglycerides (fats).
* The liver produces coagulation factors I (fibrinogen), II (prothrombin), V, VII, IX, X and XI, as well as protein C, protein S and ant thrombin.
* In the first trimester fetus, the liver is the main site of red blood cell production. By the 32nd week of gestation, the bone marrow has almost completely taken over that task.
* The liver produces and excretes bile (a yellowish liquid) required for emulsifying fats. Some of the bile drains directly into the duodenum, and some is stored in the gallbladder.
* The liver also produces insulin-like growth factor 1 (IGF-1), a polypeptide protein hormone that plays an important role in childhood growth and continues to have anabolic effects in adults.
* The liver is a major site of thrombopoietin production. Thrombopoietin is a glycoprotein hormone that regulates the production of platelets by the bone marrow.
* The breakdown of insulin and other hormones
* The liver breaks down hemoglobin, creating metabolites that are added to bile as pigment (bilirubin and biliverdin).
* The liver breaks down or modifies toxic substances (e.g., methylamine) and most medicinal products in a process called drug metabolism. This sometimes results in oxidations, when the metabolite is more toxic than its precursor. Preferably, the toxins are conjugated to avail excretion in bile or urine.
Eye
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Eye
Eyes are organs that detect light, and convert it to electro-chemical impulses in neurons. The simplest photoreceptors connect light to movement . In higher organisms complex neural pathways exist that connect the eye, via the optic nerve to the visual cortex and other areas of the brain. Complex optical systems with resolving power have come in ten fundamentally different forms, and 96% of animal species possess a complex optical system. Image-resolving eyes are present in molluscs, chordates and arthropods.
The simplest "eyes", such as those in microorganisms, do nothing but detect whether the surroundings are light or dark, which is sufficient for the entrainment of circadian rhythms. From more complex eyes, retinal photosensitive ganglion cells send signals along the retinohypothalamic tract to the suprachiasmatic nuclei to effect circadian adjustment.Contents .
1 Overview
2 Evolution
3 Types of eye
3.1 Normal eyes
3.2 Pit eyes
3.2.1 Spherical lensed eye
3.2.2 Multiple lenses
3.2.3 Refractive cornea
3.2.4 Reflector eyes
3.3 Compound eyes
3.3.1 Apposition eyes
3.3.2 Superposition eyes
3.3.3 Parabolic superposition
3.3.4 Other
3.3.5 Nutrients of the eye
4 Relationship to life requirements
5 Visual acuity
6 Perception of colour
7 Rods and cones
8 Pigmentation
9 See also
10 References
10.1 Notes
10.2 Bibliography
11 External links
Overview
Eye of the wisent,
the European bison
Complex eyes can distinguish shapes and colors. The visual fields of many organisms, especially predators, involve large areas of binocular vision to improve depth perception; in other organisms, eyes are located so as to maximise the field of view, such as in rabbits and horses, which have monocular vision.
The first proto-eyes evolved among animals 600 million years ago, about the time of the Cambrian explosion. The last common ancestor of animals possessed the biochemical toolkit necessary for vision, and more advanced eyes have evolved in 96% of animal species in six of the thirty-plus main phyla. In most vertebrates and some molluscs, the eye works by allowing light to enter it and project onto a light-sensitive panel of cells, known as the retina, at the rear of the eye. The cone cells (for color) and the rod cells (for low-light contrasts) in the retina detect and convert light into neural signals for vision. The visual signals are then transmitted to the brain via the optic nerve. Such eyes are typically roughly spherical, filled with a transparent gel-like substance called the vitreous humour, with a focusing lens and often an iris; the relaxing or tightening of the muscles around the iris change the size of the pupil, thereby regulating the amount of light that enters the eye,[6] and reducing aberrations when there is enough light.
The eyes of cephalopods, fish, amphibians and snakes usually have fixed lens shapes, and focusing vision is achieved by telescoping the lens — similar to how a camera focuses.
Compound eyes are found among the arthropods and are composed of many simple facets which, depending on the details of anatomy, may give either a single pixelated image or multiple images, per eye. Each sensor has its own lens and photosensitive cell(s). Some eyes have up to 28,000 such sensors, which are arranged hexagonally, and which can give a full 360-degree field of vision. Compound eyes are very sensitive to motion. Some arthropods, including many Strepsiptera, have compound eyes of only a few facets, each with a retina capable of creating an image, creating vision. With each eye viewing a different thing, a fused image from all the eyes is produced in the brain, providing very different, high-resolution images.
Possessing detailed hyperspectral color vision, the Mantis shrimp has been reported to have the world's most complex color vision system. Trilobites, which are now extinct, had unique compound eyes. They used clear calcite crystals to form the lenses of their eyes. In this, they differ from most other arthropods, which have soft eyes. The number of lenses in such an eye varied, however: some trilobites had only one, and some had thousands of lenses in one eye.
In contrast to compound eyes, simple eyes are those that have a single lens. For example, jumping spiders have a large pair of simple eyes with a narrow field of view, supported by an array of other, smaller eyes for peripheral vision. Some insect larvae, like caterpillars, have a different type of simple eye (stemmata) which gives a rough image. Some of the simplest eyes, called ocelli, can be found in animals like some of the snails, which cannot actually "see" in the normal sense. They do have photosensitive cells, but no lens and no other means of projecting an image onto these cells. They can distinguish between light and dark, but no more. This enables snails to keep out of direct sunlight. In organisms dwelling near deep-sea vents, compound eyes have been secondarily simplified and adapted to spot the infra-red light produced by the hot vents - in this way the bearers can spot hot springs and avoid being boiled alive.
Evolution
Main article: Evolution of the eye
Photoreception is phylogenetically very old, with various theories of phylogenesis. The common origin (monophyly) of all animal eyes is now widely accepted as fact. This is based upon the shared anatomical and genetic features of all eyes; that is, all modern eyes, varied as they are, have their origins in a proto-eye believed to have evolved some 540 million years ago. The majority of the advancements in early eyes are believed to have taken only a few million years to develop, since the first predator to gain true imaging would have touched off an "arms race. Prey animals and competing predators alike would be at a distinct disadvantage without such capabilities and would be less likely to survive and reproduce. Hence multiple eye types and subtypes developed in parallel.
Eyes in various animals show adaption to their requirements. For example, birds of prey have much greater visual acuity than humans, and some can see ultraviolet light. The different forms of eye in, for example, vertebrates and mollusks are often cited as examples of parallel evolution, despite their distant common ancestry.
The very earliest "eyes", called eyespots, were simple patches of photoreceptor protein in unicellular animals. In multicellular beings, multicellular eyespots evolved, physically similar to the receptor patches for taste and smell. These eyespots could only sense ambient brightness: they could distinguish light and dark, but not the direction of the lightsource.
Through gradual change, as the eyespot depressed into a shallow "cup" shape, the ability to slightly discriminate directional brightness was achieved by using the angle at which the light hit certain cells to identify the source. The pit deepened over time, the opening diminished in size, and the number of photoreceptor cells increased, forming an effective pinhole camera that was capable of dimly distinguishing shapes.
The thin overgrowth of transparent cells over the eye's aperture, originally formed to prevent damage to the eyespot, allowed the segregated contents of the eye chamber to specialize into a transparent humour that optimized colour filtering, blocked harmful radiation, improved the eye's refractive index, and allowed functionality outside of water. The transparent protective cells eventually split into two layers, with circulatory fluid in between that allowed wider viewing angles and greater imaging resolution, and the thickness of the transparent layer gradually increased, in most species with the transparent crystallin protein.
The gap between tissue layers naturally formed a bioconvex shape, an optimally ideal structure for a normal refractive index. Independently, a transparent layer and a nontransparent layer split forward from the lens: the cornea and iris. Separation of the forward layer again forms a humour, the aqueous humour. This increases refractive power and again eases circulatory problems. Formation of a nontransparent ring allows more blood vessels, more circulation, and larger eye sizes.
Types of eye
There are ten different eye layouts — indeed every way of capturing an image known to man, with the exceptions of zoom and Fresnel lenses. Eye types can be categorized into "simple eyes", with one concave chamber, and "compound eyes", which comprise a number of individual lenses laid out on a convex surface. Note that "simple" does not imply a reduced level of complexity or acuity. Indeed, any eye type can be adapted for almost any behavior or environment. The only limitations specific to eye types are that of resolution — the physics of compound eyes prevents them from achieving a resolution better than 1°. Also, superposition eyes can achieve greater sensitivity than apposition eyes, so are better suited to dark-dwelling creatures.Eyes also fall into two groups on the basis of their photoreceptor's cellular construction, with the photoreceptor cells either being cilliated (as in the vertebrates) or rhabdomeric. These two groups are not monophyletic; the cnidaria also possess cilliated cells, and some annelids possess both.
Normal eyes
Simple eyes are rather ubiquitous, and lens-bearing eyes have evolved at least seven times in vertebrates, cephalopods, annelids, crustacea and cubozoa. Pit eyes
Pit eyes, also known as stemma, are eye-spots which may be set into a pit to reduce the angles of light that enters and affects the eyespot, to allow the organism to deduce the angle of incoming light. Found in about 85% of phyla, these basic forms were probably the precursors to more advanced types of "simple eye". They are small, comprising up to about 100 cells covering about 100 µm. The directionality can be improved by reducing the size of the aperture, by incorporating a reflective layer behind the receptor cells, or by filling the pit with a refractile material.
Spherical lensed eye
The resolution of pit eyes can be greatly improved by incorporating a material with a higher refractive index to form a lens, which may greatly reduce the blur radius encountered — hence increasing the resolution obtainable. The most basic form, still seen in some gastropods and annelids, consists of a lens of one refractive index. A far sharper image can be obtained using materials with a high refractive index, decreasing to the edges; this decreases the focal length and thus allows a sharp image to form on the retina. This also allows a larger aperture for a given sharpness of image, allowing more light to enter the lens; and a flatter lens, reducing spherical aberration. Such an inhomogeneous lens is necessary in order for the focal length to drop from about 4 times the lens radius, to 2.5 radii.
Heterogeneous eyes have evolved at least eight times: four or more times in gastropods, once in the copepods, once in the annelids and once in the cephalopods. No aquatic organisms possess homogeneous lenses; presumably the evolutionary pressure for a heterogeneous lens is great enough for this stage to be quickly "outgrown".
This eye creates an image that is sharp enough that motion of the eye can cause significant blurring. To minimize the effect of eye motion while the animal moves, most such eyes have stabilizing eye muscles.
The ocelli of insects bear a simple lens, but their focal point always lies behind the retina; consequently they can never form a sharp image. This capitulates the function of the eye. Ocelli (pit-type eyes of arthropods) blur the image across the whole retina, and are consequently excellent at responding to rapid changes in light intensity across the whole visual field; this fast response is further accelerated by the large nerve bundles which rush the information to the brain. Focusing the image would also cause the sun's image to be focused on a few receptors, with the possibility of damage under the intense light; shielding the receptors would block out some light and thus reduce their sensitivity. This fast response has led to suggestions that the ocelli of insects are used mainly in flight, because they can be used to detect sudden changes in which way is up (because light, especially UV light which is absorbed by vegetation, usually comes from above).
Multiple lenses
Some marine organisms bear more than one lens; for instance the copepod Pontella has three. The outer has a parabolic surface, countering the effects of spherical aberration while allowing a sharp image to be formed. Another copepod, Copilia's eyes have two lenses, arranged like those in a telescope. Such arrangements are rare and poorly understood, but represent an interesting alternative construction. An interesting use of multiple lenses is seen in some hunters such as eagles and jumping spiders, which have a refractive cornea (discussed next): these have a negative lens, enlarging the observed image by up to 50% over the receptor cells, thus increasing their optical resolution.
Refractive cornea
In the eyes of most mammals, birds, reptiles, and most other terrestrial vertebrates (along with spiders and some insect larvae) the vitreous fluid has a higher refractive index than the air, relieving the lens of the function of reducing the focal length. This has freed it up for fine adjustments of focus, allowing a very high resolution to be obtained. As with spherical lenses, the problem of spherical aberration caused by the lens can be countered either by using an inhomogeneous lens material, or by flattening the lens. Flattening the lens has a disadvantage: the quality of vision is diminished away from the main line of focus, meaning that animals requiring all-round vision are detrimented. Such animals often display an inhomogeneous lens instead.
As mentioned above, a refractive cornea is only useful out of water; in water, there is no difference in refractive index between the vitreous fluid and the surrounding water. Hence creatures which have returned to the water — penguins and seals, for example — lose their refractive cornea and return to lens-based vision. An alternative solution, borne by some divers, is to have a very strong cornea.
Reflector eyes
An alternative to a lens is to line the inside of the eye with " mirrors", and reflect the image to focus at a central point. The nature of these eyes means that if one were to peer into the pupil of an eye, one would see the same image that the organism would see, reflected back out.
Many small organisms such as rotifers, copeopods and platyhelminths use such organs, but these are too small to produce usable images. Some larger organisms, such as scallops, also use reflector eyes. The scallop Pecten has up to 100 millimeter-scale reflector eyes fringing the edge of its shell. It detects moving objects as they pass successive lenses.
There is at least one vertebrate, the spookfish, whose eyes include reflective optics for focusing of light. Each of the two eyes of a spookfish collects light from both above and below; the light coming from the above is focused by a lens, while that coming from below, by a curved mirror composed of many layers of small reflective plates made of guanine crystals.
Compound eyes
An image of a house fly compound eye surface by using Scanning Electron Microscope at X457 magnification
Arthropods such as this carpenter bee have compound eyes
A compound eye may consist of thousands of individual photoreceptor units. The image perceived is a combination of inputs from the numerous ommatidia (individual "eye units"), which are located on a convex surface, thus pointing in slightly different directions. Compared with simple eyes, compound eyes possess a very large view angle, and can detect fast movement and, in some cases, the polarization of light. Because the individual lenses are so small, the effects of diffraction impose a limit on the possible resolution that can be obtained. This can only be countered by increasing lens size and number. To see with a resolution comparable to our simple eyes, humans would require compound eyes which would each reach the size of their head.
Compound eyes fall into two groups: apposition eyes, which form multiple inverted images, and superposition eyes, which form a single erect image.Compound eyes are common in arthropods, and are also present in annelids and some bivalved molluscs.
Compound eyes, in arthropods at least, grow at their margins by the addition of new ommatidia.
Structure of the ommatidia of appositon compound eyes
Apposition eyes
Apposition eyes are the most common form of eye, and are presumably the ancestral form of compound eye. They are found in all arthropod groups, although they may have evolved more than once within this phylum.[2] Some annelids and bivalves also have apposition eyes. They are also possessed by Limulus, the horseshoe crab, and there are suggestions that other chelicerates developed their simple eyes by reduction from a compound starting point. (Some caterpillars appear to have evolved compound eyes from simple eyes in the opposite fashion.)
Apposition eyes work by gathering a number of images, one from each eye, and combining them in the brain, with each eye typically contributing a single point of information.
The typical apposition eye has a lens focusing light from one direction on the rhabdom, while light from other directions is absorbed by the dark wall of the ommatidium. In the other kind of apposition eye, found in the Strepsiptera, lenses are not fused to one another, and each forms an entire image; these images are combined in the brain. This is called the schizochroal compound eye or the neural superposition eye. Because images are combined additively, this arrangement allows vision under lower light levels.
Superposition eyes
The second type is named the superposition eye. The superposition eye is divided into three types; the refracting, the reflecting and the parabolic superposition eye. The refracting superposition eye has a gap between the lens and the rhabdom, and no side wall. Each lens takes light at an angle to its axis and reflects it to the same angle on the other side. The result is an image at half the radius of the eye, which is where the tips of the rhabdoms are. This kind is used mostly by nocturnal insects. In the parabolic superposition compound eye type, seen in arthropods such as mayflies, the parabolic surfaces of the inside of each facet focus light from a reflector to a sensor array. Long-bodied decapod crustaceans such as shrimp, prawns, crayfish and lobsters are alone in having reflecting superposition eyes, which also has a transparent gap but uses corner mirrors instead of lenses.
Parabolic superposition
This eye type functions by refracting light, then using a parabolic mirror to focus the image; it combines features of superposition and apposition eyes.Other
The compound eye of a dragonfly
Good fliers like flies or honey bees, or prey-catching insects like praying mantis or dragonflies, have specialized zones of ommatidia organized into a fovea area which gives acute vision. In the acute zone the eyes are flattened and the facets larger. The flattening allows more ommatidia to receive light from a spot and therefore higher resolution.
There are some exceptions from the types mentioned above. Some insects have a so-called single lens compound eye, a transitional type which is something between a superposition type of the multi-lens compound eye and the single lens eye found in animals with simple eyes. Then there is the mysid shrimp Dioptromysis paucispinosa. The shrimp has an eye of the refracting superposition type, in the rear behind this in each eye there is a single large facet that is three times in diameter the others in the eye and behind this is an enlarged crystalline cone. This projects an upright image on a specialized retina. The resulting eye is a mixture of a simple eye within a compound eye.
Another version is the pseudofaceted eye, as seen in Scutigera. This type of eye consists of a cluster of numerous ocelli on each side of the head, organized in a way that resembles a true compound eye.
The body of Ophiocoma wendtii, a type of brittle star, is covered with ommatidia, turning its whole skin into a compound eye. The same is true of many chitons.
Nutrients of the eye
The ciliary body is the circumferential tissue inside the eye composed of the ciliary muscle and ciliary processes.[1] It is triangular in horizontal section and is coated by a double layer, the ciliary epithelium. This epithelium produces the aqueous humor. The inner layer is transparent and covers the vitreous body, and is continuous from the neural tissue of the retina. The outer layer is highly pigmented, continuous with the retinal pigment epithelium, and constitutes the cells of the dilator muscle.
The vitreous is the transparent, colourless, gelatinous mass that fills the space between the lens of the eye and the retina lining the back of the eye.[28] It is produced by certain retinal cells. It is of rather similar composition to the cornea, but contains very few cells (mostly phagocytes which remove unwanted cellular debris in the visual field, as well as the hyalocytes of Balazs of the surface of the vitreous, which reprocess the hyaluronic acid), no blood vessels, and 98-99% of its volume is water (as opposed to 75% in the cornea) with salts, sugars, vitrosin (a type of collagen), a network of collagen type II fibers with the mucopolysaccharide hyaluronic acid, and also a wide array of proteins in micro amounts. Amazingly, with so little solid matter, it tautly holds the eye. The lens, on the other hand, is tightly packed with cells. However, the vitreous has a viscosity two to four times that of pure water, giving it a gelatinous consistency. It also has a refractive index of . Relationship to life requirements
Eyes are generally adapted to the environment and life requirements of the organism which bears them. For instance, the distribution of photoreceptors tends to match the area in which the highest acuity is required, with horizon-scanning organisms, such as those that live on the African plains, having a horizontal line of high-density ganglia, while tree-dwelling creatures which require good all-round vision tend to have a symmetrical distribution of ganglia, with acuity decreasing outwards from the centre.
Of course, for most eye types, it is impossible to diverge from a spherical form, so only the density of optical receptors can be altered. In organisms with compound eyes, it is the number of ommatidia rather than ganglia that reflects the region of highest data acquisition. 23-4 Optical superposition eyes are constrained to a spherical shape, but other forms of compound eyes may deform to a shape where more ommatidia are aligned to, say, the horizon, without altering the size or density of individual ommatidia. Eyes of horizon-scanning organisms have stalks so they can be easily aligned to the horizon when this is inclined, for example if the animal is on a slope.[30] An extension of this concept is that the eyes of predators typically have a zone of very acute vision at their centre, to assist in the identification of prey. In deep water organisms, it may not be the centre of the eye that is enlarged. The hyperiid amphipods are deep water animals that feed on organisms above them. Their eyes are almost divided into two, with the upper region thought to be involved in detecting the silhouettes of potential prey — or predators — against the faint light of the sky above. Accordingly, deeper water hyperiids, where the light against which the silhouettes must be compared is dimmer, have larger "upper-eyes", and may lose the lower portion of their eyes altogether. Depth perception can be enhanced by having eyes which are enlarged in one direction; distorting the eye slightly allows the distance to the object to be estimated with a high degree of accuracy.
Acuity is higher among male organisms that mate in mid-air, as they need to be able to spot and assess potential mates against a very large backdrop. On the other hand, the eyes of organisms which operate in low light levels, such as around dawn and dusk or in deep water, tend to be larger to increase the amount of light that can be captured.
It is not only the shape of the eye that may be affected by lifestyle. Eyes can be the most visible parts of organisms, and this can act as a pressure on organisms to have more transparent eyes at the cost of function.
Eyes may be mounted on stalks to provide better all-round vision, by lifting them above an organism's carapace; this also allows them to track predators or prey without moving the head.
Visual acuity
A hawk's eye
Visual acuity, or resolving power, is "the ability to distinguish fine detail" and is the property of cones. It is often measured in cycles per degree (CPD), which measures an angular resolution, or how much an eye can differentiate one object from another in terms of visual angles. Resolution in CPD can be measured by bar charts of different numbers of white/black stripe cycles. For example, if each pattern is 1.75 cm wide and is placed at 1 m distance from the eye, it will subtend an angle of 1 degree, so the number of white/black bar pairs on the pattern will be a measure of the cycles per degree of that pattern. The highest such number that the eye can resolve as stripes, or distinguish from a gray block, is then the measurement of visual acuity of the eye.
For a human eye with excellent acuity, the maximum theoretical resolution is 50 CPD (1.2 arcminute per line pair, or a 0.35 mm line pair, at 1 m). A rat can resolve only about 1 to 2 CPD.[33] A horse has higher acuity through most of the visual field of its eyes than a human has, but does not match the high acuity of the human eye's central fovea region.
Spherical aberration limits the resolution of a 7 mm pupil to about 3 arcminutes per line pair. At a pupil diameter of 3 mm, the spherical aberration is greatly reduced, resulting in an improved resolution of approximately 1.7 arcminutes per line pair.[34] A resolution of 2 arcminutes per line pair, equivalent to a 1 arcminute gap in an optotype, corresponds to 20/20 (normal vision) in humans.
Perception of colour
"Colour vision is the faculty of the organism to distinguish lights of different spectral qualities." All organisms are restricted to a small range of electromagnetic spectrum; this varies from creature to creature, but is mainly between 400 and 700 nm. This is a rather small section of the electromagnetic spectrum, probably reflecting the submarine evolution of the organ: water blocks out all but two small windows of the EM spectrum, and there has been no evolutionary pressure among land animals to broaden this range.
The most sensitive pigment, rhodopsin, has a peak response at 500 nm.Small changes to the genes coding for this protein can tweak the peak response by a few nm; pigments in the lens can also "filter" incoming light, changing the peak response. Many organisms are unable to discriminate between colors, seeing instead in shades of "grey"; colour vision necessitates a range of pigment cells which are primarily sensitive to smaller ranges of the spectrum. In primates, geckos, and other organisms, these take the form of cone cells, from which the more sensitive rod cells evolved. Even if organisms are physically capable of discriminating different colours, this does not necessarily mean that they can perceive the different colours; only with behavioral tests can this be deduced.
Most organisms with colour vision are able to detect ultraviolet light. This high energy light can be damaging to receptor cells. With a few exceptions (snakes, placental mammals), most organisms avoid these effects by having absorbent oil droplets around their cone cells. The alternative, developed by organisms that had lost these oil droplets in the course of evolution, is to make the lens impervious to UV light — this precludes the possibility of any UV light being detected, as it does not even reach the retina.
Rods and cones
The retina contains two major types of light-sensitive photoreceptor cells used for vision: the rods and the cones.
Rods cannot distinguish colors, but are responsible for low-light (scotopic) monochrome (black-and-white) vision; they work well in dim light as they contain a pigment, rhodopsin (visual purple), which is sensitive at low light intensity, but saturates at higher (photopic) intensities. Rods are distributed throughout the retina but there are none at the fovea and none at the blind spot. Rod density is greater in the peripheral retina than in the central retina.
Cones are responsible for color vision. They require brighter light to function than rods require. In humans, there are three types of cones, maximally sensitive to long-wavelength, medium-wavelength, and short-wavelength light (often referred to as red, green, and blue, respectively, though the sensitivity peaks are not actually at these colors). The color seen is the combined effect of stimuli to, and responses from, these three types of cone cells. Cones are mostly concentrated in and near the fovea. Only a few are present at the sides of the retina. Objects are seen most sharply in focus when their images fall on the fovea, as when one looks at an object directly. Cone cells and rods are connected through intermediate cells in the retina to nerve fibers of the optic nerve. When rods and cones are stimulated by light, the nerves send off impulses through these fibers to the brain.
Pigmentation
The pigment molecules used in the eye are various, but can be used to define the evolutionary distance between different groups, and can also be an aid in determining which are closely related – although problems of convergence do exist.
Opsins are the pigments involved in photoreception. Other pigments, such as melanin, are used to shield the photoreceptor cells from light leaking in from the sides. The opsin protein group evolved long before the last common ancestor of animals, and has continued to diversify since.
There are two types of opsin involved in vision; c-opsins, which are associated with ciliary-type photoreceptor cells, and r-opsins, associated with rhabdomeric photoreceptor cells. The eyes of vertebrates usually contain cilliary cells with c-opsins, and (bilaterian) invertebrates have rhabdomeric cells in the eye with r-opsins. However, some ganglion cells of vertebrates express r-opsins, suggesting that their ancestors used this pigment in vision, and that remnants survive in the eyes. Likewise, c-opsins have been found to be expressed in the brain of some invertebrates. They may have been expressed in ciliary cells of larval eyes, which were subsequently resorbed into the brain on metamorphosis to the adult form. C-opsins are also found in some derived bilaterian-invertebrate eyes, such as the pallial eyes of the bivalve molluscs; however, the lateral eyes (which were presumably the ancestral type for this group, if eyes evolved once there) always use r-opsins. Cnidaria, which are an outgroup to the taxa mentioned above, express c-opsins - but r-opsins are yet to be found in this group. Incidentally, the melanin produced in the cnidaria is produced in the same fashion as that in vertebrates, suggesting the common descent of this pigment
Eyes are organs that detect light, and convert it to electro-chemical impulses in neurons. The simplest photoreceptors connect light to movement . In higher organisms complex neural pathways exist that connect the eye, via the optic nerve to the visual cortex and other areas of the brain. Complex optical systems with resolving power have come in ten fundamentally different forms, and 96% of animal species possess a complex optical system. Image-resolving eyes are present in molluscs, chordates and arthropods.
The simplest "eyes", such as those in microorganisms, do nothing but detect whether the surroundings are light or dark, which is sufficient for the entrainment of circadian rhythms. From more complex eyes, retinal photosensitive ganglion cells send signals along the retinohypothalamic tract to the suprachiasmatic nuclei to effect circadian adjustment.Contents .
1 Overview
2 Evolution
3 Types of eye
3.1 Normal eyes
3.2 Pit eyes
3.2.1 Spherical lensed eye
3.2.2 Multiple lenses
3.2.3 Refractive cornea
3.2.4 Reflector eyes
3.3 Compound eyes
3.3.1 Apposition eyes
3.3.2 Superposition eyes
3.3.3 Parabolic superposition
3.3.4 Other
3.3.5 Nutrients of the eye
4 Relationship to life requirements
5 Visual acuity
6 Perception of colour
7 Rods and cones
8 Pigmentation
9 See also
10 References
10.1 Notes
10.2 Bibliography
11 External links
Overview
Eye of the wisent,
the European bison
Complex eyes can distinguish shapes and colors. The visual fields of many organisms, especially predators, involve large areas of binocular vision to improve depth perception; in other organisms, eyes are located so as to maximise the field of view, such as in rabbits and horses, which have monocular vision.
The first proto-eyes evolved among animals 600 million years ago, about the time of the Cambrian explosion. The last common ancestor of animals possessed the biochemical toolkit necessary for vision, and more advanced eyes have evolved in 96% of animal species in six of the thirty-plus main phyla. In most vertebrates and some molluscs, the eye works by allowing light to enter it and project onto a light-sensitive panel of cells, known as the retina, at the rear of the eye. The cone cells (for color) and the rod cells (for low-light contrasts) in the retina detect and convert light into neural signals for vision. The visual signals are then transmitted to the brain via the optic nerve. Such eyes are typically roughly spherical, filled with a transparent gel-like substance called the vitreous humour, with a focusing lens and often an iris; the relaxing or tightening of the muscles around the iris change the size of the pupil, thereby regulating the amount of light that enters the eye,[6] and reducing aberrations when there is enough light.
The eyes of cephalopods, fish, amphibians and snakes usually have fixed lens shapes, and focusing vision is achieved by telescoping the lens — similar to how a camera focuses.
Compound eyes are found among the arthropods and are composed of many simple facets which, depending on the details of anatomy, may give either a single pixelated image or multiple images, per eye. Each sensor has its own lens and photosensitive cell(s). Some eyes have up to 28,000 such sensors, which are arranged hexagonally, and which can give a full 360-degree field of vision. Compound eyes are very sensitive to motion. Some arthropods, including many Strepsiptera, have compound eyes of only a few facets, each with a retina capable of creating an image, creating vision. With each eye viewing a different thing, a fused image from all the eyes is produced in the brain, providing very different, high-resolution images.
Possessing detailed hyperspectral color vision, the Mantis shrimp has been reported to have the world's most complex color vision system. Trilobites, which are now extinct, had unique compound eyes. They used clear calcite crystals to form the lenses of their eyes. In this, they differ from most other arthropods, which have soft eyes. The number of lenses in such an eye varied, however: some trilobites had only one, and some had thousands of lenses in one eye.
In contrast to compound eyes, simple eyes are those that have a single lens. For example, jumping spiders have a large pair of simple eyes with a narrow field of view, supported by an array of other, smaller eyes for peripheral vision. Some insect larvae, like caterpillars, have a different type of simple eye (stemmata) which gives a rough image. Some of the simplest eyes, called ocelli, can be found in animals like some of the snails, which cannot actually "see" in the normal sense. They do have photosensitive cells, but no lens and no other means of projecting an image onto these cells. They can distinguish between light and dark, but no more. This enables snails to keep out of direct sunlight. In organisms dwelling near deep-sea vents, compound eyes have been secondarily simplified and adapted to spot the infra-red light produced by the hot vents - in this way the bearers can spot hot springs and avoid being boiled alive.
Evolution
Main article: Evolution of the eye
Photoreception is phylogenetically very old, with various theories of phylogenesis. The common origin (monophyly) of all animal eyes is now widely accepted as fact. This is based upon the shared anatomical and genetic features of all eyes; that is, all modern eyes, varied as they are, have their origins in a proto-eye believed to have evolved some 540 million years ago. The majority of the advancements in early eyes are believed to have taken only a few million years to develop, since the first predator to gain true imaging would have touched off an "arms race. Prey animals and competing predators alike would be at a distinct disadvantage without such capabilities and would be less likely to survive and reproduce. Hence multiple eye types and subtypes developed in parallel.
Eyes in various animals show adaption to their requirements. For example, birds of prey have much greater visual acuity than humans, and some can see ultraviolet light. The different forms of eye in, for example, vertebrates and mollusks are often cited as examples of parallel evolution, despite their distant common ancestry.
The very earliest "eyes", called eyespots, were simple patches of photoreceptor protein in unicellular animals. In multicellular beings, multicellular eyespots evolved, physically similar to the receptor patches for taste and smell. These eyespots could only sense ambient brightness: they could distinguish light and dark, but not the direction of the lightsource.
Through gradual change, as the eyespot depressed into a shallow "cup" shape, the ability to slightly discriminate directional brightness was achieved by using the angle at which the light hit certain cells to identify the source. The pit deepened over time, the opening diminished in size, and the number of photoreceptor cells increased, forming an effective pinhole camera that was capable of dimly distinguishing shapes.
The thin overgrowth of transparent cells over the eye's aperture, originally formed to prevent damage to the eyespot, allowed the segregated contents of the eye chamber to specialize into a transparent humour that optimized colour filtering, blocked harmful radiation, improved the eye's refractive index, and allowed functionality outside of water. The transparent protective cells eventually split into two layers, with circulatory fluid in between that allowed wider viewing angles and greater imaging resolution, and the thickness of the transparent layer gradually increased, in most species with the transparent crystallin protein.
The gap between tissue layers naturally formed a bioconvex shape, an optimally ideal structure for a normal refractive index. Independently, a transparent layer and a nontransparent layer split forward from the lens: the cornea and iris. Separation of the forward layer again forms a humour, the aqueous humour. This increases refractive power and again eases circulatory problems. Formation of a nontransparent ring allows more blood vessels, more circulation, and larger eye sizes.
Types of eye
There are ten different eye layouts — indeed every way of capturing an image known to man, with the exceptions of zoom and Fresnel lenses. Eye types can be categorized into "simple eyes", with one concave chamber, and "compound eyes", which comprise a number of individual lenses laid out on a convex surface. Note that "simple" does not imply a reduced level of complexity or acuity. Indeed, any eye type can be adapted for almost any behavior or environment. The only limitations specific to eye types are that of resolution — the physics of compound eyes prevents them from achieving a resolution better than 1°. Also, superposition eyes can achieve greater sensitivity than apposition eyes, so are better suited to dark-dwelling creatures.Eyes also fall into two groups on the basis of their photoreceptor's cellular construction, with the photoreceptor cells either being cilliated (as in the vertebrates) or rhabdomeric. These two groups are not monophyletic; the cnidaria also possess cilliated cells, and some annelids possess both.
Normal eyes
Simple eyes are rather ubiquitous, and lens-bearing eyes have evolved at least seven times in vertebrates, cephalopods, annelids, crustacea and cubozoa. Pit eyes
Pit eyes, also known as stemma, are eye-spots which may be set into a pit to reduce the angles of light that enters and affects the eyespot, to allow the organism to deduce the angle of incoming light. Found in about 85% of phyla, these basic forms were probably the precursors to more advanced types of "simple eye". They are small, comprising up to about 100 cells covering about 100 µm. The directionality can be improved by reducing the size of the aperture, by incorporating a reflective layer behind the receptor cells, or by filling the pit with a refractile material.
Spherical lensed eye
The resolution of pit eyes can be greatly improved by incorporating a material with a higher refractive index to form a lens, which may greatly reduce the blur radius encountered — hence increasing the resolution obtainable. The most basic form, still seen in some gastropods and annelids, consists of a lens of one refractive index. A far sharper image can be obtained using materials with a high refractive index, decreasing to the edges; this decreases the focal length and thus allows a sharp image to form on the retina. This also allows a larger aperture for a given sharpness of image, allowing more light to enter the lens; and a flatter lens, reducing spherical aberration. Such an inhomogeneous lens is necessary in order for the focal length to drop from about 4 times the lens radius, to 2.5 radii.
Heterogeneous eyes have evolved at least eight times: four or more times in gastropods, once in the copepods, once in the annelids and once in the cephalopods. No aquatic organisms possess homogeneous lenses; presumably the evolutionary pressure for a heterogeneous lens is great enough for this stage to be quickly "outgrown".
This eye creates an image that is sharp enough that motion of the eye can cause significant blurring. To minimize the effect of eye motion while the animal moves, most such eyes have stabilizing eye muscles.
The ocelli of insects bear a simple lens, but their focal point always lies behind the retina; consequently they can never form a sharp image. This capitulates the function of the eye. Ocelli (pit-type eyes of arthropods) blur the image across the whole retina, and are consequently excellent at responding to rapid changes in light intensity across the whole visual field; this fast response is further accelerated by the large nerve bundles which rush the information to the brain. Focusing the image would also cause the sun's image to be focused on a few receptors, with the possibility of damage under the intense light; shielding the receptors would block out some light and thus reduce their sensitivity. This fast response has led to suggestions that the ocelli of insects are used mainly in flight, because they can be used to detect sudden changes in which way is up (because light, especially UV light which is absorbed by vegetation, usually comes from above).
Multiple lenses
Some marine organisms bear more than one lens; for instance the copepod Pontella has three. The outer has a parabolic surface, countering the effects of spherical aberration while allowing a sharp image to be formed. Another copepod, Copilia's eyes have two lenses, arranged like those in a telescope. Such arrangements are rare and poorly understood, but represent an interesting alternative construction. An interesting use of multiple lenses is seen in some hunters such as eagles and jumping spiders, which have a refractive cornea (discussed next): these have a negative lens, enlarging the observed image by up to 50% over the receptor cells, thus increasing their optical resolution.
Refractive cornea
In the eyes of most mammals, birds, reptiles, and most other terrestrial vertebrates (along with spiders and some insect larvae) the vitreous fluid has a higher refractive index than the air, relieving the lens of the function of reducing the focal length. This has freed it up for fine adjustments of focus, allowing a very high resolution to be obtained. As with spherical lenses, the problem of spherical aberration caused by the lens can be countered either by using an inhomogeneous lens material, or by flattening the lens. Flattening the lens has a disadvantage: the quality of vision is diminished away from the main line of focus, meaning that animals requiring all-round vision are detrimented. Such animals often display an inhomogeneous lens instead.
As mentioned above, a refractive cornea is only useful out of water; in water, there is no difference in refractive index between the vitreous fluid and the surrounding water. Hence creatures which have returned to the water — penguins and seals, for example — lose their refractive cornea and return to lens-based vision. An alternative solution, borne by some divers, is to have a very strong cornea.
Reflector eyes
An alternative to a lens is to line the inside of the eye with " mirrors", and reflect the image to focus at a central point. The nature of these eyes means that if one were to peer into the pupil of an eye, one would see the same image that the organism would see, reflected back out.
Many small organisms such as rotifers, copeopods and platyhelminths use such organs, but these are too small to produce usable images. Some larger organisms, such as scallops, also use reflector eyes. The scallop Pecten has up to 100 millimeter-scale reflector eyes fringing the edge of its shell. It detects moving objects as they pass successive lenses.
There is at least one vertebrate, the spookfish, whose eyes include reflective optics for focusing of light. Each of the two eyes of a spookfish collects light from both above and below; the light coming from the above is focused by a lens, while that coming from below, by a curved mirror composed of many layers of small reflective plates made of guanine crystals.
Compound eyes
An image of a house fly compound eye surface by using Scanning Electron Microscope at X457 magnification
Arthropods such as this carpenter bee have compound eyes
A compound eye may consist of thousands of individual photoreceptor units. The image perceived is a combination of inputs from the numerous ommatidia (individual "eye units"), which are located on a convex surface, thus pointing in slightly different directions. Compared with simple eyes, compound eyes possess a very large view angle, and can detect fast movement and, in some cases, the polarization of light. Because the individual lenses are so small, the effects of diffraction impose a limit on the possible resolution that can be obtained. This can only be countered by increasing lens size and number. To see with a resolution comparable to our simple eyes, humans would require compound eyes which would each reach the size of their head.
Compound eyes fall into two groups: apposition eyes, which form multiple inverted images, and superposition eyes, which form a single erect image.Compound eyes are common in arthropods, and are also present in annelids and some bivalved molluscs.
Compound eyes, in arthropods at least, grow at their margins by the addition of new ommatidia.
Structure of the ommatidia of appositon compound eyes
Apposition eyes
Apposition eyes are the most common form of eye, and are presumably the ancestral form of compound eye. They are found in all arthropod groups, although they may have evolved more than once within this phylum.[2] Some annelids and bivalves also have apposition eyes. They are also possessed by Limulus, the horseshoe crab, and there are suggestions that other chelicerates developed their simple eyes by reduction from a compound starting point. (Some caterpillars appear to have evolved compound eyes from simple eyes in the opposite fashion.)
Apposition eyes work by gathering a number of images, one from each eye, and combining them in the brain, with each eye typically contributing a single point of information.
The typical apposition eye has a lens focusing light from one direction on the rhabdom, while light from other directions is absorbed by the dark wall of the ommatidium. In the other kind of apposition eye, found in the Strepsiptera, lenses are not fused to one another, and each forms an entire image; these images are combined in the brain. This is called the schizochroal compound eye or the neural superposition eye. Because images are combined additively, this arrangement allows vision under lower light levels.
Superposition eyes
The second type is named the superposition eye. The superposition eye is divided into three types; the refracting, the reflecting and the parabolic superposition eye. The refracting superposition eye has a gap between the lens and the rhabdom, and no side wall. Each lens takes light at an angle to its axis and reflects it to the same angle on the other side. The result is an image at half the radius of the eye, which is where the tips of the rhabdoms are. This kind is used mostly by nocturnal insects. In the parabolic superposition compound eye type, seen in arthropods such as mayflies, the parabolic surfaces of the inside of each facet focus light from a reflector to a sensor array. Long-bodied decapod crustaceans such as shrimp, prawns, crayfish and lobsters are alone in having reflecting superposition eyes, which also has a transparent gap but uses corner mirrors instead of lenses.
Parabolic superposition
This eye type functions by refracting light, then using a parabolic mirror to focus the image; it combines features of superposition and apposition eyes.Other
The compound eye of a dragonfly
Good fliers like flies or honey bees, or prey-catching insects like praying mantis or dragonflies, have specialized zones of ommatidia organized into a fovea area which gives acute vision. In the acute zone the eyes are flattened and the facets larger. The flattening allows more ommatidia to receive light from a spot and therefore higher resolution.
There are some exceptions from the types mentioned above. Some insects have a so-called single lens compound eye, a transitional type which is something between a superposition type of the multi-lens compound eye and the single lens eye found in animals with simple eyes. Then there is the mysid shrimp Dioptromysis paucispinosa. The shrimp has an eye of the refracting superposition type, in the rear behind this in each eye there is a single large facet that is three times in diameter the others in the eye and behind this is an enlarged crystalline cone. This projects an upright image on a specialized retina. The resulting eye is a mixture of a simple eye within a compound eye.
Another version is the pseudofaceted eye, as seen in Scutigera. This type of eye consists of a cluster of numerous ocelli on each side of the head, organized in a way that resembles a true compound eye.
The body of Ophiocoma wendtii, a type of brittle star, is covered with ommatidia, turning its whole skin into a compound eye. The same is true of many chitons.
Nutrients of the eye
The ciliary body is the circumferential tissue inside the eye composed of the ciliary muscle and ciliary processes.[1] It is triangular in horizontal section and is coated by a double layer, the ciliary epithelium. This epithelium produces the aqueous humor. The inner layer is transparent and covers the vitreous body, and is continuous from the neural tissue of the retina. The outer layer is highly pigmented, continuous with the retinal pigment epithelium, and constitutes the cells of the dilator muscle.
The vitreous is the transparent, colourless, gelatinous mass that fills the space between the lens of the eye and the retina lining the back of the eye.[28] It is produced by certain retinal cells. It is of rather similar composition to the cornea, but contains very few cells (mostly phagocytes which remove unwanted cellular debris in the visual field, as well as the hyalocytes of Balazs of the surface of the vitreous, which reprocess the hyaluronic acid), no blood vessels, and 98-99% of its volume is water (as opposed to 75% in the cornea) with salts, sugars, vitrosin (a type of collagen), a network of collagen type II fibers with the mucopolysaccharide hyaluronic acid, and also a wide array of proteins in micro amounts. Amazingly, with so little solid matter, it tautly holds the eye. The lens, on the other hand, is tightly packed with cells. However, the vitreous has a viscosity two to four times that of pure water, giving it a gelatinous consistency. It also has a refractive index of . Relationship to life requirements
Eyes are generally adapted to the environment and life requirements of the organism which bears them. For instance, the distribution of photoreceptors tends to match the area in which the highest acuity is required, with horizon-scanning organisms, such as those that live on the African plains, having a horizontal line of high-density ganglia, while tree-dwelling creatures which require good all-round vision tend to have a symmetrical distribution of ganglia, with acuity decreasing outwards from the centre.
Of course, for most eye types, it is impossible to diverge from a spherical form, so only the density of optical receptors can be altered. In organisms with compound eyes, it is the number of ommatidia rather than ganglia that reflects the region of highest data acquisition. 23-4 Optical superposition eyes are constrained to a spherical shape, but other forms of compound eyes may deform to a shape where more ommatidia are aligned to, say, the horizon, without altering the size or density of individual ommatidia. Eyes of horizon-scanning organisms have stalks so they can be easily aligned to the horizon when this is inclined, for example if the animal is on a slope.[30] An extension of this concept is that the eyes of predators typically have a zone of very acute vision at their centre, to assist in the identification of prey. In deep water organisms, it may not be the centre of the eye that is enlarged. The hyperiid amphipods are deep water animals that feed on organisms above them. Their eyes are almost divided into two, with the upper region thought to be involved in detecting the silhouettes of potential prey — or predators — against the faint light of the sky above. Accordingly, deeper water hyperiids, where the light against which the silhouettes must be compared is dimmer, have larger "upper-eyes", and may lose the lower portion of their eyes altogether. Depth perception can be enhanced by having eyes which are enlarged in one direction; distorting the eye slightly allows the distance to the object to be estimated with a high degree of accuracy.
Acuity is higher among male organisms that mate in mid-air, as they need to be able to spot and assess potential mates against a very large backdrop. On the other hand, the eyes of organisms which operate in low light levels, such as around dawn and dusk or in deep water, tend to be larger to increase the amount of light that can be captured.
It is not only the shape of the eye that may be affected by lifestyle. Eyes can be the most visible parts of organisms, and this can act as a pressure on organisms to have more transparent eyes at the cost of function.
Eyes may be mounted on stalks to provide better all-round vision, by lifting them above an organism's carapace; this also allows them to track predators or prey without moving the head.
Visual acuity
A hawk's eye
Visual acuity, or resolving power, is "the ability to distinguish fine detail" and is the property of cones. It is often measured in cycles per degree (CPD), which measures an angular resolution, or how much an eye can differentiate one object from another in terms of visual angles. Resolution in CPD can be measured by bar charts of different numbers of white/black stripe cycles. For example, if each pattern is 1.75 cm wide and is placed at 1 m distance from the eye, it will subtend an angle of 1 degree, so the number of white/black bar pairs on the pattern will be a measure of the cycles per degree of that pattern. The highest such number that the eye can resolve as stripes, or distinguish from a gray block, is then the measurement of visual acuity of the eye.
For a human eye with excellent acuity, the maximum theoretical resolution is 50 CPD (1.2 arcminute per line pair, or a 0.35 mm line pair, at 1 m). A rat can resolve only about 1 to 2 CPD.[33] A horse has higher acuity through most of the visual field of its eyes than a human has, but does not match the high acuity of the human eye's central fovea region.
Spherical aberration limits the resolution of a 7 mm pupil to about 3 arcminutes per line pair. At a pupil diameter of 3 mm, the spherical aberration is greatly reduced, resulting in an improved resolution of approximately 1.7 arcminutes per line pair.[34] A resolution of 2 arcminutes per line pair, equivalent to a 1 arcminute gap in an optotype, corresponds to 20/20 (normal vision) in humans.
Perception of colour
"Colour vision is the faculty of the organism to distinguish lights of different spectral qualities." All organisms are restricted to a small range of electromagnetic spectrum; this varies from creature to creature, but is mainly between 400 and 700 nm. This is a rather small section of the electromagnetic spectrum, probably reflecting the submarine evolution of the organ: water blocks out all but two small windows of the EM spectrum, and there has been no evolutionary pressure among land animals to broaden this range.
The most sensitive pigment, rhodopsin, has a peak response at 500 nm.Small changes to the genes coding for this protein can tweak the peak response by a few nm; pigments in the lens can also "filter" incoming light, changing the peak response. Many organisms are unable to discriminate between colors, seeing instead in shades of "grey"; colour vision necessitates a range of pigment cells which are primarily sensitive to smaller ranges of the spectrum. In primates, geckos, and other organisms, these take the form of cone cells, from which the more sensitive rod cells evolved. Even if organisms are physically capable of discriminating different colours, this does not necessarily mean that they can perceive the different colours; only with behavioral tests can this be deduced.
Most organisms with colour vision are able to detect ultraviolet light. This high energy light can be damaging to receptor cells. With a few exceptions (snakes, placental mammals), most organisms avoid these effects by having absorbent oil droplets around their cone cells. The alternative, developed by organisms that had lost these oil droplets in the course of evolution, is to make the lens impervious to UV light — this precludes the possibility of any UV light being detected, as it does not even reach the retina.
Rods and cones
The retina contains two major types of light-sensitive photoreceptor cells used for vision: the rods and the cones.
Rods cannot distinguish colors, but are responsible for low-light (scotopic) monochrome (black-and-white) vision; they work well in dim light as they contain a pigment, rhodopsin (visual purple), which is sensitive at low light intensity, but saturates at higher (photopic) intensities. Rods are distributed throughout the retina but there are none at the fovea and none at the blind spot. Rod density is greater in the peripheral retina than in the central retina.
Cones are responsible for color vision. They require brighter light to function than rods require. In humans, there are three types of cones, maximally sensitive to long-wavelength, medium-wavelength, and short-wavelength light (often referred to as red, green, and blue, respectively, though the sensitivity peaks are not actually at these colors). The color seen is the combined effect of stimuli to, and responses from, these three types of cone cells. Cones are mostly concentrated in and near the fovea. Only a few are present at the sides of the retina. Objects are seen most sharply in focus when their images fall on the fovea, as when one looks at an object directly. Cone cells and rods are connected through intermediate cells in the retina to nerve fibers of the optic nerve. When rods and cones are stimulated by light, the nerves send off impulses through these fibers to the brain.
Pigmentation
The pigment molecules used in the eye are various, but can be used to define the evolutionary distance between different groups, and can also be an aid in determining which are closely related – although problems of convergence do exist.
Opsins are the pigments involved in photoreception. Other pigments, such as melanin, are used to shield the photoreceptor cells from light leaking in from the sides. The opsin protein group evolved long before the last common ancestor of animals, and has continued to diversify since.
There are two types of opsin involved in vision; c-opsins, which are associated with ciliary-type photoreceptor cells, and r-opsins, associated with rhabdomeric photoreceptor cells. The eyes of vertebrates usually contain cilliary cells with c-opsins, and (bilaterian) invertebrates have rhabdomeric cells in the eye with r-opsins. However, some ganglion cells of vertebrates express r-opsins, suggesting that their ancestors used this pigment in vision, and that remnants survive in the eyes. Likewise, c-opsins have been found to be expressed in the brain of some invertebrates. They may have been expressed in ciliary cells of larval eyes, which were subsequently resorbed into the brain on metamorphosis to the adult form. C-opsins are also found in some derived bilaterian-invertebrate eyes, such as the pallial eyes of the bivalve molluscs; however, the lateral eyes (which were presumably the ancestral type for this group, if eyes evolved once there) always use r-opsins. Cnidaria, which are an outgroup to the taxa mentioned above, express c-opsins - but r-opsins are yet to be found in this group. Incidentally, the melanin produced in the cnidaria is produced in the same fashion as that in vertebrates, suggesting the common descent of this pigment
Breast Cancer
| By Unknown
Breast Cancer
Breast cancer (malignant breast neoplasm) is cancers originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas. There are many different types of breast cancer, with different stages (spread), aggressiveness, and genetic makeup; survival varies greatly depending on those factors. Computerized models are available to predict survival.
With best treatment and dependent on staging, 10-year disease-free survival varies from 98% to 10%. Treatment includes surgery, drugs (hormonal therapy and chemotherapy), and radiation.
Worldwide, breast cancer comprises 10.4% of all cancer incidence among women, making it the second most common type of non-skin cancer (after lung cancer) and the fifth most common cause of cancer death. In 2004, breast cancer caused 519,000 deaths worldwide (7% of cancer deaths; almost 1% of all deaths). Breast cancer is about 100 times more common in women than in men, although males tend to have poorer outcomes due to delays in diagnosis.
Some breast cancers require the hormones estrogen and progesterone to grow, and have receptors for those hormones. After surgery those cancers are treated with drugs that interfere with those hormones, usually tamoxifen, and with drugs that shut off the production of estrogen in the ovaries or elsewhere; this may damage the ovaries and end fertility. After surgery, low-risk, hormone-sensitive breast cancers may be treated with hormone therapy and radiation alone. Breast cancers without hormone receptors, or which have spread to the lymph nodes in the armpits, or which express certain genetic characteristics, are higher-risk, and are treated more aggressively. One standard regimen, popular in the U.S., is cyclophosphamide plus doxorubicin (Adriamycin), known as CA; these drugs damage DNA in the cancer, but also in fast-growing normal cells where they cause serious side effects. Sometimes a taxane drug, such as docetaxel, is added, and the regime is then known as CAT; taxane attacks the microtubules in cancer cells. An equivalent treatment, popular in Europe, is cyclophosphamide, methotrexate, and fluorouracil (CMF).[9] Monoclonal antibodies, such as trastuzumab (Herceptin), are used for cancer cells that have the HER2 mutation. Radiation is usually added to the surgical bed to control cancer cells that were missed by the surgery, which usually extends survival, although radiation exposure to the heart may cause damage and heart failure in the following years.
1 Classification
2 Signs and symptoms
3 Risk factors
4 Pathophysiology
5 Diagnosis
6 Screening
7 Treatment
7.1 Medications
7.2 Radiation
8 Prognosis
8.1 Psychological aspects
9 Epidemiology
9.1 United States
9.2 UK
9.3 Developing countries
10 History
11 Society and culture
11.1 Art
12 Cell lines for research
13 See also
14 References
15 External links
Classification
Main article: Breast cancer classification
Breast cancers can be classified by different schemata. Every aspect influences treatment response and prognosis. Description of a breast cancer would optimally include multiple classification aspects, as well as other findings, such as signs found on physical exam. Classification aspects include stage (TNM), pathology, grade, receptor status, and the presence or absence of genes as determined by DNA testing.
Stage. The TNM classification for breast cancer is based on the size of the tumor (T), whether or not the tumor has spread to the lymph nodes (N) in the armpits, and whether the tumor has metastasized (M) (i.e. spread to a more distant part of the body). Larger size, nodal spread, and metastasis have a larger stage number and a worse prognosis.
The main stages are:
Stage 0 is a pre-malignant disease or marker (sometimes called DCIS: Ductal Carcinoma in Situ) .
Stages 1–3 are defined as 'early' cancer and potentially curable.
Stage 4 is defined as 'advanced' and/or 'metastatic' cancer and incurable.
Histopathology. Breast cancer is usually, but not always, primarily classified by its histological appearance. Most breast cancers are' derived from the epithelium lining the ducts or lobules, and are classified as mammary ductal carcinoma. Carcinoma in situ is proliferation of cancer cells within the epithelial tissue without invasion of the surrounding tissue. In contrast, invasive carcinoma invades the surrounding tissue.
Grade (Bloom-Richardson grade). When cells become differentiated, they take different shapes and forms to function as part of an organ. Cancerous cells lose that differentiation. In cancer grading, tumor cells are generally classified as well differentiated (low grade), moderately differentiated (intermediate grade), and poorly differentiated (high grade). Poorly differentiated cancers have a worse prognosis.
Receptor status. Cells have receptors on their surface and in their cytoplasm and nucleus. Chemical messengers such as hormones bind to receptors, and this causes changes in the cell. Breast cancer cells may or may not have three important receptors: estrogen receptor (ER), progesterone receptor (PR), and HER2/neu. Cells with none of these receptors are called basal-like or triple negative. ER+ cancer cells depend on estrogen for their growth, so they can be treated with drugs to block estrogen effects (e.g. tamoxifen), and generally have a better prognosis.
Generally, HER2+ had a worse prognosis, however HER2+ cancer cells respond to drugs such as the monoclonal antibody, trastuzumab, (in combination with conventional chemotherapy) and this has improved the prognosis significantly.
DNA microarrays have compared normal cells to breast cancer cells and found differences in hundreds of genes, but the significance of most of those differences is unknown.
Signs and symptoms
Breast cancer showing an inverted nipple, lump, skin dimpling
The first noticeable symptom of breast cancer is typically a lump that feels different from the rest of the breast tissue. More than 80% of breast cancer cases are discovered when the woman feels a lump.[14] By the time a breast lump is noticeable, it has probably been growing for years. The earliest breast cancers are detected by a mammogram.Lumps found in lymph nodes located in the armpits can also indicate breast cancer.
Indications of breast cancer other than a lump may include changes in breast size or shape, skin dimpling, nipple inversion, or spontaneous single-nipple discharge. Pain ("mastodynia") is an unreliable tool in determining the presence or absence of breast cancer, but may be indicative of other breast health issues.
When breast cancer cells invade the dermal lymphatics—small lymph vessels in the skin of the breast—its presentation can resemble skin inflammation and thus is known as inflammatory breast cancer (IBC). Symptoms of inflammatory breast cancer include pain, swelling, warmth and redness throughout the breast, as well as an orange-peel texture to the skin referred to as peau d'orange.
Another reported symptom complex of breast cancer is Paget's disease of the breast. This syndrome presents as eczematoid skin changes such as redness and mild flaking of the nipple skin. As Paget's advances, symptoms may include tingling, itching, increased sensitivity, burning, and pain. There may also be discharge from the nipple. Approximately half of women diagnosed with Paget's also have a lump in the breast.
Occasionally, breast cancer presents as metastatic disease, that is, cancer that has spread beyond the original organ. Metastatic breast cancer will cause symptoms that depend on the location of metastasis. Common sites of metastasis include bone, liver, lung and brain. Unexplained weight loss can occasionally herald an occult breast cancer, as can symptoms of fevers or chills. Bone or joint pains can sometimes be manifestations of metastatic breast cancer, as can jaundice or neurological symptoms. These symptoms are "non-specific", meaning they can also be manifestations of many other illnesses.
Most symptoms of breast disorder do not turn out to represent underlying breast cancer. Benign breast diseases such as mastitis and fibroadenoma of the breast are more common causes of breast disorder symptoms. The appearance of a new symptom should be taken seriously by both patients and their doctors, because of the possibility of an underlying breast cancer at almost any age.
Risk factors
Main article: Risk factors of breast cancer
The primary risk factors that have been identified are sex,age,lack of childbearing or breastfeeding,and higher hormone levels,
In a study published in 1995, well-established risk factors accounted for 47% of cases while only 5% were attributable to hereditary syndromes.
Genetic factors usually increase the risk slightly or moderately; the exception is women and men who are carriers of BRCA mutations. These people have a very high lifetime risk for breast and ovarian cancer, depending on the portion of the proteins where the mutation occurs. Instead of a 12 percent lifetime risk of breast cancer, women with one of these genes has a risk of approximately 60 percent. In more recent years, research has indicated the impact of diet and other behaviors on breast cancer. These additional risk factors include a high-fat diet,
alcohol intake, obesity, and environmental factors such as tobacco use, radiation, endocrine disruptors and shiftwork.
Although the radiation from mammography is a low dose, the cumulative effect can cause cancer.
In addition to the risk factors specified above, demographic and medical risk factors include.
Personal history of breast cancer: A woman who had breast cancer in one breast has an increased risk of getting cancer in her other breast.
Family history: A woman's risk of breast cancer is higher if her mother, sister, or daughter had breast cancer. The risk is higher if her family member got breast cancer before age 40. Having other relatives with breast cancer (in either her mother's or father's family) may also increase a woman's risk.
Certain breast changes: Some women have cells in the breast that look abnormal under a microscope. Having certain types of abnormal cells (atypical hyperplasia and lobular carcinoma in situ ) increases the risk of breast cancer.
Race: Breast cancer is diagnosed more often in women of European ancestry than those of African or Asian ancestry.
A National Cancer Institute (NCI) study of 72,000 women found that those who had a normal body mass index at age 20 and gained weight as they aged had nearly double the risk of developing breast cancer after menopause in comparison to women maintained their weight. The average 60 year-old woman's risk of developing breast cancer by age 65 is about 2 percent; her lifetime risk is 13 percent.
Abortion has not been found to be a risk factor for breast cancer. The breast cancer abortion hypothesis, however, continues to be promoted by some pro-life groups.
The United Kingdom is the member of International Cancer Genome Consortium that is leading efforts to map breast cancer's complete genome.
Pathophysiology
Main article: Carcinogenesis
Overview of signal transduction pathways involved in apoptosis. Mutations leading to loss of apoptosis can lead to tumorigenesis.
Breast cancer, like other cancers, occurs because of an interaction between the environment and a defective gene. Normal cells divide as many times as needed and stop. They attach to other cells and stay in place in tissues. Cells become cancerous when mutations destroy their ability to stop dividing, to attach to other cells and to stay where they belong. When cells divide, their DNA is normally copied with many mistakes. Error-correcting proteins fix those mistakes. The mutations known to cause cancer, such as p53, BRCA1 and BRCA2, occur in the error-correcting mechanisms. These mutations are either inherited or acquired after birth. Presumably, they allow the other mutations, which allow uncontrolled division, lack of attachment, and metastasis to distant organs.
Normal cells will commit cell suicide (apoptosis) when they are no longer needed. Until then, they are protected from cell suicide by several protein clusters and pathways. One of the protective pathways is the PI3K/AKT pathway; another is the RAS/MEK/ERK pathway. Sometimes the genes along these protective pathways are mutated in a way that turns them permanently "on", rendering the cell incapable of committing suicide when it is no longer needed. This is one of the steps that causes cancer in combination with other mutations. Normally, the PTEN protein turns off the PI3K/AKT pathway when the cell is ready for cell suicide. In some breast cancers, the gene for the PTEN protein is mutated, so the PI3K/AKT pathway is stuck in the "on" position, and the cancer cell does not commit suicide.
Mutations that can lead to breast cancer have been experimentally linked to estrogen exposure.
Failure of immune surveillance, the removal of malignant cells throughout one's life by the immune system.
Abnormal growth factor signaling in the interaction between stromal cells and epithelial cells can facilitate malignant cell growth.
People in less-developed countries report lower incidence rates than in developed countries.
In the United States, 10 to 20 percent of patients with breast cancer and patients with ovarian cancer have a first- or second-degree relative with one of these diseases. Mutations in either of two major susceptibility genes, breast cancer susceptibility gene 1 (BRCA1) and breast cancer susceptibility gene 2 (BRCA2), confer a lifetime risk of breast cancer of between 60 and 85 percent and a lifetime risk of ovarian cancer of between 15 and 40 percent. However, mutations in these genes account for only 2 to 3 percent of all breast cancers.
Diagnosis This section does not cite any references or sources.
Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (October 2007)
While screening techniques (which are further discussed below) are useful in determining the possibility of cancer, a further testing is necessary to confirm whether a lump detected on screening is cancer, as opposed to a benign alternative such as a simple cyst.
In a clinical setting, breast cancer is commonly diagnosed using a "triple test" of clinical breast examination (breast examination by a trained medical practitioner), mammography, and fine needle aspiration cytology. Both mammography and clinical breast exam, also used for screening, can indicate an approximate likelihood that a lump is cancer, and may also identify any other lesions. Fine Needle Aspiration and Cytology (FNAC), which may be done in a GP's office using local anaesthetic if required, involves attempting to extract a small portion of fluid from the lump. Clear fluid makes the lump highly unlikely to be cancerous, but bloody fluid may be sent off for inspection under a microscope for cancerous cells. Together, these three tools can be used to diagnose breast cancer with a good degree of accuracy.
Other options for biopsy include core biopsy, where a section of the breast lump is removed, and an excisional biopsy, where the entire lump is removed.
In addition vacuum-assisted breast biopsy (VAB) may help diagnose breast cancer among patients with a mammographically detected breast in women according to a systematic review .[48] In this study, summary estimates for vacuum assisted breast biopsy in diagnosis of breast cancer were as follows sensitivity was 98.1% with 95% CI = 0.972-0.987 and specificity was 100% with 95% CI = 0.997-0.999. However underestimate rates of atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) were 20.9% with 95% CI =0.177-0.245 and 11.2% with 95% CI = 0.098-0.128 respectively.
Excised human breast tissue, showing an irregular, dense, white stellate area of cancer 2 cm in diameter, within yellow fatty tissue.
Micrograph showing a lymph node invaded by ductal breast carcinoma and with extranodal extension of tumour.
Neuropilin-2 expression in normal breast and breast carcinoma tissue.
Lymph nodes which drain the breast
F-18 FDG PET/CT: Metastasis of a mamma carcinoma in the right scapula
Screening
Main article: Breast cancer screening
Breast cancer screening refers to testing otherwise-healthy women for breast cancer in an attempt to achieve an earlier diagnosis. The assumption is that early detection will improve outcomes. A number of screening test have been employed including: clinical and self breast exams, mammography, genetic screening, ultrasound, and magnetic resonance imaging.
A clinical or self breast exam involves feeling the breast for lumps or other abnormalities. Research evidence does not support the effectiveness of either type of breast exam, because by the time a lump is large enough to be found it is likely to have been growing for several years and will soon be large enough to be found without an exam.
Mammographic screening for breast cancer uses x-rays to examine the breast for any uncharacteristic masses or lumps. The Cochrane collaboration in 2009 concluded that mammograms reduce mortality from breast cancer by 15 percent but also result in unnecessary surgery and anxiety, resulting in their view that mammography screening may do more harm than good.
Many national organizations recommend regular mammography, nevertheless. For the average woman, the U.S. Preventive Services Task Force recommends mammography every two years in women between the ages of 50 and 74.
The Task Force points out that in addition to unnecessary surgery and anxiety, the risks of more frequent mammograms include a small but significant increase in breast cancer induced by radiation.
In women at high risk, such as those with a strong family history of cancer, mammography screening is recommended at an earlier age and additional testing may include genetic screening that tests for the BRCA genes and / or magnetic resonance imaging.
Treatment
Main article: Breast cancer treatment
Breast cancer is sometimes treated first with surgery, and then with chemotherapy, radiation, or both. Treatments are given with increasing aggressiveness according to the prognosis and risk of recurrence.
Stage 1 cancers (and DCIS) have an excellent prognosis and are generally treated with lumpectomy with or without chemotherapy or radiation.
Although the aggressive HER2+ cancers should also be treated with the trastuzumab (Herceptin) regime.
Stage 2 and 3 cancers with a progressively poorer prognosis and greater risk of recurrence are generally treated with surgery (lumpectomy or mastectomy with or without lymph node removal), radiation (sometimes) and chemotherapy (plus trastuzumab for HER2+ cancers).
Stage 4, metastatic cancer, (i.e. spread to distant sites) is not curable and is managed by various combinations of all treatments from surgery, radiation, chemotherapy and targeted therapies. These treatments increase the median survival time of stage 4 breast cancer by about 6 months.
Medications
Drugs used after and in addition to surgery are called adjuvant therapy. Chemotherapy prior to surgery is called neo-adjuvant therapy. There are currently 3 main groups of medications used for adjuvant breast cancer treatment . Hormone Blocking Therapy, Chemotherapy Monoclonal Antibodies One or all of these groups can be used.
Hormone Blocking Therapy: Some breast cancers require estrogen to continue growing. They can be identified by the presence of estrogen receptors (ER+) and progesterone receptors (PR+) on their surface (sometimes referred to together as hormone receptors, HR+). These ER+ cancers can be treated with drugs that either block the receptors, such as tamoxifen, or alternatively block the production of estrogen, such as the aromatase inhibitor, anastrozole (Arimidex).
Chemotherapy: Usually used for stage 1-4 disease. They are given in combinations. One of the most common treatments is cyclophosphamide plus doxorubicin (Adriamycin), known as AC; these drugs damage DNA in the cancer, but also in fast-growing normal cells where they cause serious side effects. Damage to the heart muscle is the most dangerous complication of doxorubicin. Sometimes a taxane drug, such as docetaxel, is added, and the regime is then known as CAT; taxane attacks the microtubules in cancer cells. Another common treatment, which produces equivalent results, is cyclophosphamide, methotrexate, and fluorouracil (CMF). (Chemotherapy can literally refer to any drug, but it is usually used to refer to traditional non-hormone treatments for cancer.)
Monoclonal antibodies: A relatively recent and very exciting development in HER2+ breast cancer treatment. Cancer cells have a receptor called HER2 on their surface. This receptor is normally stimulated by a growth factor which causes the cell to divide, however in the absence of the growth factor, the cell will normally stop growing. In approx 20% of invasive breast cancers, the HER2 receptor is stuck in the "on" position. The cell divides without stopping, producing an aggressive form of cancer. Trastuzumab (Herceptin), a monoclonal antibody to HER2, has dramatically improved the 5yr disease free survival of 'early' (stages 1–3) HER2+ breast cancers to about 87%.
Trastuzumab, however, is expensive, and approx 2% of patients suffer significant heart damage; it is otherwise well tolerated with far milder side effects than conventional chemotherapy.
Other monoclonal antibodies are also being trialled.
Finally, a recent article has claimed that Aspirin may reduce mortality from breast cancer.
Radiation
Radiotherapy is given after surgery to the region of the tumor bed, to destroy microscopic tumors that may have escaped surgery. It may also have a beneficial effect on tumour microenvironment.
Radiation therapy can be delivered as external beam radiotherapy or as brachytherapy (internal radiotherapy). Conventionally radiotherapy is given after the operation for breast cancer. Radiation can also be given, arguably more efficiently, at the time of operation on the breast cancer- intraoperatively. The largest randomised trial to test this approach was the TARGIT-A Trial which found that targeted intraoperative radiotherapy was equally effective at 4-years as the usual several weeks' of whole breast external beam radiotherapy .
Radiation can reduce the risk of recurrence by 50-66% (1/2 - 2/3rds reduction of risk) when delivered in the correct dose
and is considered essential when breast cancer is treated by removing only the lump (Lumpectomy or Wide local excision)
Prognosis
A prognosis is a prediction of outcome, usually the probability of death (or survival), and the probability of progression-free survival (PFS) or disease-free survival (DFS). These predictions are based on experience with breast cancer patients with similar classification. A prognosis is an estimate, as patients with the same classification will survive a different amount of time, and classifications are not always precise. Survival is usually calculated as an average number of months (or years) that 50% of patients survive, or the percentage of patients that are alive after 1, 5, 15 and 20 years. Prognosis is important for treatment decisions because patients with a good prognosis are usually offered less invasive treatments, such as lumpectomy and radiation or hormone therapy, while patients with poor prognosis are usually offered more aggressive treatment, such as more extensive mastectomy and one or more chemotherapy drugs.
Prognostic factors include staging, (i.e., tumor size, location, grade, whether disease has traveled to other parts of the body), recurrence of the disease, and age of patient.Stage is the most important, as it takes into consideration size, local involvement, lymph node status and whether metastatic disease is present. The higher the stage at diagnosis, the worse the prognosis. The stage is raised by the invasiveness of disease to lymph nodes, chest wall, skin or beyond, and the aggressiveness of the cancer cells. The stage is lowered by the presence of cancer-free zones and close-to-normal cell behaviour (grading). Size is not a factor in staging unless the cancer is invasive. For example, Ductal Carcinoma In Situ (DCIS) involving the entire breast will still be stage zero and consequently an excellent prognosis with a 10yr disease free survival of about 98%.
Grading is based on how biopsied, cultured cells behave. The closer to normal cancer cells are, the slower their growth and the better the prognosis. If cells are not well differentiated, they will appear immature, will divide more rapidly, and will tend to spread. Well differentiated is given a grade of 1, moderate is grade 2, while poor or undifferentiated is given a higher grade of 3 or 4 (depending upon the scale used).
Younger women tend to have a poorer prognosis than post-menopausal women due to several factors. Their breasts are active with their cycles, they may be nursing infants, and may be unaware of changes in their breasts. Therefore, younger women are usually at a more advanced stage when diagnosed. There may also be biologic factors contributing to a higher risk of disease recurrence for younger women with breast cancer.
The presence of estrogen and progesterone receptors in the cancer cell is important in guiding treatment. Those who do not test positive for these specific receptors will not be able to respond to hormone therapy, and this can affect their chance of survival depending upon what treatment options remain, the exact type of the cancer, and how advanced the disease is.
In addition to hormone receptors, there are other cell surface proteins that may affect prognosis and treatment. HER2 status directs the course of treatment. Patients whose cancer cells are positive for HER2 have more aggressive disease and may be treated with the 'targeted therapy', trastuzumab (Herceptin), a monoclonal antibody that targets this protein and improves the prognosis significantly. Tumors overexpressing the Wnt signaling pathway co-receptor low-density lipoprotein receptor-related protein 6 (LRP6) may represent a distinct subtype of breast cancer and a potential treatment target.
Psychological aspects
The emotional impact of cancer diagnosis, symptoms, treatment, and related issues can be severe. Most larger hospitals are associated with cancer support groups which provide a supportive environment to help patients cope and gain perspective from cancer survivors. Online cancer support groups are also very beneficial to cancer patients, especially in dealing with uncertainty and body-image problems inherent in cancer treatment.
Not all breast cancer patients experience their illness in the same manner. Factors such as age can have a significant impact on the way a patient copes with a breast cancer diagnosis. Premenopausal women with estrogen-receptor positive breast cancer must confront the issues of early menopause induced by many of the chemotherapy regimens used to treat their breast cancer, especially those that use hormones to counteract ovarian function.
On the other hand, a recent study conducted by researchers at the College of Public Health of the University of Georgia showed that older women may face a more difficult recovery from breast cancer than their younger counterparts.
As the incidence of breast cancer in women over 50 rises and survival rates increase, breast cancer is increasingly becoming a geriatric issue that warrants both further research and the expansion of specialized cancer support services tailored for specific age groups.
Epidemiology
Age-standardized death from breast cancer per 100,000 inhabitants in 2004. no data
less than 2
2-4
4-6
6-8
8-10
10-12
12-14
14-16
16-18
18-20
20-22
more than 22
Worldwide, breast cancer is the most common cancer in women, after skin cancer, representing 16% of all female cancers. The rate is more than twice that of colorectal cancer and cervical cancer and about three times that of lung cancer.Mortality worldwide is 25% greater than that of lung cancer in women. In 2004, breast cancer caused 519,000 deaths worldwide (7% of cancer deaths; almost 1% of all deaths). The number of cases worldwide has significantly increased since the 1970s, a phenomenon partly attributed to the modern lifestyles.
The incidence of breast cancer varies greatly around the world: it is lowest in less-developed countries and greatest in the more-developed countries. In the twelve world regions, the annual age-standardized incidence rates per 100,000 women are as follows: in Eastern Asia, 18; South Central Asia, 22; sub-Saharan Africa, 22; South-Eastern Asia, 26; North Africa and Western Asia, 28; South and Central America, 42; Eastern Europe, 49; Southern Europe, 56; Northern Europe, 73; Oceania, 74; Western Europe, 78; and in North America, 90.
Breast cancer is strongly related to age with only 5% of all breast cancers occur in women under 40 years old. However, it can occur in younger women.
United States
The lifetime risk for breast cancer in the United States is usually given as 1 in 8 (12.5%) with a 1 in 35 (3%) chance of death. A recent analysis however has called this estimate into question when it found a risk of only 6% in healthy women.
The United States has the highest annual incidence rates of breast cancer in the world; 128.6 per 100,000 in whites and 112.6 per 100,000 among African Americans. It is the second-most common cancer (after skin cancer) and the second-most common cause of cancer death (after lung cancer). In 2007, breast cancer was expected to cause 40,910 deaths in the US (7% of cancer deaths; almost 2% of all deaths). This figure includes 450-500 annual deaths among men out of 2000 cancer cases.
In the US, both incidence and death rates for breast cancer have been declining in the last few years in Native Americans and Alaskan Natives. Nevertheless, a US study conducted in 2005 indicated that breast cancer remains the most feared disease,even though heart disease is a much more common cause of death among women. Many doctors say that women exaggerate their risk of breast cancer.
Cancer occurence in females in the United States. Breast cancer is seen in light green at left. By mortality
Racial disparities
Several studies have found that black women in the U.S. are more likely to die from breast cancer even though white women are more likely to be diagnosed with the disease. Even after diagnosis, black women are less likely to get treatment compared to white women. Scholars have advanced several theories for the disparities, including inadequate access to screening, reduced availability of the most advanced surgical and medical techniques, or some biological characteristic of the disease in the African American population. Some studies suggest that the racial disparity in breast cancer outcomes may reflect cultural biases more than biological disease differences. However, the lack of diversity in clinical trials for breast cancer treatment may contribute to these disparities, with recent research indicating that black women are more likely to have estrogen receptor negative breast cancers, which are not responsive to hormone treatments that are effective for most white women.Research is currently ongoing to define the contribution of both biological and cultural factors.
UK
45,000 cases diagnosed and 12,500 deaths per annum. 60% of cases are treated with Tamoxifen, of these the drug becomes ineffective in 35%.
Developing countries
As developing countries grow and adopt Western culture they also accumulate more disease that has arisen from Western culture and its habits (fat/alcohol intake, smoking, exposure to oral contraceptives, the changing patterns of childbearing and breastfeeding, low parity). For instance, as South America has developed so has the amount of breast cancer. Breast cancer in less developed countries, such as those in South America, is a major public health issue. It is a leading cause of cancer-related deaths in women in countries such as Argentina, Uruguay, and Brazil. The expected numbers of new cases and deaths due to breast cancer in South America for the year 2001 are approximately 70,000 and 30,000, respectively. However, because of a lack of funding and resources, treatment is not always available to those suffering with breast cancer.
History
Breast cancer surgery in the 18th century
Breast cancer may be one of the oldest known forms of cancerous tumors in humans. The oldest description of cancer was discovered in Egypt and dates back to approximately 1600 BC. The Edwin Smith Papyrus describes 8 cases of tumors or ulcers of the breast that were treated by cauterization. The writing says about the disease, "There is no treatment. For centuries, physicians described similar cases in their practises, with the same conclusion. It was not until doctors achieved greater understanding of the circulatory system in the 17th century that they could establish a link between breast cancer and the lymph nodes in the armpit. The French surgeon Jean Louis Petit (1674–1750) and later the Scottish surgeon Benjamin Bell (1749–1806) were the first to remove the lymph nodes, breast tissue, and underlying chest muscle. Their successful work was carried on by William Stewart Halsted who started performing mastectomies in 1882. The Halsted radical mastectomy often involved removing both breasts, associated lymph nodes, and the underlying chest muscles. This often led to long-term pain and disability, but was seen as necessary in order to prevent the cancer from recurring.Radical mastectomies remained the standard until the 1970s, when a new understanding of metastasis led to perceiving cancer as a systemic illness as well as a localized one, and more sparing procedures were developed that proved equally effective.
The French surgeon Bernard Peyrilhe (1737–1804) realized the first experimental transmission of cancer by injecting extracts of breast cancer into an animal.
Prominent women who died of breast cancer include Empress Theodora, wife of Justinian; Anne of Austria, mother of Louis XIV of France; Mary Washington, mother of George, and Rachel Carson, the environmentalist.
The first case-controlled study on breast cancer epidemiology was done by Janet Lane-Claypon, who published a comparative study in 1926 of 500 breast cancer cases and 500 control patients of the same background and lifestyle for the British Ministry of Health.
Society and culture
A pink ribbon, the universal symbol of breast cancer awareness.
The widespread acceptance of second opinions before surgery, less invasive surgical procedures, support groups, and other advances in patient care have stemmed, in part, from the breast cancer advocacy movement.
October is recognized as National Breast Cancer Awareness Month by the media as well as survivors, family and friends of survivors and/or victims of the disease. A pink ribbon is worn to recognize the struggle that sufferers face when battling with the cancer. On the meaning of this, see Semiotics of breast cancer pink ribbon.
The patron saint of breast cancer is Agatha of Sicily.
In the fall of 1991, Susan G. Komen for the Cure handed out pink ribbons to participants in its New York City race for breast cancer survivors.
The pink and blue ribbon was designed in 1996 by Nancy Nick, President and Founder of the John W. Nick Foundation to bring awareness that "Men Get Breast Cancer Too!
In 2009 the male breast cancer advocacy groups Out of the Shadow of Pink, A Man's Pink and the Brandon Greening Foundation for Breast Cancer in Men joined together to globally establish the third week of October as "Male Breast Cancer Awareness Week"
In the first quarter of 2009, Anthony L. May the President and Founder of Men For A Cause, United Against Breast Cancer created the very symbolic Official Breast Cancer Awareness Flag to advocate year around breast cancer awareness.
Art
Possible breast cancer signs in historical paintings have been repeatedly discussed in medical literature. A typical lump, differences in breast size or shape and the peau d'orange can be found for example in works by Raphael, Rembrandt and Rubens. However if the visible changes are really dealing with breast cancer can not be proved and was therefore doubted.Examples of breast cancer signs in art
Raffaelo Sanzio (1483-1520): „Portrait of a young woman“ („La Fornarina“)
Peter Paul Rubens (1577–1640): „The Three Graces“
Rembrandt van Rijn (1606–1669): „Bathseba with David's Letter“
Details
Cell lines for research A considerable part of the current knowledge on breast carcinomas is based on in vivo and in vitro studies performed with breast cancer cell (BCC) lines. These provide an unlimited source of homogenous self-replicating material, free of contaminating stromal cells, and often easily cultured in simple standard media. The first line described, BT-20, was established in 1958. Since then, and despite sustained work in this area, the number of permanent lines obtained has been strikingly low (about 100). Indeed, attempts to culture BCC from primary tumors have been largely unsuccessful. This poor efficiency was often due to technical difficulties associated with the extraction of viable tumor cells from their surrounding stroma. Most of the available BCC lines issued from metastatic tumors, mainly from pleural effusions. Effusions provided generally large numbers of dissociated, viable tumor cells with little or no contamination by fibroblasts and other tumor stroma cells. Many of the currently used BCC lines were established in the late 1970s. A very few of them, namely MCF-7, T-47D, and MDA-MB-231, account for more than two-thirds of all abstracts reporting studies on mentioned BCC lines, as concluded from a Medline-based survey.
Treatments are constantly evaluated in randomized, controlled trials, to evaluate and compare individual drugs, combinations of drugs, and surgical and radiation techniques. The latest research is reported annually at scientific meetings such as that of the American Society of Clinical Oncology, San Antonio Breast Cancer Symposium, and the St. Gallen Oncology Conference in St. Gallen, Switzerland. These studies are reviewed by professional societies and other organizations, and formulated into guidelines for specific treatment groups and risk category.
List of cell lines
Mainly based on Lacroix and Leclercq (2004). For more data on the nature of TP53 mutations in breast cancer cell lines, see Lacroix et al. (2006).
This is an incomplete list, which may never be able to satisfy particular standards for completeness. You can help by expanding it with reliably sourced entries.Cell line Primary tumor Origin of cells Estrogen receptors Progesterone receptors ERBB2 amplification Mutated TP53 Tumorigenic in mice Reference
600MPE Invasive ductal carcinoma + - AU565 Adenocarcinoma - - + -
BT-20 Invasive ductal carcinoma Primary No No No Yes Yes
BT-474 Invasive ductal carcinoma Primary Yes Yes Yes Yes Yes
BT-483 Invasive ductal carcinoma + + -
BT-549 Invasive ductal carcinoma - - +
Evsa-T Invasive ductal carcinoma, mucin-producing, signet-ring type Metastasis (ascites) No Yes ? Yes ?
Hs578T Carcinosarcoma Primary No No No Yes No
MCF-7 Invasive ductal carcinoma Metastasis (pleural effusion) Yes
Yes No (wild-type) Yes (with estrogen supplementation)
MDA-MB-231 Invasive ductal carcinoma Metastasis (pleural effusion) No No No Yes Yes
SK-BR-3 Invasive ductal carcinoma Metastasis (pleural effusion) No No Yes Yes No
T-47D Invasive ductal carcinoma Metastasis (pleural effusion) Yes Yes No Yes Yes (with estrogen supplementation)
See also
Male breast cancer
Semiotics of breast cancer pink ribbon
List of notable breast cancer patients according to occupation
List of notable breast cancer patients according to survival status
List of breast carcinogenic substances
Mammary tumor for breast cancer in other animals
Breast reconstruction
External beam radiotherapy
Brachytherapy
Alcohol and cancer
Mammography Quality Standards Act
National Breast Cancer Coalition
National Comprehensive Cancer Network
Breast Cancer Action
Breakthrough Breast Cancer
Living Beyond Breast Cancer
International Agency for Research on Cancer
Susan G. Komen for the Cure
Breast Cancer Network of Strength
Your Disease Risk
Sentinel lymph node Biopsy, a new technique for staging the axilla
Kara Magsanoc-Alikpala Philippine activist against breast cancer.
Breast cancer (malignant breast neoplasm) is cancers originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas. There are many different types of breast cancer, with different stages (spread), aggressiveness, and genetic makeup; survival varies greatly depending on those factors. Computerized models are available to predict survival.
With best treatment and dependent on staging, 10-year disease-free survival varies from 98% to 10%. Treatment includes surgery, drugs (hormonal therapy and chemotherapy), and radiation.
Worldwide, breast cancer comprises 10.4% of all cancer incidence among women, making it the second most common type of non-skin cancer (after lung cancer) and the fifth most common cause of cancer death. In 2004, breast cancer caused 519,000 deaths worldwide (7% of cancer deaths; almost 1% of all deaths). Breast cancer is about 100 times more common in women than in men, although males tend to have poorer outcomes due to delays in diagnosis.
Some breast cancers require the hormones estrogen and progesterone to grow, and have receptors for those hormones. After surgery those cancers are treated with drugs that interfere with those hormones, usually tamoxifen, and with drugs that shut off the production of estrogen in the ovaries or elsewhere; this may damage the ovaries and end fertility. After surgery, low-risk, hormone-sensitive breast cancers may be treated with hormone therapy and radiation alone. Breast cancers without hormone receptors, or which have spread to the lymph nodes in the armpits, or which express certain genetic characteristics, are higher-risk, and are treated more aggressively. One standard regimen, popular in the U.S., is cyclophosphamide plus doxorubicin (Adriamycin), known as CA; these drugs damage DNA in the cancer, but also in fast-growing normal cells where they cause serious side effects. Sometimes a taxane drug, such as docetaxel, is added, and the regime is then known as CAT; taxane attacks the microtubules in cancer cells. An equivalent treatment, popular in Europe, is cyclophosphamide, methotrexate, and fluorouracil (CMF).[9] Monoclonal antibodies, such as trastuzumab (Herceptin), are used for cancer cells that have the HER2 mutation. Radiation is usually added to the surgical bed to control cancer cells that were missed by the surgery, which usually extends survival, although radiation exposure to the heart may cause damage and heart failure in the following years.
1 Classification
2 Signs and symptoms
3 Risk factors
4 Pathophysiology
5 Diagnosis
6 Screening
7 Treatment
7.1 Medications
7.2 Radiation
8 Prognosis
8.1 Psychological aspects
9 Epidemiology
9.1 United States
9.2 UK
9.3 Developing countries
10 History
11 Society and culture
11.1 Art
12 Cell lines for research
13 See also
14 References
15 External links
Classification
Main article: Breast cancer classification
Breast cancers can be classified by different schemata. Every aspect influences treatment response and prognosis. Description of a breast cancer would optimally include multiple classification aspects, as well as other findings, such as signs found on physical exam. Classification aspects include stage (TNM), pathology, grade, receptor status, and the presence or absence of genes as determined by DNA testing.
Stage. The TNM classification for breast cancer is based on the size of the tumor (T), whether or not the tumor has spread to the lymph nodes (N) in the armpits, and whether the tumor has metastasized (M) (i.e. spread to a more distant part of the body). Larger size, nodal spread, and metastasis have a larger stage number and a worse prognosis.
The main stages are:
Stage 0 is a pre-malignant disease or marker (sometimes called DCIS: Ductal Carcinoma in Situ) .
Stages 1–3 are defined as 'early' cancer and potentially curable.
Stage 4 is defined as 'advanced' and/or 'metastatic' cancer and incurable.
Histopathology. Breast cancer is usually, but not always, primarily classified by its histological appearance. Most breast cancers are' derived from the epithelium lining the ducts or lobules, and are classified as mammary ductal carcinoma. Carcinoma in situ is proliferation of cancer cells within the epithelial tissue without invasion of the surrounding tissue. In contrast, invasive carcinoma invades the surrounding tissue.
Grade (Bloom-Richardson grade). When cells become differentiated, they take different shapes and forms to function as part of an organ. Cancerous cells lose that differentiation. In cancer grading, tumor cells are generally classified as well differentiated (low grade), moderately differentiated (intermediate grade), and poorly differentiated (high grade). Poorly differentiated cancers have a worse prognosis.
Receptor status. Cells have receptors on their surface and in their cytoplasm and nucleus. Chemical messengers such as hormones bind to receptors, and this causes changes in the cell. Breast cancer cells may or may not have three important receptors: estrogen receptor (ER), progesterone receptor (PR), and HER2/neu. Cells with none of these receptors are called basal-like or triple negative. ER+ cancer cells depend on estrogen for their growth, so they can be treated with drugs to block estrogen effects (e.g. tamoxifen), and generally have a better prognosis.
Generally, HER2+ had a worse prognosis, however HER2+ cancer cells respond to drugs such as the monoclonal antibody, trastuzumab, (in combination with conventional chemotherapy) and this has improved the prognosis significantly.
DNA microarrays have compared normal cells to breast cancer cells and found differences in hundreds of genes, but the significance of most of those differences is unknown.
Signs and symptoms
Breast cancer showing an inverted nipple, lump, skin dimpling
The first noticeable symptom of breast cancer is typically a lump that feels different from the rest of the breast tissue. More than 80% of breast cancer cases are discovered when the woman feels a lump.[14] By the time a breast lump is noticeable, it has probably been growing for years. The earliest breast cancers are detected by a mammogram.Lumps found in lymph nodes located in the armpits can also indicate breast cancer.
Indications of breast cancer other than a lump may include changes in breast size or shape, skin dimpling, nipple inversion, or spontaneous single-nipple discharge. Pain ("mastodynia") is an unreliable tool in determining the presence or absence of breast cancer, but may be indicative of other breast health issues.
When breast cancer cells invade the dermal lymphatics—small lymph vessels in the skin of the breast—its presentation can resemble skin inflammation and thus is known as inflammatory breast cancer (IBC). Symptoms of inflammatory breast cancer include pain, swelling, warmth and redness throughout the breast, as well as an orange-peel texture to the skin referred to as peau d'orange.
Another reported symptom complex of breast cancer is Paget's disease of the breast. This syndrome presents as eczematoid skin changes such as redness and mild flaking of the nipple skin. As Paget's advances, symptoms may include tingling, itching, increased sensitivity, burning, and pain. There may also be discharge from the nipple. Approximately half of women diagnosed with Paget's also have a lump in the breast.
Occasionally, breast cancer presents as metastatic disease, that is, cancer that has spread beyond the original organ. Metastatic breast cancer will cause symptoms that depend on the location of metastasis. Common sites of metastasis include bone, liver, lung and brain. Unexplained weight loss can occasionally herald an occult breast cancer, as can symptoms of fevers or chills. Bone or joint pains can sometimes be manifestations of metastatic breast cancer, as can jaundice or neurological symptoms. These symptoms are "non-specific", meaning they can also be manifestations of many other illnesses.
Most symptoms of breast disorder do not turn out to represent underlying breast cancer. Benign breast diseases such as mastitis and fibroadenoma of the breast are more common causes of breast disorder symptoms. The appearance of a new symptom should be taken seriously by both patients and their doctors, because of the possibility of an underlying breast cancer at almost any age.
Risk factors
Main article: Risk factors of breast cancer
The primary risk factors that have been identified are sex,age,lack of childbearing or breastfeeding,and higher hormone levels,
In a study published in 1995, well-established risk factors accounted for 47% of cases while only 5% were attributable to hereditary syndromes.
Genetic factors usually increase the risk slightly or moderately; the exception is women and men who are carriers of BRCA mutations. These people have a very high lifetime risk for breast and ovarian cancer, depending on the portion of the proteins where the mutation occurs. Instead of a 12 percent lifetime risk of breast cancer, women with one of these genes has a risk of approximately 60 percent. In more recent years, research has indicated the impact of diet and other behaviors on breast cancer. These additional risk factors include a high-fat diet,
alcohol intake, obesity, and environmental factors such as tobacco use, radiation, endocrine disruptors and shiftwork.
Although the radiation from mammography is a low dose, the cumulative effect can cause cancer.
In addition to the risk factors specified above, demographic and medical risk factors include.
Personal history of breast cancer: A woman who had breast cancer in one breast has an increased risk of getting cancer in her other breast.
Family history: A woman's risk of breast cancer is higher if her mother, sister, or daughter had breast cancer. The risk is higher if her family member got breast cancer before age 40. Having other relatives with breast cancer (in either her mother's or father's family) may also increase a woman's risk.
Certain breast changes: Some women have cells in the breast that look abnormal under a microscope. Having certain types of abnormal cells (atypical hyperplasia and lobular carcinoma in situ ) increases the risk of breast cancer.
Race: Breast cancer is diagnosed more often in women of European ancestry than those of African or Asian ancestry.
A National Cancer Institute (NCI) study of 72,000 women found that those who had a normal body mass index at age 20 and gained weight as they aged had nearly double the risk of developing breast cancer after menopause in comparison to women maintained their weight. The average 60 year-old woman's risk of developing breast cancer by age 65 is about 2 percent; her lifetime risk is 13 percent.
Abortion has not been found to be a risk factor for breast cancer. The breast cancer abortion hypothesis, however, continues to be promoted by some pro-life groups.
The United Kingdom is the member of International Cancer Genome Consortium that is leading efforts to map breast cancer's complete genome.
Pathophysiology
Main article: Carcinogenesis
Overview of signal transduction pathways involved in apoptosis. Mutations leading to loss of apoptosis can lead to tumorigenesis.
Breast cancer, like other cancers, occurs because of an interaction between the environment and a defective gene. Normal cells divide as many times as needed and stop. They attach to other cells and stay in place in tissues. Cells become cancerous when mutations destroy their ability to stop dividing, to attach to other cells and to stay where they belong. When cells divide, their DNA is normally copied with many mistakes. Error-correcting proteins fix those mistakes. The mutations known to cause cancer, such as p53, BRCA1 and BRCA2, occur in the error-correcting mechanisms. These mutations are either inherited or acquired after birth. Presumably, they allow the other mutations, which allow uncontrolled division, lack of attachment, and metastasis to distant organs.
Normal cells will commit cell suicide (apoptosis) when they are no longer needed. Until then, they are protected from cell suicide by several protein clusters and pathways. One of the protective pathways is the PI3K/AKT pathway; another is the RAS/MEK/ERK pathway. Sometimes the genes along these protective pathways are mutated in a way that turns them permanently "on", rendering the cell incapable of committing suicide when it is no longer needed. This is one of the steps that causes cancer in combination with other mutations. Normally, the PTEN protein turns off the PI3K/AKT pathway when the cell is ready for cell suicide. In some breast cancers, the gene for the PTEN protein is mutated, so the PI3K/AKT pathway is stuck in the "on" position, and the cancer cell does not commit suicide.
Mutations that can lead to breast cancer have been experimentally linked to estrogen exposure.
Failure of immune surveillance, the removal of malignant cells throughout one's life by the immune system.
Abnormal growth factor signaling in the interaction between stromal cells and epithelial cells can facilitate malignant cell growth.
People in less-developed countries report lower incidence rates than in developed countries.
In the United States, 10 to 20 percent of patients with breast cancer and patients with ovarian cancer have a first- or second-degree relative with one of these diseases. Mutations in either of two major susceptibility genes, breast cancer susceptibility gene 1 (BRCA1) and breast cancer susceptibility gene 2 (BRCA2), confer a lifetime risk of breast cancer of between 60 and 85 percent and a lifetime risk of ovarian cancer of between 15 and 40 percent. However, mutations in these genes account for only 2 to 3 percent of all breast cancers.
Diagnosis This section does not cite any references or sources.
Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (October 2007)
While screening techniques (which are further discussed below) are useful in determining the possibility of cancer, a further testing is necessary to confirm whether a lump detected on screening is cancer, as opposed to a benign alternative such as a simple cyst.
In a clinical setting, breast cancer is commonly diagnosed using a "triple test" of clinical breast examination (breast examination by a trained medical practitioner), mammography, and fine needle aspiration cytology. Both mammography and clinical breast exam, also used for screening, can indicate an approximate likelihood that a lump is cancer, and may also identify any other lesions. Fine Needle Aspiration and Cytology (FNAC), which may be done in a GP's office using local anaesthetic if required, involves attempting to extract a small portion of fluid from the lump. Clear fluid makes the lump highly unlikely to be cancerous, but bloody fluid may be sent off for inspection under a microscope for cancerous cells. Together, these three tools can be used to diagnose breast cancer with a good degree of accuracy.
Other options for biopsy include core biopsy, where a section of the breast lump is removed, and an excisional biopsy, where the entire lump is removed.
In addition vacuum-assisted breast biopsy (VAB) may help diagnose breast cancer among patients with a mammographically detected breast in women according to a systematic review .[48] In this study, summary estimates for vacuum assisted breast biopsy in diagnosis of breast cancer were as follows sensitivity was 98.1% with 95% CI = 0.972-0.987 and specificity was 100% with 95% CI = 0.997-0.999. However underestimate rates of atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) were 20.9% with 95% CI =0.177-0.245 and 11.2% with 95% CI = 0.098-0.128 respectively.
Excised human breast tissue, showing an irregular, dense, white stellate area of cancer 2 cm in diameter, within yellow fatty tissue.
Micrograph showing a lymph node invaded by ductal breast carcinoma and with extranodal extension of tumour.
Neuropilin-2 expression in normal breast and breast carcinoma tissue.
Lymph nodes which drain the breast
F-18 FDG PET/CT: Metastasis of a mamma carcinoma in the right scapula
Screening
Main article: Breast cancer screening
Breast cancer screening refers to testing otherwise-healthy women for breast cancer in an attempt to achieve an earlier diagnosis. The assumption is that early detection will improve outcomes. A number of screening test have been employed including: clinical and self breast exams, mammography, genetic screening, ultrasound, and magnetic resonance imaging.
A clinical or self breast exam involves feeling the breast for lumps or other abnormalities. Research evidence does not support the effectiveness of either type of breast exam, because by the time a lump is large enough to be found it is likely to have been growing for several years and will soon be large enough to be found without an exam.
Mammographic screening for breast cancer uses x-rays to examine the breast for any uncharacteristic masses or lumps. The Cochrane collaboration in 2009 concluded that mammograms reduce mortality from breast cancer by 15 percent but also result in unnecessary surgery and anxiety, resulting in their view that mammography screening may do more harm than good.
Many national organizations recommend regular mammography, nevertheless. For the average woman, the U.S. Preventive Services Task Force recommends mammography every two years in women between the ages of 50 and 74.
The Task Force points out that in addition to unnecessary surgery and anxiety, the risks of more frequent mammograms include a small but significant increase in breast cancer induced by radiation.
In women at high risk, such as those with a strong family history of cancer, mammography screening is recommended at an earlier age and additional testing may include genetic screening that tests for the BRCA genes and / or magnetic resonance imaging.
Treatment
Main article: Breast cancer treatment
Breast cancer is sometimes treated first with surgery, and then with chemotherapy, radiation, or both. Treatments are given with increasing aggressiveness according to the prognosis and risk of recurrence.
Stage 1 cancers (and DCIS) have an excellent prognosis and are generally treated with lumpectomy with or without chemotherapy or radiation.
Although the aggressive HER2+ cancers should also be treated with the trastuzumab (Herceptin) regime.
Stage 2 and 3 cancers with a progressively poorer prognosis and greater risk of recurrence are generally treated with surgery (lumpectomy or mastectomy with or without lymph node removal), radiation (sometimes) and chemotherapy (plus trastuzumab for HER2+ cancers).
Stage 4, metastatic cancer, (i.e. spread to distant sites) is not curable and is managed by various combinations of all treatments from surgery, radiation, chemotherapy and targeted therapies. These treatments increase the median survival time of stage 4 breast cancer by about 6 months.
Medications
Drugs used after and in addition to surgery are called adjuvant therapy. Chemotherapy prior to surgery is called neo-adjuvant therapy. There are currently 3 main groups of medications used for adjuvant breast cancer treatment . Hormone Blocking Therapy, Chemotherapy Monoclonal Antibodies One or all of these groups can be used.
Hormone Blocking Therapy: Some breast cancers require estrogen to continue growing. They can be identified by the presence of estrogen receptors (ER+) and progesterone receptors (PR+) on their surface (sometimes referred to together as hormone receptors, HR+). These ER+ cancers can be treated with drugs that either block the receptors, such as tamoxifen, or alternatively block the production of estrogen, such as the aromatase inhibitor, anastrozole (Arimidex).
Chemotherapy: Usually used for stage 1-4 disease. They are given in combinations. One of the most common treatments is cyclophosphamide plus doxorubicin (Adriamycin), known as AC; these drugs damage DNA in the cancer, but also in fast-growing normal cells where they cause serious side effects. Damage to the heart muscle is the most dangerous complication of doxorubicin. Sometimes a taxane drug, such as docetaxel, is added, and the regime is then known as CAT; taxane attacks the microtubules in cancer cells. Another common treatment, which produces equivalent results, is cyclophosphamide, methotrexate, and fluorouracil (CMF). (Chemotherapy can literally refer to any drug, but it is usually used to refer to traditional non-hormone treatments for cancer.)
Monoclonal antibodies: A relatively recent and very exciting development in HER2+ breast cancer treatment. Cancer cells have a receptor called HER2 on their surface. This receptor is normally stimulated by a growth factor which causes the cell to divide, however in the absence of the growth factor, the cell will normally stop growing. In approx 20% of invasive breast cancers, the HER2 receptor is stuck in the "on" position. The cell divides without stopping, producing an aggressive form of cancer. Trastuzumab (Herceptin), a monoclonal antibody to HER2, has dramatically improved the 5yr disease free survival of 'early' (stages 1–3) HER2+ breast cancers to about 87%.
Trastuzumab, however, is expensive, and approx 2% of patients suffer significant heart damage; it is otherwise well tolerated with far milder side effects than conventional chemotherapy.
Other monoclonal antibodies are also being trialled.
Finally, a recent article has claimed that Aspirin may reduce mortality from breast cancer.
Radiation
Radiotherapy is given after surgery to the region of the tumor bed, to destroy microscopic tumors that may have escaped surgery. It may also have a beneficial effect on tumour microenvironment.
Radiation therapy can be delivered as external beam radiotherapy or as brachytherapy (internal radiotherapy). Conventionally radiotherapy is given after the operation for breast cancer. Radiation can also be given, arguably more efficiently, at the time of operation on the breast cancer- intraoperatively. The largest randomised trial to test this approach was the TARGIT-A Trial which found that targeted intraoperative radiotherapy was equally effective at 4-years as the usual several weeks' of whole breast external beam radiotherapy .
Radiation can reduce the risk of recurrence by 50-66% (1/2 - 2/3rds reduction of risk) when delivered in the correct dose
and is considered essential when breast cancer is treated by removing only the lump (Lumpectomy or Wide local excision)
Prognosis
A prognosis is a prediction of outcome, usually the probability of death (or survival), and the probability of progression-free survival (PFS) or disease-free survival (DFS). These predictions are based on experience with breast cancer patients with similar classification. A prognosis is an estimate, as patients with the same classification will survive a different amount of time, and classifications are not always precise. Survival is usually calculated as an average number of months (or years) that 50% of patients survive, or the percentage of patients that are alive after 1, 5, 15 and 20 years. Prognosis is important for treatment decisions because patients with a good prognosis are usually offered less invasive treatments, such as lumpectomy and radiation or hormone therapy, while patients with poor prognosis are usually offered more aggressive treatment, such as more extensive mastectomy and one or more chemotherapy drugs.
Prognostic factors include staging, (i.e., tumor size, location, grade, whether disease has traveled to other parts of the body), recurrence of the disease, and age of patient.Stage is the most important, as it takes into consideration size, local involvement, lymph node status and whether metastatic disease is present. The higher the stage at diagnosis, the worse the prognosis. The stage is raised by the invasiveness of disease to lymph nodes, chest wall, skin or beyond, and the aggressiveness of the cancer cells. The stage is lowered by the presence of cancer-free zones and close-to-normal cell behaviour (grading). Size is not a factor in staging unless the cancer is invasive. For example, Ductal Carcinoma In Situ (DCIS) involving the entire breast will still be stage zero and consequently an excellent prognosis with a 10yr disease free survival of about 98%.
Grading is based on how biopsied, cultured cells behave. The closer to normal cancer cells are, the slower their growth and the better the prognosis. If cells are not well differentiated, they will appear immature, will divide more rapidly, and will tend to spread. Well differentiated is given a grade of 1, moderate is grade 2, while poor or undifferentiated is given a higher grade of 3 or 4 (depending upon the scale used).
Younger women tend to have a poorer prognosis than post-menopausal women due to several factors. Their breasts are active with their cycles, they may be nursing infants, and may be unaware of changes in their breasts. Therefore, younger women are usually at a more advanced stage when diagnosed. There may also be biologic factors contributing to a higher risk of disease recurrence for younger women with breast cancer.
The presence of estrogen and progesterone receptors in the cancer cell is important in guiding treatment. Those who do not test positive for these specific receptors will not be able to respond to hormone therapy, and this can affect their chance of survival depending upon what treatment options remain, the exact type of the cancer, and how advanced the disease is.
In addition to hormone receptors, there are other cell surface proteins that may affect prognosis and treatment. HER2 status directs the course of treatment. Patients whose cancer cells are positive for HER2 have more aggressive disease and may be treated with the 'targeted therapy', trastuzumab (Herceptin), a monoclonal antibody that targets this protein and improves the prognosis significantly. Tumors overexpressing the Wnt signaling pathway co-receptor low-density lipoprotein receptor-related protein 6 (LRP6) may represent a distinct subtype of breast cancer and a potential treatment target.
Psychological aspects
The emotional impact of cancer diagnosis, symptoms, treatment, and related issues can be severe. Most larger hospitals are associated with cancer support groups which provide a supportive environment to help patients cope and gain perspective from cancer survivors. Online cancer support groups are also very beneficial to cancer patients, especially in dealing with uncertainty and body-image problems inherent in cancer treatment.
Not all breast cancer patients experience their illness in the same manner. Factors such as age can have a significant impact on the way a patient copes with a breast cancer diagnosis. Premenopausal women with estrogen-receptor positive breast cancer must confront the issues of early menopause induced by many of the chemotherapy regimens used to treat their breast cancer, especially those that use hormones to counteract ovarian function.
On the other hand, a recent study conducted by researchers at the College of Public Health of the University of Georgia showed that older women may face a more difficult recovery from breast cancer than their younger counterparts.
As the incidence of breast cancer in women over 50 rises and survival rates increase, breast cancer is increasingly becoming a geriatric issue that warrants both further research and the expansion of specialized cancer support services tailored for specific age groups.
Epidemiology
Age-standardized death from breast cancer per 100,000 inhabitants in 2004. no data
less than 2
2-4
4-6
6-8
8-10
10-12
12-14
14-16
16-18
18-20
20-22
more than 22
Worldwide, breast cancer is the most common cancer in women, after skin cancer, representing 16% of all female cancers. The rate is more than twice that of colorectal cancer and cervical cancer and about three times that of lung cancer.Mortality worldwide is 25% greater than that of lung cancer in women. In 2004, breast cancer caused 519,000 deaths worldwide (7% of cancer deaths; almost 1% of all deaths). The number of cases worldwide has significantly increased since the 1970s, a phenomenon partly attributed to the modern lifestyles.
The incidence of breast cancer varies greatly around the world: it is lowest in less-developed countries and greatest in the more-developed countries. In the twelve world regions, the annual age-standardized incidence rates per 100,000 women are as follows: in Eastern Asia, 18; South Central Asia, 22; sub-Saharan Africa, 22; South-Eastern Asia, 26; North Africa and Western Asia, 28; South and Central America, 42; Eastern Europe, 49; Southern Europe, 56; Northern Europe, 73; Oceania, 74; Western Europe, 78; and in North America, 90.
Breast cancer is strongly related to age with only 5% of all breast cancers occur in women under 40 years old. However, it can occur in younger women.
United States
The lifetime risk for breast cancer in the United States is usually given as 1 in 8 (12.5%) with a 1 in 35 (3%) chance of death. A recent analysis however has called this estimate into question when it found a risk of only 6% in healthy women.
The United States has the highest annual incidence rates of breast cancer in the world; 128.6 per 100,000 in whites and 112.6 per 100,000 among African Americans. It is the second-most common cancer (after skin cancer) and the second-most common cause of cancer death (after lung cancer). In 2007, breast cancer was expected to cause 40,910 deaths in the US (7% of cancer deaths; almost 2% of all deaths). This figure includes 450-500 annual deaths among men out of 2000 cancer cases.
In the US, both incidence and death rates for breast cancer have been declining in the last few years in Native Americans and Alaskan Natives. Nevertheless, a US study conducted in 2005 indicated that breast cancer remains the most feared disease,even though heart disease is a much more common cause of death among women. Many doctors say that women exaggerate their risk of breast cancer.
Cancer occurence in females in the United States. Breast cancer is seen in light green at left. By mortality
Racial disparities
Several studies have found that black women in the U.S. are more likely to die from breast cancer even though white women are more likely to be diagnosed with the disease. Even after diagnosis, black women are less likely to get treatment compared to white women. Scholars have advanced several theories for the disparities, including inadequate access to screening, reduced availability of the most advanced surgical and medical techniques, or some biological characteristic of the disease in the African American population. Some studies suggest that the racial disparity in breast cancer outcomes may reflect cultural biases more than biological disease differences. However, the lack of diversity in clinical trials for breast cancer treatment may contribute to these disparities, with recent research indicating that black women are more likely to have estrogen receptor negative breast cancers, which are not responsive to hormone treatments that are effective for most white women.Research is currently ongoing to define the contribution of both biological and cultural factors.
UK
45,000 cases diagnosed and 12,500 deaths per annum. 60% of cases are treated with Tamoxifen, of these the drug becomes ineffective in 35%.
Developing countries
As developing countries grow and adopt Western culture they also accumulate more disease that has arisen from Western culture and its habits (fat/alcohol intake, smoking, exposure to oral contraceptives, the changing patterns of childbearing and breastfeeding, low parity). For instance, as South America has developed so has the amount of breast cancer. Breast cancer in less developed countries, such as those in South America, is a major public health issue. It is a leading cause of cancer-related deaths in women in countries such as Argentina, Uruguay, and Brazil. The expected numbers of new cases and deaths due to breast cancer in South America for the year 2001 are approximately 70,000 and 30,000, respectively. However, because of a lack of funding and resources, treatment is not always available to those suffering with breast cancer.
History
Breast cancer surgery in the 18th century
Breast cancer may be one of the oldest known forms of cancerous tumors in humans. The oldest description of cancer was discovered in Egypt and dates back to approximately 1600 BC. The Edwin Smith Papyrus describes 8 cases of tumors or ulcers of the breast that were treated by cauterization. The writing says about the disease, "There is no treatment. For centuries, physicians described similar cases in their practises, with the same conclusion. It was not until doctors achieved greater understanding of the circulatory system in the 17th century that they could establish a link between breast cancer and the lymph nodes in the armpit. The French surgeon Jean Louis Petit (1674–1750) and later the Scottish surgeon Benjamin Bell (1749–1806) were the first to remove the lymph nodes, breast tissue, and underlying chest muscle. Their successful work was carried on by William Stewart Halsted who started performing mastectomies in 1882. The Halsted radical mastectomy often involved removing both breasts, associated lymph nodes, and the underlying chest muscles. This often led to long-term pain and disability, but was seen as necessary in order to prevent the cancer from recurring.Radical mastectomies remained the standard until the 1970s, when a new understanding of metastasis led to perceiving cancer as a systemic illness as well as a localized one, and more sparing procedures were developed that proved equally effective.
The French surgeon Bernard Peyrilhe (1737–1804) realized the first experimental transmission of cancer by injecting extracts of breast cancer into an animal.
Prominent women who died of breast cancer include Empress Theodora, wife of Justinian; Anne of Austria, mother of Louis XIV of France; Mary Washington, mother of George, and Rachel Carson, the environmentalist.
The first case-controlled study on breast cancer epidemiology was done by Janet Lane-Claypon, who published a comparative study in 1926 of 500 breast cancer cases and 500 control patients of the same background and lifestyle for the British Ministry of Health.
Society and culture
A pink ribbon, the universal symbol of breast cancer awareness.
The widespread acceptance of second opinions before surgery, less invasive surgical procedures, support groups, and other advances in patient care have stemmed, in part, from the breast cancer advocacy movement.
October is recognized as National Breast Cancer Awareness Month by the media as well as survivors, family and friends of survivors and/or victims of the disease. A pink ribbon is worn to recognize the struggle that sufferers face when battling with the cancer. On the meaning of this, see Semiotics of breast cancer pink ribbon.
The patron saint of breast cancer is Agatha of Sicily.
In the fall of 1991, Susan G. Komen for the Cure handed out pink ribbons to participants in its New York City race for breast cancer survivors.
The pink and blue ribbon was designed in 1996 by Nancy Nick, President and Founder of the John W. Nick Foundation to bring awareness that "Men Get Breast Cancer Too!
In 2009 the male breast cancer advocacy groups Out of the Shadow of Pink, A Man's Pink and the Brandon Greening Foundation for Breast Cancer in Men joined together to globally establish the third week of October as "Male Breast Cancer Awareness Week"
In the first quarter of 2009, Anthony L. May the President and Founder of Men For A Cause, United Against Breast Cancer created the very symbolic Official Breast Cancer Awareness Flag to advocate year around breast cancer awareness.
Art
Possible breast cancer signs in historical paintings have been repeatedly discussed in medical literature. A typical lump, differences in breast size or shape and the peau d'orange can be found for example in works by Raphael, Rembrandt and Rubens. However if the visible changes are really dealing with breast cancer can not be proved and was therefore doubted.Examples of breast cancer signs in art
Raffaelo Sanzio (1483-1520): „Portrait of a young woman“ („La Fornarina“)
Peter Paul Rubens (1577–1640): „The Three Graces“
Rembrandt van Rijn (1606–1669): „Bathseba with David's Letter“
Details
Cell lines for research A considerable part of the current knowledge on breast carcinomas is based on in vivo and in vitro studies performed with breast cancer cell (BCC) lines. These provide an unlimited source of homogenous self-replicating material, free of contaminating stromal cells, and often easily cultured in simple standard media. The first line described, BT-20, was established in 1958. Since then, and despite sustained work in this area, the number of permanent lines obtained has been strikingly low (about 100). Indeed, attempts to culture BCC from primary tumors have been largely unsuccessful. This poor efficiency was often due to technical difficulties associated with the extraction of viable tumor cells from their surrounding stroma. Most of the available BCC lines issued from metastatic tumors, mainly from pleural effusions. Effusions provided generally large numbers of dissociated, viable tumor cells with little or no contamination by fibroblasts and other tumor stroma cells. Many of the currently used BCC lines were established in the late 1970s. A very few of them, namely MCF-7, T-47D, and MDA-MB-231, account for more than two-thirds of all abstracts reporting studies on mentioned BCC lines, as concluded from a Medline-based survey.
Treatments are constantly evaluated in randomized, controlled trials, to evaluate and compare individual drugs, combinations of drugs, and surgical and radiation techniques. The latest research is reported annually at scientific meetings such as that of the American Society of Clinical Oncology, San Antonio Breast Cancer Symposium, and the St. Gallen Oncology Conference in St. Gallen, Switzerland. These studies are reviewed by professional societies and other organizations, and formulated into guidelines for specific treatment groups and risk category.
List of cell lines
Mainly based on Lacroix and Leclercq (2004). For more data on the nature of TP53 mutations in breast cancer cell lines, see Lacroix et al. (2006).
This is an incomplete list, which may never be able to satisfy particular standards for completeness. You can help by expanding it with reliably sourced entries.Cell line Primary tumor Origin of cells Estrogen receptors Progesterone receptors ERBB2 amplification Mutated TP53 Tumorigenic in mice Reference
600MPE Invasive ductal carcinoma + - AU565 Adenocarcinoma - - + -
BT-20 Invasive ductal carcinoma Primary No No No Yes Yes
BT-474 Invasive ductal carcinoma Primary Yes Yes Yes Yes Yes
BT-483 Invasive ductal carcinoma + + -
BT-549 Invasive ductal carcinoma - - +
Evsa-T Invasive ductal carcinoma, mucin-producing, signet-ring type Metastasis (ascites) No Yes ? Yes ?
Hs578T Carcinosarcoma Primary No No No Yes No
MCF-7 Invasive ductal carcinoma Metastasis (pleural effusion) Yes
Yes No (wild-type) Yes (with estrogen supplementation)
MDA-MB-231 Invasive ductal carcinoma Metastasis (pleural effusion) No No No Yes Yes
SK-BR-3 Invasive ductal carcinoma Metastasis (pleural effusion) No No Yes Yes No
T-47D Invasive ductal carcinoma Metastasis (pleural effusion) Yes Yes No Yes Yes (with estrogen supplementation)
See also
Male breast cancer
Semiotics of breast cancer pink ribbon
List of notable breast cancer patients according to occupation
List of notable breast cancer patients according to survival status
List of breast carcinogenic substances
Mammary tumor for breast cancer in other animals
Breast reconstruction
External beam radiotherapy
Brachytherapy
Alcohol and cancer
Mammography Quality Standards Act
National Breast Cancer Coalition
National Comprehensive Cancer Network
Breast Cancer Action
Breakthrough Breast Cancer
Living Beyond Breast Cancer
International Agency for Research on Cancer
Susan G. Komen for the Cure
Breast Cancer Network of Strength
Your Disease Risk
Sentinel lymph node Biopsy, a new technique for staging the axilla
Kara Magsanoc-Alikpala Philippine activist against breast cancer.