Cancer Corner

Cancer

2007-09-05T18:22:00.000-07:00

Wear a pink ribbon in support of the all of those who have struggled and battled against breast cancer, and to bring awareness and rememberance to our minds.

Cancer may affect people at all ages, but risk for the more common varieties tends to increase with age. Cancer causes about 13% of all deaths.

Nearly all cancers are caused by abnormalities in the genetic material of the transformed cells. These abnormalities may be due to the effects of carcinogens, such as tobacco smoke, radiation, chemicals, or infectious agents. Other cancer-promoting genetic abnormalities may be randomly acquired through errors in DNA replication, or are inherited, and thus present in all cells from birth. Complex interactions between carcinogens and the host genome may explain why only some patients get cancer after exposure to a known carcinogen. New aspects of the genetics of cancer pathogenesis, such as DNA methylation, and microRNAs are increasingly being recognized as important.

Genetic abnormalities found in cancer typically affect two general classes of genes. Cancer-promoting oncogenes are often activated in cancer cells, giving those cells new properties, such as hyperactive growth and division, protection against programmed cell death, loss of respect for normal tissue boundaries, and the ability to become established in diverse tissue environments. Tumor suppressor genes are often inactivated in cancer cells, resulting in the loss of normal functions in those cells, such as accurate DNA replication, control over the cell cycle, orientation and adhesion within tissues, and interaction with protective cells of the immune system.

Cancer is usually classified according to the tissue from which the cancerous cells originate, as well as the normal cell type they most resemble. These are location and histology, respectively. A definitive diagnosis usually requires the histologic examination of a tissue biopsy specimen by a pathologist, although the initial indication of malignancy can be symptoms or radiographic imaging abnormalities. Most cancers can be treated and some cured, depending on the specific type, location, and stage. Once diagnosed, cancer is usually treated with a combination of surgery, chemotherapy and radiotherapy. As research develops, treatments are becoming more specific for different varieties of cancer. There has been significant progress in the development of targeted therapy drugs that act specifically on detectable molecular abnormalities in certain tumors, and which minimize damage to normal cells. The prognosis of cancer patients is most influenced by the type of cancer, as well as the stage, or extent of the disease. In addition, histologic grading and the presence of specific molecular markers can also be useful in establishing prognosis, as well as in determining individual treatments.

Classification
Nomenclature
The following closely related terms may be used to designate abnormal growths:

Neoplasm: A scientific term which refers to an abnormal proliferation of
genetically altered cells.
Malignant neoplasm: Synonymous with cancer.
Tumor: Broadly defined, can be any swelling or mass. However, the vast majority of entities referred to as 'tumors' in common usage are in fact neoplasms. Specifically, a tumor is a solid neoplasm; some neoplasms, such as cancers of the blood, are not solid.
Benign tumor: A tumor (solid neoplasm) that has self-limiting growth and does not invade other tissues nor metastasize. Usually not cancerous.
Pre-malignancy: A non-invasive neoplasm that may not form an obvious mass, but has the potential to progress to cancer if left untreated. Pre-malignant neoplasms may show distinctive microscopic changes such as dysplasia or atypia.

Cancers are classified by the type of cell that resembles the tumor and, therefore, the tissue presumed to be the origin of the tumor. Examples of general categories include:

Carcinoma: Malignant tumors derived from epithelial cells. This group
represents the most common cancers, including the common forms of breast,
prostate, lung and colon cancer.
Sarcoma: Malignant tumors derived from
connective tissue, or mesenchymal cells
Lymphoma and leukemia:
Malignancies derived from hematopoetic (blood-forming) cells
Germ cell tumor: Tumors derived from totipotent cells. In adults most often found in the testicle and ovary; in fetuses, babies, and young children most often found on
the body midline, particularly at the tip of the tailbone; in horses most often
found at the poll (base of the skull).
Blastic tumor: A tumor (usually malignant) which resembles an immature or embryonic tissue. Many of these tumors are most common in children

Malignant tumors are usually named using the Latin or Greek root of the organ of origin as a prefix and the above category name as the suffix. For instance, a malignant tumor of the liver is called hepatocarcinoma; a malignant tumor of the fat cells is called liposarcoma. For common cancers, the English organ name is used. For instance, the most common type of breast cancer is called ductal carcinoma of the breast or mammary ductal carcinoma. Here, the adjective ductal refers to the appearance of the cancer under the microscope, resembling normal breast ducts.

Benign tumors are named using -oma as a suffix with the organ name as the root. For instance, a benign tumor of the smooth muscle of the uterus is called leiomyoma (the common name of this frequent tumor is fibroid). However, some cancers also use this prefix for historical reasons, examples being melanoma and seminoma.

Adult cancers
In the U.S. and other developed countries, cancer is presently responsible for about 25% of all deaths.

On a yearly basis, 0.5% of the population is diagnosed with cancer. The statistics below are for adults in the United States, and will vary substantially in other countries:

Male
most common........................cause of death
prostate cancer (33%)...............lung cancer (31%)
lung cancer (13%).......................prostate cancer (10%)
colorectal cancer (10%).............colorectal cancer (10%)
bladder cancer (7%)...................pancreatic cancer (5%)
cutaneous melanoma (5%)........leukemia (4%)

Female
most common..........................cause of death
breast cancer (32%)....................lung cancer (27%)
lung cancer (12%)........................breast cancer (15%)
colorectal cancer (11%)...............colorectal cancer (10%)
endometrial cancer (6%)............ovarian cancer (6%)
non-Hodgkin lymphoma (4%)...pancreatic cancer (6%)

Childhood cancers
Cancer can also occur in young children and adolescents, but it is rare. Some studies have concluded that pediatric cancers, especially leukemia, are on an upward trend.

The age of peak incidence of cancer in children occurs during the first year of life. Leukemia (usually ALL) is the most common infant malignancy (30%), followed by the central nervous system cancers and neuroblastoma. The remainder consists of Wilms' tumor, lymphomas, rhabdomyosarcoma (arising from muscle), retinoblastoma, osteosarcoma and Ewing's sarcoma. Teratoma is the most common tumor in this age group, but most teratomas are surgically removed while they are still benign.

Female and male infants have essentially the same overall cancer incidence rates, but white infants have substantially higher cancer rates than black infants for most cancer types. Relative survival for infants is very good for neuroblastoma, Wilms' tumor and retinoblastoma, and fairly good (80%) for leukemia, but not for most other types of cancer.

Causes and pathophysiology

Cancer is a diverse class of diseases which differ widely in their causes and biology. The common thread in all known cancers is the acquisition of abnormalities in the genetic material of the cancer cell and its progeny. Research into the pathogenesis of cancer can be divided into three broad areas of focus. The first area of research focuses on the agents and events which cause or facilitate genetic changes in cells destined to become cancer. Second, it is important to uncover the precise nature of the genetic damage, and the genes which are affected by it. The third focus is on the consequences of those genetic changes on the biology of the cell, both in generating the defining properties of a cancer cell, and in facilitating additional genetic events, leading to further progression of the cancer.

Inciting events
Chemical carcinogens
Cancer pathogenesis is traceable back to DNA mutations that impact cell growth and metastasis. Substances that cause DNA mutations are known as mutagens, and mutagens that cause cancers are known as carcinogens. Particular substances have been linked to specific types of cancer. Tobacco smoking is associated with lung cancer and bladder cancer. Prolonged exposure to asbestos fibers is associated with mesothelioma.

Many mutagens are also carcinogens, but some carcinogens are not mutagens. Alcohol is an example of a chemical carcinogen that is not a mutagens. Such chemicals are thought to promote cancers through their stimulating effect on the rate of cell mitosis. Faster rates of mitosis leaves less time for repair enzymes to repair damaged DNA during DNA replication, increasing the likelihood of a genetic mistake. A mistake made during mitosis can lead to the daughter cells receiving the wrong number of chromosomes, see aneuploidy above.

Decades of research have demonstrated the strong association between tobacco use and cancers of many sites, making it perhaps the most important human carcinogen. Hundreds of epidemiological studies have confirmed this association. Further support comes from the fact that lung cancer death rates in the United States have mirrored smoking patterns, with increases in smoking followed by dramatic increases in lung cancer death rates and, more recently, decreases in smoking followed by decreases in lung cancer death rates in men.

Electromagnetic radiation
Prolonged exposure to radiation, particularly ultraviolet radiation from the sun, leads to melanoma and other skin malignancies.

Infectious diseases
Furthermore, many cancers originate from a viral infection; this is especially true in animals such as birds, but also in humans, as viruses are responsible for 15% of human cancers worldwide. The main viruses associated with human cancers are human papillomavirus, hepatitis B and hepatitis C virus, Epstein-Barr virus, and human T-lymphotropic virus. Experimental and epidemiological data imply a causative role for viruses and they appear to be the second most important risk factor for cancer development in humans, exceeded only by tobacco usage. The mode of virally-induced tumors can be divided into two, acutely-transforming or slowly-transforming. In acutely transforming viruses, the viral particles carry a gene that encodes for an overactive oncogene called viral-oncogene (v-onc), and the infected cell is transformed as soon as v-onc is expressed. In contrast, in slowly-transforming viruses, the virus genome is inserted, especially as viral genome insertion is an obligatory part of retroviruses, near a proto-oncogene in the host genome. The viral promoter or other transcription regulation elements in turn cause overexpression of that proto-oncogene, which in turn induces uncontrolled cellular proliferation. Because viral genome insertion is not specific to proto-oncogenes and the chance of insertion near that proto-oncogene is low, slowly-transforming viruses have very long tumor latency compared to acutely-transforming viruses, which already carry the viral oncogene.

Hepatitis viruses, including hepatitis B and hepatitis C, can induce a chronic viral infection that leads to liver cancer in 0.47% of hepatitis B patients per year (especially in Asia, less so in North America), and in 1.4% of hepatitis C carriers per year. Liver cirrhosis, whether from chronic viral hepatitis infection or alcoholism, is associated with the development of liver cancer, and the combination of cirrhosis and viral hepatitis presents the highest risk of liver cancer development. Worldwide, liver cancer is one of the most common, and most deadly, cancers due to a huge burden of viral hepatitis transmission and disease.

Advances in cancer research have made a vaccine designed to prevent cancer available. In 2006, the US FDA approved a human papilloma virus vaccine, called Gardasil®. The vaccine protects against four HPV types, which together cause 70% of cervical cancers and 90% of genital warts. In March 2007, the US CDC Advisory Committee on Immunization Practices (ACIP) officially recommended that females aged 11-12 receive the vaccine, and indicated that females as young as age 9 and as old as age 26 are also candidates for immunization.

In addition to viruses, researchers have noted a connection between bacteria and certain cancers. The most prominent example is the link between chronic infection of the wall of the stomach with Helicobacter pylori and gastric cancer.

Hormonal imbalances
Some hormones can act in a similar manner to non-mutagenic carcinogens in that they may stimulate excessive cell growth. A well-established example is the role of hyperestrogenic states in promoting endometrial cancer. There is also a growing body of research that correlates cancer incidence with the lower levels of melatonin produced in the body when people spend more time in bright-light conditions, as happens typically in the well-lit nighttime environments of the more developed countries. This effect is compounded in people who sleep fewer hours and in people who work at night, two groups that are known to have higher cancer rates.
PMID: 16084719

Immune system dysfunction
HIV is associated with a number of malignancies, including Kaposi's sarcoma, non-Hodgkin's lymphoma, and HPV-associated malignancies such as anal cancer and cervical cancer. AIDS-defining illnesses have long included these diagnoses. The increased incidence of malignancies in HIV patients points to the breakdown of immune surveillance as a possible etiology of cancer. Certain other immune deficiency states (e.g. common variable immunodeficiency and IgA deficiency) are associated with increased risk of malignancy.

Heredity
Most forms of cancer are "sporadic", and have no basis in heredity. There are, however, a number of recognised syndromes of cancer with a hereditary component, often a defective tumor suppressor allele. Famous examples are:

certain inherited mutations in the genes BRCA1 and BRCA2 are associated with an
elevated risk of breast cancer and ovarian cancer
tumors of various endocrine organs in multiple endocrine neoplasia (MEN types 1, 2a, 2b)
Li-Fraumeni syndrome (various tumors such as osteosarcoma, breast cancer,
soft-tissue sarcoma, brain tumors) due to mutations of p53
Turcot syndrome (brain tumors and colonic polyposis)
Familial adenomatous polyposis an inherited mutation of the APC gene that leads to early onset of colon carcinoma.
Hereditary nonpolyposis colorectal cancer (HNPCC, also known as Lynch
syndrome) can include familial cases of colon cancer, uterine cancer, gastric
cancer, and ovarian cancer, without a preponderance of colon polyps.
Retinoblastoma, when occurring in young children, is due to a hereditary
mutation in the retinoblastoma gene.
Down syndrome patients, who have an extra chromosome 21, are known to develop malignancies such as leukemia and testicular cancer, though the reasons for this difference are not well understood.

Other causes
A few types of cancer in non-humans have been found to be caused by the tumor cells themselves. This phenomenon is seen in Sticker's sarcoma, also known as canine transmissible venereal tumor. The closest known analogue to this in humans is individuals who have developed cancer from tumors hiding inside organ transplants.

Cancer genetics
Cancer is fundamentally a genetic disease. In order for a normal cell to tranform into a cancer cell, genes which regulate cell growth and differentiation must be altered. Genetic changes can occur at many levels, from gain or loss of entire chromosomes to a mutation affecting a single DNA nucleotide. There are two broad categories of genes which are affected by these changes. Oncogenes may be normal genes which are expressed at inappropriately high levels, or altered genes which have novel properties. In either case, expression of these genes promotes the malignant phenotype of cancer cells. Tumor suppressor genes are genes which inhibit cell division, survival, or other properties of cancer cells. Tumor suppressor genes are often disabled by cancer-promoting genetic changes. Typically, changes in many genes are required to transform a normal cell into a cancer cell.

Types of genetic abnormality
There is a diverse classification scheme for the various genomic changes which may contribute to the generation of cancer cells. Most of these changes are mutations, or changes in the nucleotide sequence of genomic DNA. Aneuploidy, the presence of an abnormal number of chromomes, is one genomic change which is not a mutation, and may involve either gain or loss of one or more chromosomes through errors in mitosis.

Large-scale mutations involve the deletion or gain of a portion of a chromosome. Genomic amplification occurs when a cell gains many copies (often 20 or more) of a small chromosomal locus, usually containing one or more oncogenes and adjacent genetic material. Translocation occurs when two separate chromosomal regions become abnormally fused, often at a characteristic location. A well-known example of this is the Philadelphia chromosome, or translocation of chromosomes 9 and 22, which occurs in chronic myelogenous leukemia, and results in production of the BCR-abl fusion protein, an oncogenic tyrosine kinase.

Small-scale mutations include point mutations, deletions, and insertions, which may occur in the promoter of a gene and affect its expression, or may occur in the gene's coding sequence and alter the function or stability of its protein product. Disruption of a single gene may also result from integration of genomic material from a DNA virus or retrovirus, and such an event may also result in the expression of viral oncogenes in the affected cell and its descendants.

Epigenetic changes are changes which do not affect chromosomal number or DNA sequence, but which can be passed on through generations of cell division, and thus may play a role in cancer. Known mechanisms of epigenetic change include DNA methylation, and methylation or acetylation of histone proteins bound to chromosomal DNA at specific locations.

Oncogenes
Oncogenes promote cell growth through a variety of ways. Many can produce hormones, a "chemical messenger" between cells which encourage mitosis, the effect of which depends on the signal transduction of the receiving tissue or cells. In other words, when a hormone receptor on a recipient cell is stimulated, the signal is conducted from the surface of the cell to the cell nucleus to effect some change in gene transcription regulation at the nuclear level. Some oncogenes are part of the signal transduction system itself, or the signal receptors in cells and tissues themselves, thus controlling the sensitivity to such hormones. Oncogenes often produce mitogens, or are involved in transcription of DNA in protein synthesis, which creates the proteins and enzymes responsible for producing the products and biochemicals cells use and interact with.

Mutations in proto-oncogenes, which are the normally quiescent counterparts of oncogenes, can modify their expression and function, increasing the amount or activity of the product protein. When this happens, the proto-oncogenes become oncogenes, and this transition upsets the normal balance of cell cycle regulation in the cell, making uncontrolled growth possible. The chance of cancer cannot be reduced by removing proto-oncogenes from the genome, even if this were possible, as they are critical for growth, repair and homeostasis of the organism. It is only when they become mutated that the signals for growth become excessive.

One of the first oncogenes to be defined in cancer research is the ras oncogene. Mutations in the Ras family of proto-oncogenes (comprising H-Ras, N-Ras and K-Ras) are very common, being found in 20% to 30% of all human tumours. Ras was originally identified in the Harvey sarcoma virus genome, and researchers were surprised that not only was this gene present in the human genome but that, when ligated to a stimulating control element, could induce cancers in cell line cultures.

Tumor suppressor genes
Tumor suppressor genes code for anti-proliferation signals and proteins that suppress mitosis and cell growth. Generally, tumor suppressors are transcription factors that are activated by cellular stress or DNA damage. Often DNA damage will cause the presence of free-floating genetic material as well as other signs, and will trigger enzymes and pathways which lead to the activation of tumor suppressor genes. The functions of such genes is to arrest the progression of the cell cycle in order to carry out DNA repair, preventing mutations from being passed on to daughter cells. The p53 protein, one of the most important studied tumor suppressor gene, is a transcription factor activated by many cellular stressors including hypoxia and ultraviolet radiation damage.

Despite nearly half of all cancers possibly involving alterations in p53, its tumor suppressor function is poorly understood. p53 clearly has two functions: one a nuclear role as a transcription factor, and the other a cytoplasmic role in regulating the cell cycle, cell division, and apoptosis.

The Warburg effect is the preferential use of glycolysis for energy to sustain cancer growth. p53 has been shown to regulate the shift from the respiratory to the glycolytic pathway.

However, a mutation can damage the tumor suppressor gene itself, or the signal pathway which activates it, "switching it off". The invariable consequence of this is that DNA repair is hindered or inhibited: DNA damage accumulates without repair, inevitably leading to cancer.

Mutations of tumor suppressor genes that occur in germline cells are passed along to offspring, and increase the likelihood for cancer diagnoses in subsequent generations. Members of these families have increased incidence and decreased latency of multiple tumors. The tumor types are typical for each type of tumor suppressor gene mutation, with some mutations causing particular cancers, and other mutations causing others. The mode of inheritance of mutant tumor suppressors is that an affected member inherits a defective copy from one parent, and a normal copy from the other. For instance, individuals who inherit one mutant p53 allele (and are therefore heterozygous for mutated p53) can develop melanomas and pancreatic cancer, known as Li-Fraumeni syndrome. Other inherited tumor suppressor gene syndromes include Rb mutations, linked to retinoblastoma, and APC gene mutations, linked to adenopolyposis colon cancer. adenopolyposis colon cancer is associated with thousands of polyps in colon while young, leading to colon cancer at a relatively early age. Finally, inherited mutations in BRCA1 and BRCA2 lead to early onset of breast cancer.

Development of cancer was proposed in 1971 to depend on at least two mutational events. In what became known as the Knudson two-hit hypothesis, an inherited, germ-line mutation in a tumor suppressor gene would only cause cancer if another mutation event occurred later in the organism's life, inactivating the other allele of that tumor suppressor gene.

Usually, oncogenes are dominant, as they contain gain-of-function mutations, while mutated tumor suppressors are recessive, as they contain loss-of-function mutations. Each cell has two copies of the same gene, one from each parent, and under most cases gain of function mutations in just one copy of a particular proto-oncogene is enough to make that gene a true oncogene. On the other hand, loss of function mutations need to happen in both copies of a tumor suppressor gene to render that gene completely non-functional. However, cases exist in which one mutated copy of a tumor suppressor gene can render the other, wild-type copy non-functional. This phenomenon is called the dominant negative effect and is observed in many p53 mutations.

Knudson's two hit model has recently been challenged by several investigators. Inactivation of one allele of some tumor suppressor genes is sufficient to cause tumors. This phenomenon is called haploinsufficiency and has been demonstrated by a number of experimental approaches. Tumors caused by haploinsufficiency usually have a later age of onset when compared with those by a two hit process.

Cancer cell biology
Malignant progression
Often, the multiple genetic changes which result in cancer may take may years to accumulate. During this time, the biological behavior of the pre-malignant cells slowly change from the properties of normal cells to cancer-like properties. Pre-malignant tissue can have a distinctive appearance under the microscope. Among the distinguishing traits are an increased number of dividing cells, variation in nuclear size and shape, variation in cell size and shape, loss of specialized cell features, and loss of normal tissue organization. Dysplasia is an abnormal type of excessive cell proliferation characterized by loss of normal tissue arrangement and cell structure in pre-malignant cells. These early neoplastic changes must be distinguished from hyperplasia, a reversible increase in cell division caused by an external stimuli, such as a hormonal imbalance or chronic irritation.

The most severe cases of dysplasia are referred to as "carcinoma in situ." In Latin, the term "in situ" means "in place", so carcinoma in situ refers to an uncontrolled growth of cells that remains in the original location and shows no propensity to invade other tissues. Nevertheless, carcinoma in situ may develop into an invasive malignancy and is usually removed surgically, if possible.

Clonal evolution
The process of malignancy can be explained from an evolutionary perspective. Millions of years of biological evolution insure that the cellular metabolic changes that enable cancer to grow occur only very rarely. Most changes in cellular metabolism that allow cells to grow in a disorderly fashion lead to cell death. Cancer cells undergo a process analogous to natural selection, in that the few cells with new genetic changes that enhance their survival continue to multiply, and soon come to dominate the growing tumor, as cells with less favorable genetic change are outcompeted. This process is called clonal evolution. Tumors often continue to evolve in response to chemotherapy treatments, and on occasion aberrant cells may acquire resistance to particular anti-cancer pharmaceuticals.

Biological properties of cancer cells

Malignant tumor cells acquire distinct biological properties:

evading apoptosis
unlimited growth potential (immortalitization) due to overabundance of telomerase
self-sufficiency of growth factors
insensitivity to anti-growth factors
increased cell division rate
altered ability to differentiate
no ability for contact inhibition
ability to invade neighbouring tissues
ability to build metastases at distant sites
ability to promote blood vessel growth (angiogenesis)

Epidemiology
Cancer epidemiology is the study of the incidence of cancer as a way to infer possible trends and causes. The first such cause of cancer was identified by British surgeon Percivall Pott, who discovered in 1775 that cancer of the scrotum was a common disease among chimney sweeps. The work of other individual physicians led to various insights, but when physicians started working together they could make firmer conclusions.

A founding paper of this discipline was the work of 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. Her ground-breaking work on cancer epidemiology was carried on by Richard Doll and Austin Bradford Hill, who published "Lung Cancer and Other Causes of Death In Relation to Smoking. A Second Report on the Mortality of British Doctors" followed in 1956 (otherwise known as the British doctors study). Richard Doll left the London Medical Research Center (MRC), to start the Oxford unit for Cancer epidemiology in 1968. With the use of computers, the unit was the first to compile large amounts of cancer data. Modern epidemiological methods are closely linked to current concepts of disease and public health policy. Over the past 50 years, great efforts have been spent on gathering data across medical practise, hospital, provincial, state, and even country boundaries, as a way to study the interdependence of environmental and cultural factors on cancer incidence.

The biggest problem facing cancer epidemiology today is the changing concept of 'cancer incidence'. For example, a breast cancer tumor with a very slow growth rate may be found with a mammogram at 50 years, while the same tumor may have been found as a noteworthy 'lump' at 70 years, depending on the specific growth factors affecting that particular patient's case. As diagnostic tools improve, this has a direct impact on the epidemiological data.

In some Western countries, such as the USA, and the UK
Cancer: Number one killer (9 November 2000). BBC News online. Retrieved 2005-01-29. cancer is overtaking cardiovascular disease as the leading cause of death. In many Third World countries cancer incidence (insofar as this can be measured) appears much lower, most likely because of the higher death rates due to infectious disease or injury. With the increased control over malaria and tuberculosis in some Third World countries, incidence of cancer is expected to rise; this is termed the epidemiologic transition in epidemiological terminology.

Cancer epidemiology closely mirrors risk factor spread in various countries. Hepatocellular carcinoma (liver cancer) is rare in the West but is the main cancer in China and neighboring countries, most likely due to the endemic presence of hepatitis B and aflatoxin in that population. Similarly, with tobacco smoking becoming more common in various Third World countries, lung cancer incidence has increased in a parallel fashion.

Prevention
Cancer prevention is defined as active measures to decrease the incidence of cancer. This can be accomplished by avoiding carcinogens or altering their metabolism, pursuing a lifestyle or diet that modifies cancer-causing factors and/or medical intervention (chemoprevention, treatment of pre-malignant lesions).

Observational epidemiologic studies that show associations between risk factors and specific cancers generate hypotheses about potential interventions that could reduce cancer incidence or morbidity. Randomized controlled trials test whether hypotheses generated by epidemiologic trials and laboratory research actually result in reduced cancer incidence and mortality.

Examples of modifiable cancer risk factors include alcohol consumption (associated with increased risk of oral, esophageal, breast, and other cancers), smoking (although 20% of women with lung cancer have never smoked, versus 10% of men), physical inactivity (associated with increased risk of colon, breast, and possibly other cancers), and being overweight (associated with colon, breast, endometrial, and possibly other cancers). Based on epidemiologic evidence, it is now thought that avoiding excessive alcohol consumption may contribute to reductions in risk of certain cancers; however, compared with tobacco exposure, the magnitude of effect is modest or small and the strength of evidence is often weaker. Other lifestyle and environmental factors known to affect cancer risk (either beneficially or detrimentally) include certain sexually transmitted diseases, the use of exogenous hormones, exposure to ionizing radiation and ultraviolet radiation, certain occupational and chemical exposures.

See alcohol and cancer for more on that topic.

Diet
The consensus on diet and cancer is that obesity increases the risk of developing cancer. Particular dietary practices often explain differences in cancer incidence in different countries (e.g. gastric cancer is more common in Japan, while colon cancer is more common in the United States). Studies have shown that immigrants develop the risk of their new country, often within one generation, suggesting a substantial link between diet and cancer. Whether reductions obesity in a population also reduces cancer incidence is unknown.

Despite frequent reports of particular substances (including foods) having a beneficial or detrimental effect on cancer risk, few of these have an established link to cancer. These reports are often based on studies in cultured cell media or animals. Public health recommendations cannot be made on the basis of these studies until they have been validated in an observational (or occasionally a prospective interventional) trial in humans.

Proposed dietary interventions for primary cancer risk reduction generally gain support from epidemiological association studies. Examples of such studies include reports that reduced meat consumption is associated with decreased risk of colon cancer, and reports that consumption of coffee is associated with a reduced risk of liver cancer. Studies have linked consumption of grilled meat to an increased risk of stomach cancer, colon cancer, breast cancer and pancreatic cancer, an phenomenon which could be due to the presence of carcinogens such as benzopyrene in foods cooked at high temperatures.

A 2005 study showed that consumption of a plant-based diet and lifestyle changes resulted in a reduction in cancer markers in a group of men with prostate cancer who were using no conventional treatments at the time. In breast cancer patients, a low-fat diet may provide impressive protection from breast cancer recurrence, according to results reported at the 2006 San Antonio Breast Conference.

Vitamins
The concept that cancer can be prevented through vitamin supplementation stems from early observations correlating human disease with vitamin deficiency, such as pernicious anemia with vitamin B12 deficiency, and scurvy with Vitamin C deficiency. This has largely not been proven to be the case with cancer, and vitamin supplementation is largely not proving effective in preventing cancer. The cancer-fighting components of food are also proving to be more numerous and varied than previously understood, so patients are increasingly being advised to consume fresh, unprocessed fruits and vegetables for maximal health benefits. The Omnivore's Dilemma, Andrew Pollan

The Canadian Cancer Society has advised Canadians that the intake of vitamin D has shown a reduction of cancers by close to 60%,Take vitamin D to reduce cancer risk, Canadian Cancer Society advises, and one study has shown a specific benefit for this vitamin in preventing colon cancer. Vitamin D Has Role in Colon Cancer Prevention

Vitamin D and its protective effect against cancer has been contrasted with the risk of malignancy from sun exposure. Since exposure to the sun enhances natural human production of Vitamin D, some cancer researchers have argued that the potential deleterious malignant effects of sun exposure are far outweighed by the cancer-preventing effects of extra Vitamin D synthesis in sun-exposed skin. In 2002, Dr. William B. Grant claimed that 23,800 premature cancer deaths occur in the US annually due to insufficient UVB exposure (apparently via vitamin D deficiency). http://www3.interscience.wiley.com/cgi-bin/abstract/91016211/ABSTRACT?CRETRY=1&SRETRY=0

This is higher than 8,800 deaths occurred from melanoma or squamous cell carcinoma, so the overall effect of sun exposure might be beneficial. Another research group http://cat.inist.fr/?aModele=afficheN&cpsidt=17357586 Grant WB, Garland CF, Holick MF. Comparisons of estimated economic burdens due to insufficient solar ultraviolet irradiance and vitamin D and excess solar UV irradiance for the United States. Photochem Photobiol. 2005 Nov-Dec;81(6):1276-86. estimates that 50,000–63,000 individuals in the United States and 19,000 - 25,000 in the UK die prematurely from cancer annually due to insufficient vitamin D.

The case of beta-carotene provides an example of the importance of randomized clinical trials. Epidemiologists studying both diet and serum levels observed that high levels of beta-carotene, a precursor to vitamin A, were associated with a protective effect, reducing the risk of cancer. This effect was particularly strong in lung cancer. This hypothesis led to a series of large randomized clinical trials conducted in both Finland and the United States (CARET study) during the 1980s and 1990s. This study provided about 80,000 smokers or former smokers with daily supplements of beta-carotene or placebos. Contrary to expectation, these tests found no benefit of beta-carotene supplementation in reducing lung cancer incidence and mortality. In fact, the risk of lung cancer was slightly, but not significantly, increased by beta-carotene, leading to an early termination of the study.National Cancer Institute Questions and Answers About Beta Carotene Chemoprevention Trials U.S. National Institutes of Health

Results reported in JAMA in 2007 indicate that folic acid supplementation is not effective in preventing colon cancer, and folate consumers may be more likely to form colon polyps.The Journal of the American Medical Association, 2007;297:2351-2359

Chemoprevention
Daily use of tamoxifen, a selective estrogen receptor modulator (SERM), typically for 5 years, has been demonstrated to reduce the risk of developing breast cancer in high-risk women by about 50%. A recent study reported that the selective estrogen receptor modulator raloxifene has similar benefits to tamoxifen in preventing breast cancer in high-risk women, with a more favorable side effect profile.

Raloxifene is a SERM like tamoxifen; it has been shown in the STAR trial to reduce the risk of breast cancer in high-risk women equally as well as tamoxifen. In this trial, which studied almost 20,000 women, raloxifene had fewer side effects than tamoxifen, though it did permit more DCIS to form.

Finasteride, a 5-alpha-reductase inhibitor, has been shown to lower the risk of prostate cancer, though it seems to mostly prevent low-grade tumors.

The effect of COX-2 inhibitors such as rofecoxib and celecoxib upon the risk of colon polyps have been studied in familial adenomatous polyposis patients and in the general population.
In both groups, there were significant reductions in colon polyp incidence, but this came at the price of increased cardiovascular toxicity.

Genetic testing
Genetic testing for high-risk individuals is already available for certain cancer-related genetic mutations. Carriers of genetic mutations that increase risk for cancer incidence can undergo enhanced surveillance, chemoprevention, or risk-reducing surgery.
Gene Cancer types Availability

BRCA1, BRCA2 Breast,
ovarian,
pancreatic.

Commercially available for clinical specimens

MLH1,
MSH2,
MSH6, PMS1,
PMS2
Colon,
uterine,
small bowel,
stomach,
urinary tract

Vaccination
Considerable research effort is now devoted to the development of vaccines to prevent infection by oncogenic infectious agents, as well as to mount an immune response against cancer-specific epitopes) and to potential venues for gene therapy for individuals with genetic mutations or polymorphisms that put them at high risk of cancer.

A preventive human papillomavirus vaccine exists that targets certain sexually transmitted strains of human papillomavirus that are associated with the development of cervical cancer and genital warts. The only two HPV vaccines currently on the market are Gardasil and Cervarix.

Diagnosis
Most cancers are initially recognized either because signs or symptoms appear or through screening. Neither of these lead to a definitive diagnosis, which usually requires the opinion of a pathologist.

Signs and symptoms
Roughly, cancer symptoms can be divided into three groups:

Local symptoms: unusual lumps or swelling (tumor), hemorrhage (bleeding), pain
and/or ulceration. Compression of surrounding tissues may cause symptoms such as
jaundice.
Symptoms of metastasis (spreading): enlarged lymph nodes, cough
and hemoptysis, hepatomegaly (enlarged liver), bone pain, fracture of affected
bones and neurological symptoms. Although advanced cancer may cause pain, it is
often not the first symptom.
Systemic symptoms: weight loss, poor appetite and cachexia (wasting), excessive sweating (night sweats), anemia and specific paraneoplastic phenomena, i.e. specific conditions that are due to an active cancer, such as thrombosis or hormonal changes.

Every single item in the above list can be caused by a variety of conditions (a list of which is referred to as the differential diagnosis). Cancer may be a common or uncommon cause of each item.

Biopsy
A cancer may be suspected for a variety of reasons, but the definitive diagnosis of most malignancies must be confirmed by histological examination of the cancerous cells by a pathologist. Tissue can be obtained from a biopsy or surgery. Many biopsies (such as those of the skin, breast or liver) can be done in a doctor's office. Biopsies of other organs are performed under anesthesia and require surgery in an operating room.

The tissue diagnosis indicates the type of cell that is proliferating, its histological grade and other features of the tumor. Together, this information is useful to evaluate the prognosis of this patient and choose the best treatment. Cytogenetics and immunohistochemistry may provide information about future behavior of the cancer (prognosis) and best treatment.

Screening
Cancer screening is an attempt to detect unsuspected cancers in the population. Screening tests suitable for large numbers of healthy people must be relatively affordable, safe, noninvasive procedures with acceptably low rates of false positive results. If signs of cancer are detected, more definitive and invasive follow up tests are performed to confirm the diagnosis.

Screening for cancer can lead to earlier diagnosis. Early diagnosis may lead to extended life. A number of different screening tests have been developed. Breast cancer screening can be done by breast self-examination. Screening by regular mammograms detects tumors even earlier than self-examination, and many countries use it to systematically screen all middle-aged women. Colorectal cancer can be detected through fecal occult blood testing and colonoscopy, which reduces both colon cancer incidence and mortality, presumably through the detection and removal of pre-malignant polyps. Similarly, cervical cytology testing (using the Pap smear) leads to the identification and excision of precancerous lesions. Over time, such testing has been followed by a dramatic reduction of cervical cancer incidence and mortality. Testicular self-examination is recommended for men beginning at the age of 15 years to detect testicular cancer. Prostate cancer can be screened for by a digital rectal exam along with prostate specific antigen (PSA) blood testing.

Screening for cancer is controversial in cases when it is not yet known if the test actually saves lives. The controversy arises when it is not clear if the benefits of screening outweigh the risks of follow-up diagnostic tests and cancer treatments. For example: when screening for prostate cancer, the PSA test may detect small cancers that would never become life threatening, but once detected will lead to treatment. This situation, called overdiagnosis, puts men at risk for complications from unnecessary treatment such as surgery or radiation. Follow up procedures used to diagnose prostate cancer (prostate biopsy) may cause side effects, including bleeding and infection. Prostate cancer treatment may cause incontinence (inability to control urine flow) and erectile dysfunction (erections inadequate for intercourse). Similarly, for breast cancer, there have recently been criticisms that breast screening programs in some countries cause more problems than they solve. This is because screening of women in the general population will result in a large number of women with false positive results which require extensive follow-up investigations to exclude cancer, leading to having a high number-to-treat (or number-to-screen) to prevent or catch a single case of breast cancer early.

Cervical cancer screening via the Pap smear has the best cost-benefit profile of all the forms of cancer screening from a public health perspective as, being largely caused by a virus, it has clear risk factors (sexual contact), and the natural progression of cervical cancer is that it normally spreads slowly over a number of years therefore giving more time for the screening program to catch it early. Moreover, the test itself is easy to perform and relatively cheap.

For these reasons, it is important that the benefits and risks of diagnostic procedures and treatment be taken into account when considering whether to undertake cancer screening.

Use of medical imaging to search for cancer in people without clear symptoms is similarly marred with problems. There is a significant risk of detection of what has been recently called an incidentaloma - a benign lesion that may be interpreted as a malignancy and be subjected to potentially dangerous investigations.

Canine cancer detection has shown promise, but is still in the early stages of research.

Treatment
Cancer can be treated by surgery, chemotherapy, radiation therapy, immunotherapy, monoclonal antibody therapy or other methods. The choice of therapy depends upon the location and grade of the tumor and the stage of the disease, as well as the general state of the patient (performance status). A number of experimental cancer treatments are also under development.

Complete removal of the cancer without damage to the rest of the body is the goal of treatment. Sometimes this can be accomplished by surgery, but the propensity of cancers to invade adjacent tissue or to spread to distant sites by microscopic metastasis often limits its effectiveness. The effectiveness of chemotherapy is often limited by toxicity to other tissues in the body. Radiation can also cause damage to normal tissue.

Because "cancer" refers to a class of diseases, it is unlikely that there will ever be a single "cure for cancer" any more than there will be a single treatment for all infectious diseases.

Surgery
In theory, cancers can be cured if entirely removed by surgery, but this is not always possible. When the cancer has metastasized to other sites in the body prior to surgery, complete surgical excision is usually impossible. In the Halstedian model of cancer progression, tumors grow locally, then spread to the lymph nodes, then to the rest of the body. This has given rise to the popularity of local-only treatments such as surgery for small cancers. Even small localized tumors are increasingly recognized as possessing metastatic potential.

Examples of surgical procedures for cancer include mastectomy for breast cancer and prostatectomy for prostate cancer. The goal of the surgery can be either the removal of only the tumor, or the entire organ. A single cancer cell is invisible to the naked eye but can regrow into a new tumor, a process called recurrence. For this reason, the pathologist will examine the surgical specimen to determine if a margin of healthy tissue is present, thus decreasing the chance that microscopic cancer cells are left in the patient.

In addition to removal of the primary tumor, surgery is often necessary for staging, e.g. determining the extent of the disease and whether it has metastasized to regional lymph nodes. Staging is a major determinant of prognosis and of the need for adjuvant therapy.

Occasionally, surgery is necessary to control symptoms, such as spinal cord compression or bowel obstruction. This is referred to as palliative treatment.

Radiation therapy
Radiation therapy (also called radiotherapy, X-ray therapy, or irradiation) is the use of ionizing radiation to kill cancer cells and shrink tumors. Radiation therapy can be administered externally via external beam radiotherapy (EBRT) or internally via brachytherapy. The effects of radiation therapy are localised and confined to the region being treated. Radiation therapy injures or destroys cells in the area being treated (the "target tissue") by damaging their genetic material, making it impossible for these cells to continue to grow and divide. Although radiation damages both cancer cells and normal cells, most normal cells can recover from the effects of radiation and function properly. The goal of radiation therapy is to damage as many cancer cells as possible, while limiting harm to nearby healthy tissue. Hence, it is given in many fractions, allowing healthy tissue to recover between fractions.

Radiation therapy may be used to treat almost every type of solid tumor, including cancers of the brain, breast, cervix, larynx, lung, pancreas, prostate, skin, stomach, uterus, or soft tissue sarcomas. Radiation is also used to treat leukemia and lymphoma. Radiation dose to each site depends on a number of factors, including the radiosensitivity of each cancer type and whether there are tissues and organs nearby that may be damaged by radiation. Thus, as with every form of treatment, radiation therapy is not without its side effects.

Chemotherapy
Chemotherapy is the treatment of cancer with drugs ("anticancer drugs") that can destroy cancer cells. In current usage, the term "chemotherapy" usually refers to cytotoxic drugs which affect rapidly dividing cells in general, in contrast with targeted therapy (see below). Chemotherapy drugs interfere with cell division in various possible ways, e.g. with the duplication of DNA or the separation of newly formed chromosomes. Most forms of chemotherapy target all rapidly dividing cells and are not specific for cancer cells, although some degree of specificity may come from the inability of many cancer cells to repair DNA damage, while normal cells generally can. Hence, chemotherapy has the potential to harm healthy tissue, especially those tissues that have a high replacement rate (e.g. intestinal lining). These cells usually repair themselves after chemotherapy.

Because some drugs work better together than alone, two or more drugs are often given at the same time. This is called "combination chemotherapy"; most chemotherapy regimens are given in a combination.

The treatment of some leukaemias and lymphomas requires the use of high-dose chemotherapy, and total body irradiation (TBI). This treatment ablates the bone marrow, and hence the body's ability to recover and repopulate the blood. For this reason, bone marrow, or peripheral blood stem cell harvesting is carried out before the ablative part of the therapy, to enable "rescue" after the treatment has been given. This is known as autologous transplantation. Alternatively, bone marrow may be transplanted from a matched unrelated donor (MUD).

Targeted therapies
Targeted therapy, which first became available in the late 1990s, has had a significant impact in the treatment of some types of cancer, and is currently a very active research area. This constitutes the use of agents specific for the deregulated proteins of cancer cells. Small molecule targeted therapy drugs are generally inhibitors of enzymatic domains on mutated, overexpressed, or otherwise critical proteins within the cancer cell. Prominent examples are the tyrosine kinase inhibitors imatinib and gefitinib.

Monoclonal antibody therapy is another strategy in which the theraputic agent is an antibody which specifically binds to a protein on the surface of the cancer cells. Examples include the anti-HER2/neu antibody trastuzumab (Herceptin®) used in breast cancer, and the anti-CD20 antibody rituximab, used in a variety of B-cell malignancies.

Targeted therapy can also involve small peptides as "homing devices" which can bind to cell surface receptors or affected extracellular matrix surrounding the tumor. Radionuclides which are attached to this peptides (e.g. RGDs) eventually kill the cancer cell if the nuclide decays in the vicinity of the cell. Especially oligo- or multimers of these binding motifs are of great interest, since this can lead to enhanced tumor specificity and avidity.

Immunotherapy
Cancer immunotherapy refers to a diverse set of therapeutic strategies designed to induce the patient's own immune system to fight the tumor. Contemporary methods for generating an immune response against tumours include intravesical BCG immunotherapy for superficial bladder cancer, and use of interferons and other cytokines to induce an immune response in renal cell carcinoma and melanoma patients. Vaccines to generate specific immune responses are the subject of intensive research for a number of tumours, notably malignant melanoma and renal cell carcinoma. Sipuleucel-T is a vaccine-like strategy in late clinical trials for prostate cancer in which dendritic cells from the patient are loaded with prostatic acid phosphatase peptides to induce a specific immune response against prostate-derived cells.

Allogeneic hematopoietic stem cell transplantation ("bone marrow transplantation" from a genetically non-identical donor) can be considered a form of immunotherapy, since the donor's immune cells will often attack the tumor in a phenomenon known as graft-versus-tumor effect. For this reason, allogeneic HSCT leads to a higher cure rate than autologous transplantation for several cancer types, although the side effects are also more severe.

Hormonal therapy
The growth of some cancers can be inhibited by providing or blocking certain hormones. Common examples of hormone-sensitive tumors include certain types of breast and prostate cancers. Removing or blocking estrogen or testosterone is often an important additional treatment. In certain cancers, administration of hormone agonists, such as progestogens may be therapeutically beneficial.

Symptom control
Although the control of the symptoms of cancer is not typically thought of as a treatment directed at the cancer, it is an important determinant of the quality of life of cancer patients, and plays an important role in the decision whether the patient is able to undergo other treatments. Although all practicing doctors have the therapeutic skills to control pain, nausea, vomiting, diarrhea, hemorrhage and other common problems in cancer patients, the multidisciplinary specialty of palliative care has arisen specifically in response to the symptom control needs of this group of patients.

Pain medication, such as morphine and oxycodone, and antiemetics, drugs to suppress nausea and vomiting, are very commonly used in patients with cancer-related symptoms.

Chronic pain due to cancer is almost always associated with continuing tissue damage due to the disease process or the treatment (i.e. surgery, radiation, chemotherapy). Although there is always a role for environmental factors and affective disturbances in the genesis of pain behaviors, these are not usually the predominant etiologic factors in patients with cancer pain. Furthermore, many patients with severe pain associated with cancer are nearing the end of their lives and palliative therapies are required. Issues such as social stigma of using opioids, work and functional status, and health care consumption are not likely to be important in the overall case management. Hence, the typical strategy for cancer pain management is to get the patient as comfortable as possible using opioids and other medications, surgery, and physical measures.

Complementary and alternative
Complementary and alternative medicine (CAM) treatments are the diverse group of medical and health care systems, practices, and products that are not part of conventional medicine. Oncology, the study of human cancer, has a long history of incorporating unconventional or botanical treatments into mainstream cancer therapy. Some examples of this phenomenon include the chemotherapy agent paclitaxel, which is derived from the bark of the Pacific Yew tree, and ATRA, all-trans retinoic acid, a derivative of Vitamin A that induces cures in an aggressive leukemia known as acute promyelocytic leukemia. Many "complementary" and "alternative" medicines for cancer have not been studied using the scientific method, such as in well-designed clinical trials, or they have only been studied in preclinical (animal or in-vitro) laboratory studies. Many times, "complementary" and "alternative" medicines are supported by marketing materials and "testimonials" from users of the substances. Frequently, when these treatments are subjected to rigorous scientific testing, they are found not to work. A recent example was reported at the 2007 annual meeting of the American Society of Clinial Oncology: a Phase III clinical trial comparing shark cartilage extract to placebo in non-small cell lung cancer demonstrated no benefit of the shark cartilage extract, AE-491.

"Complementary medicine" refers to methods and substances used along with conventional medicine, while "alternative medicine" refers to compounds used instead of conventional medicine. A study of CAM use in patients with cancer in the July 2000 issue of the Journal of Clinical Oncology found that 69 percent of 453 cancer patients had used at least one CAM therapy as part of their cancer treatment.

Some complementary measures include botanical medicine, such as an NIH trial currently underway testing mistletoe extract combined with chemotherapy for the treatment of solid tumors, acupuncture for managing chemotherapy-associated nausea and vomiting and in controlling pain associated with surgery, psychological approaches such as "imaging" or meditation to aid in pain relief or improve mood.

A wide range of alternative treatments have been offered for cancer over the last century. The appeal of alternative cures arises from the daunting risks, costs, or potential side effects of many conventional treatments, or in the limited prospect for cure. No alternative therapies have been shown in any scientific study to effectively treat cancer.

Treatment trials
Clinical trials, also called research studies, test new treatments in people with cancer. The goal of this research is to find better ways to treat cancer and help cancer patients. Clinical trials test many types of treatment such as new drugs, new approaches to surgery or radiation therapy, new combinations of treatments, or new methods such as gene therapy.

A clinical trial is one of the final stages of a long and careful cancer research process. The search for new treatments begins in the laboratory, where scientists first develop and test new ideas. If an approach seems promising, the next step may be testing a treatment in animals to see how it affects cancer in a living being and whether it has harmful effects. Of course, treatments that work well in the lab or in animals do not always work well in people. Studies are done with cancer patients to find out whether promising treatments are safe and effective.

Patients who take part may be helped personally by the treatment(s) they receive. They get up-to-date care from cancer experts, and they receive either a new treatment being tested or the best available standard treatment for their cancer. Of course, there is no guarantee that a new treatment being tested or a standard treatment will produce good results. New treatments also may have unknown risks, but if a new treatment proves effective or more effective than standard treatment, study patients who receive it may be among the first to benefit.

Prognosis
Cancer has a reputation for being a deadly disease. While this certainly applies to certain particular types, the truths behind the historical connotations of cancer are increasingly being overturned by advances in medical care. Some types of cancer have a prognosis that is substantially better than nonmalignant diseases such as heart failure and stroke.

Progressive and disseminated malignant disease has a substantial impact on a cancer patient's quality of life, and many cancer treatments (such as chemotherapy) may have severe side-effects. In the advanced stages of cancer, many patients need extensive care, affecting family members and friends. Palliative care solutions may include permanent or "respite" hospice nursing.

Cancer patients, for the first time in the history of oncology, are visibly returning to the athletic arena and workplace. Patients are living longer with either quiescent persistent disease or even complete, durable remissions. The stories of Lance Armstrong, who won the Tour de France after treatment for metastatic testicular cancer, or Tony Snow, who was working as the White House Press Secretary as of June, 2007 despite relapsed colon cancer, continue to be an inspiration to cancer patients everywhere.

Emotional impact
Many local organizations offer a variety of practical and support services to people with cancer. Support can take the form of support groups, counseling, advice, financial assistance, transportation to and from treatment, films or information about cancer. Neighborhood organizations, local health care providers, or area hospitals may have resources or services available.

While some people are reluctant to seek counseling, studies show that having someone to talk to reduces stress and helps people both mentally and physically. Counseling can also provide emotional support to cancer patients and help them better understand their illness. Different types of counseling include individual, group, family, self-help (sometimes called peer counseling), bereavement, patient-to-patient, and sexuality.

Many governmental and charitable organizations have been established to help patients cope with cancer. These organizations often are involved in cancer prevention, cancer treatment, and cancer research. Examples include: American Cancer Society, National Comprehensive Cancer Network, Lance Armstrong Foundation, BC Cancer Agency, Macmillan Cancer Relief, the Terry Fox Foundation, Cancer Research UK, Cancer Research Foundation, Canadian Cancer Society, International Agency for Research on Cancer, The Cancer Council Australia and the National Cancer Institute (US).

History
Today, the Greek term carcinoma is the medical term for a malignant tumor derived from epithelial cells. It is Celsus who translated carcinos into the Latin cancer, also meaning crab.
Galen used "oncos" to describe all tumours, the root for the modern word oncology.Ralph W. Moss, Ph.D Galen on Cancer - How Ancient Physicians Viewed Malignant Disease 1989 Speech

Hippocrates described several kinds of cancers. He called benign tumours oncos, Greek for swelling, and malignant tumours carcinos, Greek for crab or crayfish. This name probably comes from the appearance of the cut surface of a solid malignant tumour, with a roundish hard center surrounded by pointy projections, vaguely resembling the shape of a crab (see photo). He later added the suffix -oma, Greek for swelling, giving the name carcinoma. Since it was against Greek tradition to open the body, Hippocrates only described and made drawings of outwardly visible tumors on the skin, nose, and breasts. Treatment was based on the humor theory of four bodily fluids (black and yellow bile, blood, and phlegm). According to the patient's humor, treatment consisted of diet, blood-letting, and/or laxatives. Through the centuries it was discovered that cancer could occur anywhere in the body, but humor-theory based treatment remained popular until the 19th century with the discovery of cells.

Though treatment remained the same, in the 16th and 17th centuries it became more acceptable for doctors to dissect bodies to discover the cause of death. The German professor Wilhelm Fabry believed that breast cancer was caused by a milk clot in a mammary duct. The Dutch professor Francois de la Boe Sylvius, a follower of Descartes, believed that all disease was the outcome of chemical processes, and that acidic lymph fluid was the cause of cancer. His contemporary Nicolaes Tulp believed that cancer was a poison that slowly spreads, and concluded that it was contagious.
Marilyn Yalom "A history of the breast" 1997 Publisher: New York : Alfred A. Knopf
ISBN 0-679-43459-3

With the widespread use of the microscope in the 18th century, it was discovered that the 'cancer poison' spread from the primary tumor through the lymph nodes to other sites ("metastasis"). This view of the disease was first formulated by the English surgeon Campbell De Morgan between 1871 and 1874 . The use of surgery to treat cancer had poor results due to problems with hygiene. The renowned Scottish surgeon Alexander Monro saw only 2 breast tumor patients out of 60 surviving surgery for two years. In the 19th century, asepsis improved surgical hygiene and as the survival statistics went up, surgical removal of the tumor became the primary treatment for cancer. With the exception of William Coley who in the late 1800s felt that the rate of cure after surgery had been higher before asepsis (and who injected bacteria into tumors with mixed results), cancer treatment became dependent on the individual art of the surgeon at removing a tumor. During the same period, the idea that the body was made up of various tissues, that in turn were made up of millions of cells, laid rest the humor-theories about chemical imbalances in the body. The age of cellular pathology was born.

When Marie Curie and Pierre Curie discovered radiation at the end of the 19th century, they stumbled upon the first effective non-surgical cancer treatment. With radiation came also the first signs of multi-disciplinary approaches to cancer treatment. The surgeon was no longer operating in isolation, but worked together with hospital radiologists to help patients. The complications in communication this brought, along with the necessity of the patient's treatment in a hospital facility rather than at home, also created a parallel process of compiling patient data into hospital files, which in turn led to the first statistical patient studies.

Cancer patient treatment and studies were restricted to individual physicians' practices until World War II, when medical research centers discovered that there were large international differences in disease incidence. This insight drove national public health bodies to make it possible to compile health data across practises and hospitals, a process that many countries do today. The Japanese medical community observed that the bone marrow of bomb victims in Hiroshima and Nagasaki was completely destroyed. They concluded that diseased bone marrow could also be destroyed with radiation, and this led to the discovery of bone marrow transplants for leukemia. Since WWII, trends in cancer treatment are to improve on a micro-level the existing treatment methods, standardize them, and globalize them as a way to find cures through epidemiology and international partnerships.

Research
Cancer research is the intense scientific effort to understand disease processes and discover possible therapies. The improved understanding of molecular biology and cellular biology due to cancer research has led to a number of new, effective treatments for cancer since President Nixon declared "War on Cancer" in 1971.

See also

* American Cancer Society
* National Comprehensive Cancer Network
* Alcohol and cancer
* Diet and cancer
* Oncology
* List of oncology-related terms
* American Association for Cancer Research
* European Organisation for Research and Treatment of Cancer (EORTC)

References

* The Basic Science of Oncology. Tannock IF, Hill RP et al (eds) 4th ed.2005 McGraw-Hill.
* Principles of Cancer Biology. Kleinsmith, LJ (2006). Pearson Benjamin Cummings.

* Full text

Professional and research
* American Cancer Society Homepage
* American Cancer Society resources on clinical trials What to look for in clinical trials and how to find open trials.
* / The Leukemia and Lymphoma Society
* American Cancer Society Treatment Decision Tools – Trusted tools for helping patients make informed decisions
* American Association for Cancer Research A non-profit organization supporting advances in the knowledge of causes, diagnosis, treatment and prevention of cancer.
* The World Health Organisation's cancer site A review of worldwide strategies for the prevention and treatment of cancer.
* World Health Organization's fact sheet on cancer
* National Cancer Institute US Government agency responsible for conducting and supporting research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer, rehabilitation from cancer, and the continuing care of cancer patients and the families of cancer patients.
* National Comprehensive Cancer Network - Free guidelines for professionals and many pages of quality information for patients with all types of cancers
* The Institute of Cancer Research One of the world?s foremost independent cancer research organisations, based in the United Kingdom.
* EORTC European Organization for Research and Treatment of Cancer. A European non-profit organization that sets up and executes clinical trials.
* International Society for Biological Therapy of Cancer Society of medical professionals committed to investigating, developing and utilizing biologicals and biological therapy for the treatment of malignant disease.
* National Cancer Institute of Canada Longest-standing Canadian research organization devoted to advancing cancer control.
* Cancer Facts & Figures 2005 - 2005 United States Cancer Statistics
*
* Canadian Cancer Statistics 2006 - This publication reports cancer incidence and mortality in Canada, analyzed by gender, age and province/territory.
* Cancer Medicine, 6th Edition Textbook
*
* Diet, Nutrition and the prevention of chronic diseases (including cancer) by a Joint WHO/FAO Expert consultation (2003). Summary by GreenFacts.
* Virtual Cancer Centre - information resource with the latest cancerous diseases news by professionals of Oncology, Haematology, Radiation Oncology and Palliative Care.

Support and advocacy
*National Comprehensive Cancer Network Listing of Clinical Practice Guidelines in Oncology - Standards of Care written by leading cancer centers in the U.S.A.
*American Cancer Society Patient advocate group
* Action Cancer Northern Ireland Cancer Charity providing screening and support
* Canadian Cancer Society Information on all types of cancer, ways to reduce your risk. Support for people living with cancer. Advocating for healthy public policy.
* American Association for Cancer Research Survivor and Patient Advocacy
* Cancer from MedlinePlus - provides links to news, general sites, diagnosis, treatment and alternative therapies, clinical trials, research, related issues, organizations, other MedlinePlus Cancers Topics and Living with Cancer, and more. Also, links to pre-formulated searches of the MEDLINE/PubMed database for recent research articles.
* Cancer Research UK - Cancer Resources - In-depth, up-to-date information for people with a professional or general interest in cancer and health.
* Cancer Council of Australia - Australia's national non-government cancer control organisation, involved in research, information, prevention, patient treatment and support.
* Sydney Children's Hospital: Centre for Cancer and Blood Disorders - Offers information on childhood cancer, treatment options, and support. [Australia].
* ACOR - Association of Cancer Online Resources ACOR is a unique collection of online communities designed to provide timely and accurate information in a supportive environment. ACOR offers access to mailing lists that provide support, information, and community to everyone affected by cancer and related disorders.
* Inside Cancer Multimedia guide to cancer biology from Cold Spring Harbor Laboratory

To view information on another Digestive Disease, click on Digestive Diseases Library!

Digestive Disease Library

Liver Cancer

2007-09-05T18:20:00.000-07:00

Liver cancer
From Wikipedia, the free encyclopediaJump to: navigation, search

Classification and external resources

MeSH D008113

Liver cancer or hepatic cancer is properly considered to be a cancer which starts in the liver, as opposed to a cancer which originates in another organ and migrates to the liver, known as a liver metastasis. For a thorough understanding of liver cancer it is important to have an understanding of how the liver functions. The liver is one of the largest organs in the body. It is located below the right lung and under the ribcage. The liver is divided into two lobes: the right lobe and the left lobe. Protein is obtained by the liver from the portal vein, which carries nutrient-rich blood from the intestines to the liver. The hepatic artery supplies the liver with blood that is rich in oxygen. Liver cancer thus consists of the presence of malignant hepatic tumors, growths on or in the liver (medical terms pertaining to the liver often start in hepato, or hepatic from the Greek word for liver, hēpar, stem hēpat-). Liver tumors may be discovered on medical imaging, which may occur incidentally to imaging performed for a different disease than the cancer itself, or may present symptomatically, as an abdominal mass, abdominal pain, jaundice, nausea or some other liver dysfunction.[1]

Classification
There are many forms of liver cancer, although many cancers found in the liver are metastases from other tumors, frequently of the GI tract (like colon cancer, carcinoid tumors mainly of the appendix, etc.), but also from breast cancer, ovarian cancer, lung cancer, renal cancer, prostate cancer, etc.

The most frequent, liver cancer is hepatocellular carcinoma (HCC) (also named hepatoma, which is a misnomer because adenomas are usually benign). Patients who develop this cancer normally are in the younger population. This tumor also has a variant type that consists of both HCC and cholangiocarcinoma components. The cells of the bile duct coexist next to the bile ducts that drain the bile produced by the hepatocytes of the liver. The cancers arose from the blood vessel cells in the liver are known has hemangioendotheliomas.

As well as mixed tumors, rarer forms of liver cancer include:

mesenchymal tissue
Sarcoma
Hepatoblastoma, a rare malignant tumor, primarily developing in children. Most of these tumors form in the right lobe.
Cholangiocarcinoma (bile duct cancers), which account for 1 or 2 out of every 10 cases of liver cancer. These cancers start in the small tubes (called bile ducts) that carry bile to the intestine.
Angiosarcoma and hemangiosarcoma: These are rare forms of cancer that start in the blood vessels of the liver. These tumors grow quickly. Often by the time they are found they are too widespread to be removed. Most patients do not live more than a year after diagnosis.
Lymphoma of liver: A rare form of lymphoma that usually have diffuse infiltration to liver. It may also form a liver mass in rare occasions.

Symptoms of Liver cancer

Symptoms of Cholangiocarcinoma
Jaundice
Abdominal pain
Weight loss
Hepatomegaly[2]
Symptoms of hepatocellular carcinoma
Abdominal mass
Abdominal pain
Emesis
Anemia
Back pain
Jaundice
Itching
Weight loss
Fever[3]

Causes

A 2009 study suggested that l-carnitine deficiency is a risk factor for liver cancer, and that supplementation with it could reduce the risk.[4]

Japan being member of International Cancer Genome Consortium is leading efforts to map liver cancer's complete genome.

Management

A PET-CT scan may be suggested if doctors are considering surgery as a treatment. It gives more detailed information about the part of the body being scanned.[5] The correct treatment of liver cancer can mean the difference between life and death. Not all patients with cancers in the liver are potentially curable. These are some of the treatments available: Surgery, Chemotherapy, Immunotherapy, Photodynamic Therapy, Hyperthermia, Radiation Therapy and Radiosurgery.[6]
Treatment of hepatocellular carcinoma
Partial hepatectomy to resect all of the tumor.
Liver transplantation
Cyroablation
Chemoembolization
Radiotherapy
Sorafenib
Radiofrequency ablation[7]
[edit] Treatment of Cholangiocarcinoma
Photodynamic therapy
Brachytherapy
Radiotherapy
Liver transplantation[8]
[edit] Treatment of hepatoblastoma
Chemotherapy, including vincristine, cyclophosphamide, and doxorubicin
Radiotherapy
Liver transplantation
Surgical resection[9]

Epidemeology
Age-standardized death from liver cancer per 100,000 inhabitants in 2004.[10]
no data

less than 7.5

7.5-15

15-22.5

22.5-30

30-37.5

37.5-45

45-52.5

52.5-60

60-67.5

67.5-75

75-110

more than 110 Liver cancer as a cause of death is reported at less than 30 cases per 100,000 inhabitants in most of the world, with higher rates observed in parts of Africa and eastern Asia.

References
1.^ http://www.liverfoundation.org/education/info/progression/
2.^ 3.^ http://www.childrenshospital.org/az/Site1015/mainpageS1015P0.html
4.^ Long-term L-carnitine supplementation prevents development of liver cancer.
5.^http://www.cancerbackup.org.uk/Cancertype/Liversecondary/Causesdiagnosis/Furthertests

6.^Radiosurgery treatment for liver cancer

7.^ http://www.mayoclinic.com/health/liver-cancer/DS00399/DSECTION=treatments-and-drugs
8.^ http://emedicine.medscape.com/article/277393-treatment
9.^ http://emedicine.medscape.com/article/986802-treatment
10.^ "WHO Disease and injury country estimates". World Health Organization. 2009. http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html. Retrieved Nov. 11, 2009.
External links
The Liver Cancer Web Page at Johns Hopkins University
Liver cancer at Mayo Clinic
Blue Faery: The Adrienne Wilson Liver Cancer Association

Lung Cancer

2007-09-05T18:19:00.000-07:00

Lung cancer
From Wikipedia, the free encyclopedia

Lung cancer
Classification & external resources

ICD-10
C 33.-C 34.
ICD-9
162
DiseasesDB
7616
MedlinePlus
007194
eMedicine
med/1333 med/1336 emerg/335 radio/807 radio/405 radio/406
MeSH
D002283

Cross section of a human lung. The white
area in the upper lobe is cancer; the
black areas indicate the patient was a
smoker.

Lung cancer is a disease where tissue in the lung grows out of control. This leads to invasion of adjacent tissue and infiltration beyond the lungs (metastasis). Lung cancer, the most common cause of cancer-related death in men and the second most common in women,[1][2] is responsible for 1.3 million deaths worldwide annually.[3] The most common symptoms are shortness of breath, cough (including coughing up blood), and weight loss.[4]

The main types of lung cancer are small cell lung cancer and non-small cell lung cancer. This distinction is important because non-small cell lung cancer is sometimes treated with surgery, while small cell cancer is not. Also, small cell lung cancer usually responds better to chemotherapy.[5]

The most significant risk factor for developing lung cancer is long-term exposure to inhaled carcinogens, especially tobacco smoke.[6] The occurrence of lung cancer in non-smokers, who account for less than 10% of cases, appears to be due to a combination of genetic factors.[7][8] Radon gas,[9] asbestos,[10] and air pollution[11][12][13] may also contribute to the development of lung cancer.

Lung cancer may be seen on chest x-ray and CT scan. The diagnosis is confirmed with a biopsy. This is usually performed via bronchoscopy or CT-guided biopsy.
Treatment and prognosis depend upon the histological type of cancer, the stage (degree of spread), and the patient's performance status. Possible treatments include surgery, chemotherapy, and radiotherapy. Even with treatment, the overall five-year survival rate is 14%.[4]

Classification
Types
There are two main types of lung cancer categorized by the size and appearance of the malignant cells seen by a histopathologist under a microscope: non-small cell (80%) and small-cell (roughly 20%) lung cancer.[4] This classification, although based on simple histological criteria, has very important implications for clinical management and prognosis of the disease.

Non-small cell lung cancer (NSCLC)
The non-small cell lung cancers are grouped together because their prognosis and management are roughly identical. There are three main sub-types: squamous cell lung carcinoma, adenocarcinoma and large cell lung carcinoma. When NSCLC cannot be subtyped, it is assigned SNOMED code 8046/3.

Squamous cell lung carcinoma, accounting for 29% of lung cancers,[4] usually starts near a central bronchus. Cavitation and necrosis within the center of the cancer is a common finding. Well-differentiated squamous cell lung cancers often grow more slowly than other cancer types.[5]

Adenocarcinoma is the most common subtype of NSCLC, accounting for 32% of lung cancers.[4] It usually originates in peripheral lung tissue. Most cases of adenocarcinoma are associated with smoking. However, among people who have never smoked ("never-smokers"), adenocarcinoma is the most common form of lung cancer.[14] A subtype of adenocarcinoma, the bronchioloalveolar carcinoma, is more common in female never-smokers, and may have different responses to treatment.[15]

Large cell lung carcinoma is a fast-growing form, accounting for 9% of lung cancers,[4] that grows near the surface of the lung.[16] It is often poorly differentiated and tends to metastasize early.[5]

Small cell lung cancer (SCLC)

Small cell lung carcinoma (microscopic view of a
core needle biopsy)

Small cell lung cancer (SCLC, also called "oat cell carcinoma") is the less common form of lung cancer. It tends to start in the larger breathing tubes and grows rapidly becoming quite large. The oncogene most commonly involved is L-myc. The "oat" cell contains dense neurosecretory granules which give this an endocrine/paraneoplastic syndrome association. It is initially more sensitive to chemotherapy, but ultimately carries a worse prognosis and is often metastatic at presentation. This type of lung cancer is strongly associated with smoking.

Other types
Rarer forms of lung cancer include carcinoid,[17] adenoid cystic carcinoma (cylindroma)[18] and mucoepidermoid carcinoma.[19]

Metastatic cancers
The lung is a common place for metastasis from tumors in other parts of the body. These cancers, however, are identified by the site of origin, e.g. a breast cancer metastasis to the lung is still known as breast cancer. The adrenal glands, liver, brain, and bone are the most common sites of metastasis from primary lung cancer itself.

Staging
See also: Non-small cell lung cancer staging
Lung cancer staging is an assessment of the degree of spread of the cancer from its original source. It is an important factor affecting the prognosis and potential treatment of lung cancer.
Non-small cell lung cancer is staged from IA ("one A", best prognosis) to IV ("four", worst prognosis).[20] Small cell lung cancer is classified as limited stage if it is confined to one half of the chest and within the scope of a single radiotherapy field. Otherwise it is extensive stage.[21]

Signs and symptoms
Symptoms that suggest lung cancer include:[4]

dyspnea (shortness of breath)
hemoptysis (coughing up blood)
chronic coughing or change in regular coughing pattern
wheezing
chest pain or pain in the abdomen
cachexia (weight loss), fatigue and loss of appetite
dysphonia (hoarse voice)
clubbing of the fingernails (uncommon)
difficulty swallowing

If the cancer grows in the airway, it may obstruct airflow, causing breathing difficulties. This can lead to accumulation of secretions behind the blockage, predisposing the patient to pneumonia.
Many lung cancers have a rich blood supply. The surface of the cancer may be fragile, leading to bleeding from the cancer into the airway. This blood may subsequently be coughed up.
Depending on the type of tumor, so-called paraneoplastic phenomena may initially attract attention to the disease. In lung cancer, these phenomena may include Lambert-Eaton myasthenic syndrome (muscle weakness due to auto-antibodies), hypercalcemia or SIADH. Tumors in the top (apex) of the lung, known as Pancoast tumors, may invade the local part of the sympathetic nervous system, leading to changed sweating patterns and eye muscle problems (a combination known as Horner's syndrome), as well as muscle weakness in the hands due to invasion of the brachial plexus.

Many of the symptoms of lung cancer (bone pain, fever, weight loss ) are nonspecific; in the elderly, these may be attributed to comorbid illness.[5] In many patients, the cancer has already spread beyond the original site by the time they have symptoms and seek medical attention. Common sites of metastasis include the bone, such as the spine (causing back pain and occasionally spinal cord compression), the liver and the brain. About 10% of people with lung cancer do not have symptoms of it at the time of diagnosis; these cancers are usually found on routine chest x-rays.[4]

Causes
The main causes of lung cancer (and cancer in general) include carcinogens (such as those in tobacco smoke), ionizing radiation, and viral infection. This exposure causes cumulative changes to the DNA in the tissue lining the bronchi of the lungs (the bronchial epithelium). As more tissue becomes damaged, eventually a cancer develops.

Smoking
The incidence of lung cancer is highly correlated with smoking. Source:NIH.
Smoking, particularly of cigarettes, is by far the main contributor to lung cancer. In the United States, smoking is estimated to account for 87% of lung cancer cases (90% in men and 85% in women).[6] Among male smokers, the lifetime risk of developing lung cancer is 17.2%. Among female smokers, the risk is 11.6%. This risk is significantly lower in non-smokers: 1.3% in men and 1.4% in women.[22] Cigarette smoke contains over 60 known carcinogens[23] including radioisotopes from the radon decay sequence, nitrosamine, and benzopyrene. Additionally, nicotine appears to depress the immune response to malignant growths in exposed tissue. The length of time a person continues to smoke as well as the amount smoked increases the person's chance of developing lung cancer. If a person stops smoking, this chance steadily decreases as damage to the lungs is repaired and contaminant particles are gradually removed. Across the developed world, almost 90% of lung cancer deaths are caused by smoking.[24] In addition, there is evidence that lung cancer in never-smokers has a better prognosis than in smokers,[25] and that patients who smoke at the time of diagnosis have shorter survival than those who have quit.[26]

Passive smoking—the inhalation of smoke from another's smoking— is a cause of lung cancer in non-smokers. Studies from the U.S. (1986,[27][28] 1992, [29] 1997,[30] 2001, [31] 2003[32]), Europe (1998[33]), the UK (1998[34][35]), and Australia (1994[36]) have consistently shown a significant increase in relative risk among those exposed to passive smoke. Recent investigation of sidestream smoke suggests it is more dangerous than direct smoke inhalation.[37]

Percentage of lung cancer deaths attributable to smoking in the developed world
35–69 years
70 years+
All ages
Men
93.9%
90.3%
92.5%
Women
68.8%
68.9%
68.8%
Both
88.7%
84.3%
86.6%

The Philip Morris tobacco company attempted to delay the release of the 1997 IARC study, to affect the wording of its conclusions, to neutralise its negative results for their business, and to counteract its impact on public and policymakers' opinion.[38][39]

Radon gas
Radon is a colorless and odourless gas generated by the breakdown of radioactive radium, which in turn is the decay product of uranium, found in the earth's crust. The radiation decay products ionize genetic material, causing mutations that sometimes turn cancerous. Radon exposure is the second major cause of lung cancer after smoking.[9]
Radon gas levels vary by locality and the composition of the underlying soil and rocks. For example, in areas such as Cornwall in the UK (which has granite as substrata), radon gas is a major problem, and buildings have to be force-ventilated with fans to lower radon gas concentrations. The United States Environmental Protection Agency (EPA) estimates that one in 15 homes in the U.S. has radon levels above the recommended guideline of 4 picoCuries per liter (pCi/L).[40] Iowa has the highest average radon concentration in the United States; studies performed there have demonstrated a 50% increased lung cancer risk with prolonged radon exposure above the EPA's action level of 4 pCi/L.[41][42]

Asbestos
Asbestos can cause a variety of lung diseases, including lung cancer. There is a synergistic effect between tobacco smoking and asbestos in the formation of lung cancer.[10] Asbestos can also cause cancer of the pleura, called mesothelioma (which is different from lung cancer).

Viruses
Viruses are known to cause lung cancer in animals[43][44] and recent evidence suggests similar potential in humans. Implicated viruses include human papillomavirus,[45] JC virus,[46] simian virus 40 (SV40), BK virus and cytomegalovirus.[47]

Pathophysiology
Main article: Carcinogenesis
Similar to many other cancers, lung cancer is initiated by activation of oncogenes or inactivation of tumor suppressor genes.[48] Oncogenes are genes that are believed make people more susceptible to cancer. Proto-oncogenes are believed to turn into oncogenes when exposed to particular carcinogens.[49] Mutations in the K-ras proto-oncogene are responsible for 20–30% of non-small cell lung cancers.[50] Chromosomal damage can lead to loss of heterozygosity. This can cause inactivation of tumor suppressor genes. Damage to chromosomes 3p, 5q, 13q and 17p are particularly common in small cell lung carcinoma. The TP53 tumor suppressor gene, located on chromosome 17p, is often affected.[51]

Several genetic polymorphisms are associated with lung cancer. These include polymorphisms in interleukin-1,[52] cytochrome P450[53] and DNA repair molecules such as XRCC1.[54] People with these polymorphisms are more likely to develop lung cancer after exposure to carcinogens.

Diagnosis

Chest x-ray showing lung cancer in
the left lung.

Performing a chest x-ray is the first step if a patient reports symptoms that may be suggestive of lung cancer. This may reveal an obvious mass, widening of the mediastinum (suggestive of spread to lymph nodes there), atelectasis (collapse), consolidation (infection) and pleural effusion. If there are no X-ray findings but the suspicion is high (e.g. a heavy smoker with blood-stained sputum), bronchoscopy and/or a CT scan may provide the necessary information. In any case, bronchoscopy or CT-guided biopsy is often necessary to identify the tumor type.[4]

CT scan showing lung cancer in the left lung.
The differential diagnosis for patients who present with abnormalities on chest x-ray includes lung cancer, as well as other nonmalignant diseases. These include infectious causes such as tuberculosis or pneumonia, or inflammatory conditions such as sarcoidosis. These diseases can result in mediastinal lymphadenopathy or lung nodules, and sometimes mimic lung cancers.[5]

Prevention

Primary prevention
See also: Smoking ban and List of smoking bans
Prevention is the most cost-effective means of fighting lung cancer on the national and global scales. While in most countries industrial and domestic carcinogens have been identified and banned, tobacco smoking is still widespread. Eliminating tobacco smoking is a primary goal in the prevention of lung cancer, and smoking cessation is an important preventative tool in this process.[55]

Policy interventions to decrease passive smoking (e.g. in restaurants and workplaces) have become more common in various Western countries, with California taking a lead in banning smoking in public establishments in 1998, Ireland playing a similar role in Europe in 2004, followed by Italy and Norway in 2005 and Scotland as well as several others in 2006, and England in 2007. New Zealand has also recently banned smoking in public places.
Only the Asian state of Bhutan has a complete smoking ban (since 2005). In many countries pressure groups are campaigning for similar bans. Arguments cited against such bans are criminalisation of smoking, increased risk of smuggling and the risk that such a ban cannot be enforced.

Screening
Main article: Lung cancer screening
Screening refers to the use of medical tests to detect disease in asymptomatic people. Possible screening tests for lung cancer include chest x-ray or computed tomography (CT) of the chest. So far, screening programs for lung cancer have not demonstrated any clear benefit. Randomized controlled trials are underway in this area to see if decreased long-term mortality can be directly observed from CT screening.[56]

Treatment
Treatment for lung cancer depends on the cancer's specific cell type, how far it has spread, and the patient's performance status. Common treatments include surgery, chemotherapy, and radiation therapy.[4]

Surgery
Main article: Lung cancer surgery
If investigations confirm lung cancer, CT scan and often positron emission tomography (PET) are used to determine whether the disease is localised and amenable to surgery or whether it has spread to the point where it cannot be cured surgically.

Blood tests and spirometry (lung function testing) are also necessary to assess whether the patient is well enough to be operated on. If spirometry reveals a very poor respiratory reserve, as may occur in chronic smokers, surgery may be contraindicated.

Surgery itself has an overall operative death rate of about 4.4%, depending on the patient's lung function and other risk factors.[57] Surgery is usually only an option in non-small cell lung cancer limited to one lung, up to stage IIIA. This is assessed with medical imaging (computed tomography, positron emission tomography). A sufficient pre-operative respiratory reserve must be present to allow adequate lung function after the tissue is removed.
Procedures include wedge excision (removal of part of a lobe), lobectomy (one lobe), bilobectomy (two lobes) or pneumonectomy (whole lung). In patients with adequate respiratory reserve, lobectomy is the preferred option, as this minimizes the chance of local recurrence. If the patient does not have enough functional lung for this, wedge excision may be performed.[58] Radioactive iodine brachytherapy at the margins of wedge excision may reduce recurrence to that of lobectomy.[59]

Chemotherapy
Small cell lung cancer is treated primarily with chemotherapy, as surgery has no demonstrable influence on survival. Primary chemotherapy is also given in metastatic non-small cell lung cancer.

The combination regimen depends on the tumor type. Non-small cell lung cancer is often treated with cisplatin or carboplatin, in combination with gemcitabine, paclitaxel, docetaxel, etoposide or vinorelbine.[60] In small cell lung cancer, cisplatin and etoposide are most commonly used.[61] Combinations with carboplatin, gemcitabine, paclitaxel, vinorelbine, topotecan and irinotecan are also used.[62][63]

Adjuvant chemotherapy for non-small cell lung cancer
Adjuvant chemotherapy refers to the use of chemotherapy after surgery to improve the outcome. During surgery, samples are taken from the lymph nodes. If these samples contain cancer, then the patient has stage II or III disease. In this situation, adjuvant chemotherapy may improve survival by up to 15%.[64][65] Standard practice is to offer platinum-based chemotherapy (e.g. cisplatin and vinorelbine).[66]

Adjuvant chemotherapy for patients with stage IB cancer is controversial as clinical trials have not clearly demonstrated a survival benefit.[67][68] Trials of preoperative chemotherapy (neoadjuvant chemotherapy) in resectable non-small cell lung cancer have been inconclusive.[69]

Radiotherapy
Radiotherapy is often given together with chemotherapy, and may be used with curative intent in patients with non-small cell lung cancer who are not eligible for surgery. For small cell lung cancer cases that are potentially curable, in addition to chemotherapy, chest radiation is often recommended.[70] The use of adjuvant thoracic radiotherapy following curative intent surgery for non-small cell lung cancer is not well established and controversial. Benefits, if any, may only be limited to those in whom the tumor has spread to the mediastinal lymph nodes. [71][72]
For both non-small cell lung cancer and small cell lung cancer patients, smaller doses of radiation to the chest may be used for symptom control (palliative radiotherapy). Unlike other treatments, it is possible to deliver palliative radiotherapy without confirming the histological diagnosis of lung cancer.

Patients with limited stage small cell lung carcinoma are usually given prophylactic cranial irradiation (PCI). This is a type of radiotherapy to the brain, used to reduce the risk of metastasis.[73] More recently, PCI has also been shown to be beneficial in those with extensive small cell lung cancer. In patients whose cancer has improved following a course of chemotherapy, PCI has been shown to reduce the cumulative risk of brain metastases within one year from 40.4% to 14.6%.[74]

Interventional radiology
Radiofrequency ablation is more frequently used for this condition as it is nontoxic and causes very little pain. It is especially effective when combined with chemotherapy as it catches the cells deeper inside a tumor — the ones difficult to reach with chemotherapy due to reduced blood supply to the center of the tumor. It is done by inserting a small heat probe into the tumor to kill the tumor cells.[75]

Targeted therapy
In recent years, various molecular targeted therapies have been developed for the treatment of advanced lung cancer. Gefitinib (Iressa) is one such drug, which targets the tyrosine kinase domain of the epidermal growth factor receptor (EGF-R) which is expressed in many cases of non-small cell lung cancer. It was not shown to increase survival, although females, Asians, non-smokers and those with bronchioloalveolar carcinoma appear to derive the most benefit from gefitinib.[15]

Erlotinib (Tarceva), another tyrosine kinase inhibitor, has been shown to increase survival in lung cancer patients[76] and has recently been approved by the FDA for second-line treatment of advanced non-small cell lung cancer. Similar to gefitinib, it appeared to work best in females, Asians, non-smokers and those with bronchioloalveolar carcinoma.[77]

The angiogenesis inhibitor bevacizumab (in combination with paclitaxel and carboplatin) improves the survival of patients with advanced non-small cell lung cancer.[78] However this increases the risk of lung bleeding, particularly in patients with squamous cell carcinoma.

Emerging treatments
The treatment of lung cancer continues to evolve. Advances in cytotoxic drugs,[79] pharmacogenetics[80] and targeted drug design[81] show promise. A number of targeted agents are at the early stages of clinical research, such as cyclo-oxygenase-2 inhibitors,[82] the apoptosis promoter exisulind,[83] proteasome inhibitors,[84] bexarotene[85] and vaccines.[86]

Prognosis
Prognosis depends on the cell type (histology), stage (degree of spread), and the patient's performance status. Overall, the 5-year survival rate is 14%.[4]

Non-small cell lung cancer prognosis
Main article: Non-small cell lung cancer staging
For non-small cell lung cancer, prognosis is poor. Following complete surgical resection of stage IA disease, five-year survival is 67%. With stage IB disease, five-year survival is 57%.[87] The 5-year survival rate of patients with stage IV NSCLC is about 1%.[88]

Small cell lung cancer prognosis
See also: Manchester score
For small cell lung carcinoma, prognosis is also poor. The overall five-year survival for patients with SCLC is about 5%.[4] Patients with extensive-stage SCLC have an average five-year survival rate of less than 1%. The median survival time for limited-stage disease is 20 months, with a five-year survival rate of 20%.[88]

Epidemiology

Lung cancer distribution in the United States.
The population segment most likely to develop lung cancer is the over-fifties who also have a history of smoking. Lung cancer is the second most commonly occurring form of cancer in most western countries, and it is the leading cancer-related cause of death. In the U.S., approximately 213,000 new cases arise each year, and around 160,000 die from it: 114,700 in men and 98,600 in women.[89] Although the rate of men dying from lung cancer is declining in western countries, it is actually increasing for women due to the increased takeup of smoking by this group. Among lifetime non-smokers, men who have never smoked have higher age-standardized lung cancer death rates than women. Of the 80,000 women who are diagnosed with lung cancer in 2006, approximately 70,000 are expected to die from it.[90]

Not all cases of lung cancer are due to smoking, but the role of passive smoking is increasingly being recognized as a risk factor for lung cancer, leading to policy interventions to decrease undesired exposure of non-smokers to others' tobacco smoke. Emissions from automobiles, factories and power plants also pose potential risks.[11][13][91]

Eastern Europe has the highest lung cancer mortality among men, while northern Europe and the U.S. have the highest mortality among women. Lung cancer incidence is less common in developing countries.[92]

History
Lung cancer was extremely rare prior to the advent of cigarette smoking. In 1878, malignant lung tumors made up only 1% of all cancers seen at autopsy; this had risen to 10–15% by the early 1900s.[93] Case reports in the medical literature numbered only 374 worldwide in 1912.[94] A review of autopsies showed that that the incidence of lung cancer had increased from 0.3% in 1852 to 5.66% in 1952.[95] In Nazi Germany, in 1929 physician Fritz Lickint recognized the link between smoking and lung cancer.[93] This led to an aggressive anti-smoking campaign.[96] The British Doctors Study, published in the 1950s, was the first solid epidemiological evidence of the link between lung cancer and smoking.[97]
The connection with radon gas was first recognized among miners in the Ore Mountains near Schneeberg, Saxony. Silver has been mined there since 1470. However these mines are rich in uranium, with accompanying radium and radon gas. Miners developed a disproportionate amount of lung disease, eventually recognized as lung cancer in the 1870s. An estimated 75% of former miners died from lung cancer. Despite this discovery, mining continued into the 1950s due to the USSR's need for uranium.[98]

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^ Murray, N; Turrisi AT (Mar 2006). "A review of first-line treatment for small-cell lung cancer". Journal of Thoracic Oncology 1 (3): 270–278. PMID 17409868.
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^ MacCallum, C; Gillenwater HH (Jul 2006). "Second-line treatment of small-cell lung cancer". Current Oncology Reports 8 (4): 258–264. PMID 17254525.
^ Winton, T; Livingston R, Johnson D et al. (Jun 2005). "Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer". New England Journal of Medicine 352 (25): 2589–2597. PMID 15972865.
^ Douillard, JY; Rosell R, De Lena M et al. (Sep 2006). "Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial". Lancet Oncology 7 (9): 719–727. PMID 16945766.
^ Tsuboi, M; Ohira T, Saji H et al. (Apr 2007). "The present status of postoperative adjuvant chemotherapy for completely resected non-small cell lung cancer" (PDF). Ann Thorac Cardiovasc Surg 13 (2): 73–77. PMID 17505412. Retrieved on 2007-08-14.
^ Horn, L; Sandler AB, Putnam JB Jr, Johnson DH (May 2007). "The rationale for adjuvant chemotherapy in stage I non-small cell lung cancer". Journal of Thoracic Oncology 2 (5): 377–383. PMID 17473651.
^ Wakelee, HA; Schiller JH, Gandara DR (Jul 2006). "Current status of adjuvant chemotherapy for stage IB non-small-cell lung cancer: implications for the New Intergroup Trial". Clinical Lung Cancer 8 (1): 18–21. PMID 16870041.
^ BMJ (Dec 2005). Clinical Evidence Concise. BMJ Publishing Group, 486–488. ISBN 1-905545-00-2.
^ Wagner, H (Jan 1998). "Radiation therapy in the management of limited small cell lung cancer: when, where, and how much?". Chest 113 (Suppl. 1): 92S-100S. PMID 9438697. Retrieved on 2007-08-14.
^ (2005) "Postoperative radiotherapy for non-small cell lung cancer". Cochrane database of systematic reviews (Online) (2): CD002142. DOI:10.1002/14651858.CD002142.pub2. PMID 15846628.
^ Lally, BE; Zelterman D, Colasanto JM et al. (Jul 2006). "Postoperative Radiotherapy for Stage II or III Non–Small-Cell Lung Cancer Using the Surveillance, Epidemiology, and End Results Database". Journal of Clinical Oncology 24 (19): 2998-3006. PMID 16769986.
^ Ng, M; Chong J, Milner A et al. (Jun 2007). "Tolerability of accelerated chest irradiation and impact on survival of prophylactic cranial irradiation in patients with limited-stage small cell lung cancer: review of a single institution's experience". Journal of Thoracic Oncology 2 (6): 506–513. PMID 17545845.
^ Slotman, B; Faivre-Finn C, Kramer G et al. (Aug 2007). "Prophylactic cranial irradiation in extensive small-cell lung cancer". New England Journal of Medicine 357 (7): 664-672. PMID 17699816.
^ Simon, CJ; Dupuy DE, DiPetrillo TA et al. (Apr 2007). "Pulmonary radiofrequency ablation: long-term safety and efficacy in 153 patients". Radiology 243 (1): 268–275. PMID 17392258.
^ Feld, R; Sridhar SS, Shepherd FA et al. (May 2006). "Use of the epidermal growth factor receptor inhibitors gefitinib and erlotinib in the treatment of non-small cell lung cancer: a systematic review". Journal of Thoracic Oncology 1 (4): 367–376. PMID 17409886.
^ Bencardino, K; Manzoni M, Delfanti S et al. (Mar 2007). "Epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of non-small-cell lung cancer: results and open issues". Internal and Emergency Medicine 2 (1): 3–12. PMID 17551677.
^ Sandler, A; Gray R, Perry M et al. (Dec 2006). "Paclitaxel–Carboplatin Alone or with Bevacizumab for Non–Small-Cell Lung Cancer". New England Journal of Medicine 355 (24): 2542-2550. PMID 17167137.
^ Edelman, MJ (Sep 2006). "Novel cytotoxic agents for non-small cell lung cancer". Journal of Thoracic Oncology 1 (7): 752–755. PMID 17409954.
^ Danesi, R; Pasqualetti G, Giovannetti E, Del Tacca M (May 2007). "The role of pharmacogenetics in adjuvant treatment of non-small cell lung cancer". Journal of Thoracic Oncology 2 (5 Suppl.): S27–S30. PMID 17457227.
^ Blackhall, FH; Shepherd FA (Mar 2007). "Small cell lung cancer and targeted therapies". Current Opinion in Oncology 19 (2): 103–108. PMID 17272981.
^ Lee, JM; Mao JT, Krysan K, Dubinett SM (Apr 2007). "Significance of cyclooxygenase-2 in prognosis, targeted therapy and chemoprevention of NSCLC". Future Oncology 2 (2): 149–153. PMID 17381414.
^ Whitehead, Clark M; Keith A Earle, John Fetter et al. (May 2003). "Exisulind-induced Apoptosis in a Non-Small Cell Lung Cancer Orthotopic Lung Tumor Model Augments Docetaxel Treatment and Contributes to Increased Survival". Molecular Cancer Therapeutics 2: 479–488. PMID 12748310. Retrieved on 2007-09-01.
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External links
Lung cancer at the Open Directory Project
Tobacco Smoke and Involuntary Smoking, Summary of Data Reported and Evaluation 2004 by the IARC
Lung Cancer Articles & Information Stop Smoking Articles & Information at National Institutes of Health

To view information on another disease, click on Digestivr Diseases Library.

Digestive Diseases Library

Breast Cancer

2007-09-04T18:12:00.000-07:00

October is Breast Cancer Awareness month. A pink ribbon is worn in rememberance of those who have struggled, or are struggling with breast cancer.

New information:
http://www.king5.com/video/cancerfree-index.html?nvid=208746&shu=1
All breast cancers are not the sameJanuary 15th, 2008
Doctors have known for years that hormone replacement therapy increases the risk of breast cancer. Now, there's new research suggesting that for certain types of cancer, that risk kicks in much earlier: at three years instead of five. Jean Enersen reports.
Click the above link for a short video. (There may or may not be a very short commercial before the information. It is well worth witing to hear!)

http://www.king5.com/video/cancerfree-index.html?nvid=213284&shu=1
Inflammatory breast cancer can come quicklyJanuary 30th, 2008
It's well known one in eight women will develop breast cancer in her lifetime. And most women know the signs to look for. But there's a form of breast cancer that can still take women by surprise. KING 5's Jean Enersen reports.
Click the above link for a short video. (There may or may not be a very short commercial before the information. It is well worth witing to hear!)

Breast cancer
From Wikipedia, the free encyclopedia

Classification & external resources
ICD-10
C 50.
ICD-9
174-175
OMIM
114480
DiseasesDB
1598
MedlinePlus
000913
eMedicine
med/2808
MeSH
D001943

Breast cancer is a cancer of the glandular breast tissue.

Worldwide, breast cancer is the fifth most common cause of cancer death (after lung cancer, stomach cancer, liver cancer, and colon cancer). In 2005, breast cancer caused 502,000 deaths (7% of cancer deaths; almost 1% of all deaths) worldwide. Among women worldwide, breast cancer is the most common cancer and the most common cause of cancer death.[1]

In the United States, breast cancer is the third most common cause of cancer death (after lung cancer and colon cancer). In 2007, breast cancer is expected to cause 40,910 deaths (7% of cancer deaths; almost 2% of all deaths) in the U.S.[2] Among women in the U.S., breast cancer is the most common cancer and the second most common cause of cancer death (after lung cancer). Women in the U.S. have a 1 in 8 lifetime chance of developing invasive breast cancer and a 1 in 33 chance of breast cancer causing their death.[3]

The number of cases has significantly increased since the 1970s, a phenomenon partly blamed on modern lifestyles in the Western world.[4][5]

Excised breast tissue showing a stellate,
pale area of cancer measuring 2cm
across. The tumor could be felt as a hard,
mobile lump before the surgical excision.

Because the breast is composed of identical tissues in males and females, breast cancer also occurs in males, though it is less common.[6]

History

Time line of breast cancer suggesting probable heterogeneity. Primary breast
cancers begin as single (or more) cells which have lost normal regulation of
differentiation and proliferation but remain confined within the basement
membrane of the duct or lobule. As these cells go through several doublings, at
some point they invade through the basement membrane of the duct or lobule and
ultimately metastasize to distant organs.[7]

Breast cancer may be one of the oldest known forms of cancer tumors in humans. The oldest description of cancer (although the term cancer was not used) 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, with a tool called "the fire drill." The writing says about the disease, "There is no treatment."[8] For centuries, physicians described similar cases in their practises, with the same sad conclusion. It wasn't 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. He became known for his Halsted radical mastectomy, a surgical procedure that remained popular up to the 1970s.

Classification
There are numerous ways breast cancer is classified. Like most cancers, breast cancer can be divided into groups based on the tissue of origin, e.g. epithelial (carcinoma) versus stromal (sarcoma). The vast majority of breast cancers arise from epithelial tissue, i.e. they are carcinomas, which can divided further into subclassifications (e.g. DCIS versus LCIS versus papillary carcinoma).

Other pathologically based classifications:

Location of the tumour origin - breast duct (i.e. ductal) versus breast lobule (i.e. lobular).
Histology - see Histologic types section.
Grade of tumour - well-differentiated (looks almost like normal tissue) versus poorly differentiated (does not look like any normal tissue/mass of proliferating cells) versus moderately differentiated (somewhere between poorly differentiated and well-differentiated).
Stage of the tumour.
Immunohistochemical marker status - (ER positive versus ER negative versus HER2/neu positive versus HER2/neu negative), e.g. triple negative breast cancer which is ER negative, PR negative and HER2/neu negative.
TNM classification -

Tumour size/invasiveness - presence of invasion (poorer prognosis) versus in situ (better prognosis).
Nodal status.
Metastases: Presence/absence of metastases.

Histologic types

Carcinomas

in situ
Ductal carcinoma (DCIS) 80%
Lobular carcinoma (LCIS) 20
Invasive
Carcinoma NOS (not otherwise specified)
Lobular carcinoma
Tubular/cribriform carcinoma
Mucinous (colloid)carcinoma
Medullary carcinoma
Papillary carcinoma
Metaplastic carcinoma
Sarcomas
Phyllodes tumour

Clinical categorizations
Breast cancer is occasionally classified clinically (on physical exam findings, (medical) history). Inflammatory breast cancer (IBC) is an example of a clinically classified breast cancer and can be any histologic type.[9]

Symptoms
Early breast cancer can in some cases present as breast pain (mastodynia) or a painful lump. Since the advent of breast mammography, breast cancer is most frequently discovered as an asymptomatic nodule on a mammogram, before any symptoms are present. A lump under the arm or above the collarbone that does not go away may be present. When breast cancer associates with skin inflammation, this is known as inflammatory breast cancer. In inflammatory breast cancer, the breast tumor itself is causing an inflammatory reaction of the skin, and this can cause pain, swelling, warmth, and redness throughout the breast.
Changes in the appearance or shape of the breast can raise suspicions of breast cancer.
Another reported symptom complex of breast cancer is Paget's disease of the breast. This syndrome presents as eczematoid skin changes at the nipple, and is a late manifestation of an underlying breast cancer.

Most breast symptoms do not turn out to represent underlying breast cancer. Benign breast diseases such as fibrocystic mastopathy, mastitis, functional mastodynia, and fibroadenoma of the breast are more common causes of breast symptoms. The appearance of a new breast symptom should be taken seriously by both patients and their doctors, because of the possibility of an underlying breast cancer at almost any age.

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. More 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. Pleural effusions are not uncommon with metastatic breast cancer. Obviously, these symptoms are "non-specific," meaning they can also be manifestations of many other illnesses.

Epidemiologic risk factors and etiology
Epidemiological risk factors for a disease can provide important clues as to the etiology of a disease. The first work 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.[citation needed]
Today, breast cancer, like other forms of cancer, is considered to be the final outcome of multiple environmental and hereditary factors.

Lesions to DNA such as genetic mutations. Exposure to estrogen has been experimentally linked to the mutations that cause breast cancer.[10] Beyond the contribution of estrogen, research has implicated viral oncogenesis and the contribution of ionizing radiation.
Failure of immune surveillance, which usually removes malignancies at early phases of their natural history.
Abnormal growth factor signaling in the interaction between stromal cells and epithelial cells, for example in the angiogenesis necessary to promote new blood vessel growth near new cancers.
Inherited defects in DNA repair genes, such as BRCA1, BRCA2 and p53.

Although many epidemiological risk factors have been identified, the cause of any individual breast cancer is often unknowable. In other words, epidemiological research informs the patterns of breast cancer incidence across certain populations, but not in a given individual. Approximately 5% of new breast cancers are attributable to hereditary syndromes, while no etiology is known for the other 95% of cases.[11]

Age
The risk of getting breast cancer increases with age. A woman who lives to age 90 has a lifetime risk of about 14.3%, or one in seven.[12] The probability of breast cancer rises with age, but breast cancer tends to be more aggressive when it occurs in younger people. One type of breast cancer that is especially aggressive and that occurs disproportionately in younger people is inflammatory breast cancer. It is initially staged as Stage IIIb or Stage IV. It also is unique because it often does not present with a lump, so it is often undetected by mammography or ultrasound. It presents with the signs and symptoms of a breast infection like mastitis, and the treatment is usually a combination of surgery, radiation, and chemotherapy.
Sex
Men have a lower risk of developing breast cancer (approximately 1.08 per 100,000 men per year), but this risk appears to be rising.[13]
Heredity
In 5% of breast cancer cases, there is a strong inherited familial risk.[14] Two autosomal dominant genes, BRCA1 and BRCA2, account for most of the cases of familial breast cancer. Family members who harbor mutations in these genes have a 60% to 80% risk of developing breast cancer in their lifetimes.[14] Other associated malignancies include ovarian cancer and pancreatic cancer. If a mother or a sister was diagnosed breast cancer, the risk of a hereditary ‘’’BRCA1’’’ or ‘’’BRCA2’’’ gene mutation is about 2-fold higher than those women without a familial history. In addition to the BRCA genes associated with breast cancer, the presence of NBR2, near breast cancer gene 1, has been discovered, and research into its contribution to breast cancer pathogenesis is ongoing.[15] Commercial testing for ‘’’BRCA1’’’ and ‘’’BRCA2’’’ gene mutations has been available since at least 2004. Genetic testing for BRCA gene mutations is conducted exclusively by Myriad Genetics, located in Salt Lake City [Utah].
Diet
Dietary influences have been proposed and examined, and recent research suggests that low-fat diets may significantly decrease the risk of breast cancer as well as the recurrence of breast cancer.[16] Another study showed no contribution of dietary fat intake on the incidence of breast cancer in over 300,000 women.[17] A randomized controlled study of the consequences of a low-fat diet, the Women's Health Initiative, failed to show a statistically significant reduction in breast cancer incidence in the group assigned to a low-fat diet, although the authors did find evidence of a benefit in the subgoup of women who followed the low-fat diet in a strict manner.[18] Another randomized trial, the Nurses' Health Study II, found increased breast cancer incidence in premenopausal women only, with higher intake of animal fat, but not vegetable fat. Taken as a whole, these results point to a possible association between dietary fat intake and breast cancer incidence, though these interactions are hard to measure in large groups of women.

In a study published in the Journal of the American Medical Association, biomedical investigators found that Brassica vegetable intake (broccoli, cauliflower, cabbage, kale and Brussels sprouts) was inversely related to breast cancer development. The relative risk among women in the highest decile of Brassica vegetable consumption (median, 1.5 servings per day) compared to the lowest decile (virtually no consumption) was 58%. That is, women who consumed the most Brassica vegetables were 58% less likely to develop breast cancer.[19]

A significant environmental effect is likely responsible for the different rates of breast cancer incidence between countries with different dietary customs. Researchers have long measured that breast cancer rates in an immigrant population soon come to resemble the rates of the host country after a few generations. The reason for this is speculated to be immigrant uptake of the host country diet. The prototypical example of this phenomenon is the changing rate of breast cancer after the arrival of Japanese immigrants to America.[20]

Alcohol
Alcohol appears to increase the risk of breast cancer, though meaningful increases are limited to higher alcohol intake levels. Breast cancer constitutes about 7.3% of all cancers.[21] Among women, breast cancer comprises 60% of alcohol-attributable cancers.[22] The UK's Review of Alcohol: Association with Breast Cancer concludes that "studies confirm previous observations that there appears to be an association between alcohol intake and increased risk of breast cancer in women. On balance, there was a weak association between the amount of alcohol consumed and the relative risk."[23]

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) concludes that "Chronic alcohol consumption has been associated with a small (averaging 10 percent) increase in a woman's risk of breast cancer."[24][25][26][27]
According to these studies, the risk appears to increase as the quantity and
duration of alcohol consumption increases. Other studies, however, have found no evidence of such a link.[28][29][30]
The Committee on Carcinogenicity of Chemicals in Food, Consumer Products
Non-Technical Summary concludes, "the new research estimates that a woman drinking an average of two units of alcohol per day has a lifetime risk of developing breast cancer 8% higher than a woman who drinks an average of one unit of alcohol per day.[31] The risk of breast cancer further increases with each additional drink consumed per day. The research also concludes that approximately 6% (between 3.2% and 8.8%) of breast cancers reported in the UK each year could be prevented if drinking was reduced to a very low level (i.e. less than 1 unit/week)." A review
article from JAMA also found that breast cancer incidence seems to increase with
increasing alcohol consumption.[32] It has been reported that "two drinks daily increase the risk of getting breast cancer by about 25 percent" (NCI), but the evidence is inconsistent. The Framingham study has carefully tracked individuals since the 1940s. Data from that research found that drinking alcohol moderately did not increase breast cancer risk (Wellness Facts). Similarly, research by the Danish National Institute for Public Health found that moderate drinking had virtually no effect on breast cancer risk.[33] One study suggests that women who frequently drink red wine may have an increased risk of developing breast cancer.[34]
"Folate intake counteracts breast cancer risk associated with alcohol
consumption"[35] and "women who drink alcohol and have a high folate intake are not at increased risk of cancer."[36] Those who have a high (200 micrograms or more per day) level of folate (folic acid or Vitamin B9) in their diet are not at increased risk of breast cancer compared to those who abstain from alcohol.[37]
Foods rich in folate include citrus fruits, citrus juices, dark green leafy
vegetables (such as spinach), dried beans, and peas. Vitamin B9 can also be
taken in a multivitamin pill.

Obesity
Gaining weight after menopause can increase a woman's risk. A recent study found that putting on 9.9kg (22lbs) after menopause increased the risk of developing breast cancer by 18%.[38]
Hormones
Persistently increased blood levels of estrogen are associated with an increased risk of breast cancer, as are increased levels of the androgens androstenedione and testosterone (which can be directly converted by aromatase to the estrogens estrone and estradiol, respectively). Increased blood levels of progesterone are associated with a decreased risk of breast cancer in premenopausal women.[39] A number of circumstances which increase exposure to endogenous estrogens including not having children, delaying first childbirth, not breastfeeding, early menarche (the first menstrual period) and late menopause are suspected of increasing lifetime risk for developing breast cancer.[40]
Hormonal contraceptives may produce a slight increase in the risk of breast cancer diagnosis among current and recent users, but this appears to be a short-term effect. In 1996 the largest collaborative reanalysis of individual data on over 150,000 women in 54 studies of breast cancer found a relative risk (RR) of 1.24 of breast cancer diagnosis among current combined oral contraceptive pill users; 10 or more years after stopping, no difference was seen. Further, the cancers diagnosed in women who had ever used hormonal contraceptives were less advanced than those in nonusers, raising the possibility that the small excess among users was due to increased detection.[41][42] The relative risk of breast cancer diagnosis associated with current and recent use of hormonal contraceptives did not appear to vary with family history of breast cancer.[43]
Data exist from both observational and randomized clinical trials regarding the association between postmenopausal hormone replacement therapy (HRT) and breast cancer. The largest meta-analysis (1997) of data from 51 observational studies, indicated a relative risk of breast cancer of 1.35 for women who had used HRT for 5 or more years after menopause. The estrogen-plus-progestin arm of the Women's Health Initiative (WHI), a randomized controlled trial, which randomized more than 16,000 postmenopausal women to receive combined hormone therapy or placebo, was halted early (2002) because health risks exceeded benefits. One of the adverse outcomes prompting closure was a significant increase in both total and invasive breast cancers (RR = 1.24) in women randomized to receive estrogen and progestin for an average of 5 years. HRT-related breast cancers had adverse prognostic characteristics (more advanced stages and larger tumors) compared with cancers occurring in the placebo group, and HRT was also associated with a substantial increase in abnormal mammograms. Short-term use of hormones for treatment of menopausal symptoms appears to confer little or no breast cancer risk.[43]

Environmental causes

Tobacco
Most studies have not found an increased risk of breast cancer from active tobacco smoking, although a number of studies suggest an increased risk of breast cancer in both active smokers and those exposed to secondhand smoke compared to women who reported no exposure to secondhand smoke.[44]
Radiation
Women who have received high-dose ionizing radiation to the chest (for example, as treatments for other cancers) have a relative risk of breast cancer between 2.1 to 4.0.[44]
Impact of environmental estrogenic mimics
Although environmental exposures are not generally cited as risk factors for the disease (except for diet, pharmaceuticals and radiation), a substantial and growing body of evidence indicates that exposures to certain toxic chemicals and hormone-mimicking compounds including chemicals used in pesticides, cosmetics and cleaning products contribute to the development of breast cancer. A recent Canadian study concluded that female farm workers are three times more likely to have breast cancer.[45] The increasing prevalence of these substances in the environment may explain the increasing incidence of breast cancer, though direct evidence is sparse.
Dioxins
Although not well-quantified, there has long been a concern about risk associated with environmental estrogenic compounds, such as dioxins. [citation needed]
Light levels
Researchers at the National Cancer Institute and National Institute of Environmental Health Sciences have concluded a study that suggests that artificial light during the night can be a factor for breast cancer.[46]
Viral breast cancer pathogenesis research
Humans are not the only mammals prone to breast cancer. Some strains of mice, namely the house mouse (Mus domesticus) are prone to breast cancer which is caused by infection with the mouse mammary tumour virus (MMTV or "Bittner virus" for its discoverer Hans Bittner), by random insertional mutagenesis. This finding is taken to mean that a viral etiology of human breast cancer is at least possible, though there is no definitive evidence to support the claim that MMTV causes human breast cancer. For example, there may be critical differences between cancer pathogenesis in mice and people. The understanding of the role of MMTV or other viruses in human breast cancer is preliminary as of May 2007.

Factors with minimal or no impact on breast cancer risk

Abortion
Main article: Abortion-breast cancer hypothesis
Studies in rats[47] led to speculation that abortion may increase the risk of breast cancer because of hormones initiating breast tissue growth in early pregnancy. Some early interview[48] and record[49] based case-control studies indicated a possible correlation, but more recent record based studies[50][51][52] and a large meta-analysis[53] study do not support this association. The subject was examined by a National Cancer Institute (NCI) workshop in 2003, in response to the Bush Administration's alteration of the NCI's website to emphasize studies indicating a potential link.[54] The NCI expert panel concluded, with the strongest level of evidence, that induced abortion is not associated with an increased breast cancer risk.[55]
Deodorants
Much has been made of the possible contribution of aluminum-containing underarm antiperspirants to the incidence of breast cancer, since the most common location of a breast cancer is the upper outer quadrant of the breast. Aluminum salts, such as those used in anti-perspirants, have recently been classified as metalloestrogens. In research published in the Journal of Applied Toxicology, Dr. Philippa D. Darbre of the University of Reading has shown that aluminum salts increase estrogen-related gene expression in human breast cancer cells grown in the laboratory.[56][57][58] Fortunately, this in-vitro association between aluminum salts and estrogen activity does not translate into an increased risk of breast cancer in humans. The lack of association between underarm deodorants and breast cancer has been the subject of a number of research articles.[59][60]
Fertility treatments
There is no persuasive connection between fertility medications and breast cancer.[61]
Phytoestrogens and soy
Phytoestrogens such as found in soybeans have been extensively studied in animal and human in-vitro and epidemiological studies. The literature support the following conclusions:

Plant estrogen intake, such as from soy products, in early adolescence may
protect against breast cancer later in life.[62]
Plant estrogen intake later in life is not likely to influence breast cancer
incidence either positively or negatively.[63]
It seems reasonable to conclude that soybean-based phytoestrogens are not a major
contributor to the incidence of breast cancer.

Prevention in high-risk individuals

Prophylactic oophorectomy
Prophylactic oophorectomy (removal of ovaries), in high-risk individuals, when child-bearing is complete, reduces the risk of developing breast cancer by 60%, as well as reducing the risk of developing ovarian cancer by 96%.[64]
Prophylactic mastectomy
Bilateral prophylactic mastectomies have been shown to prevent breast cancer in high-risk individuals, such as patients with BRCA1 or BRCA2 gene mutations.
Medications
Hormonal therapy has been used for chemoprevention in individuals at high risk for breast cancer. In 2002, a clinical practice guideline by the U.S. Preventive Services Task Force (USPSTF) recommended "clinicians discuss chemoprevention with women at high risk for breast cancer and at low risk for adverse effects of chemoprevention" with a grade B recommendation.[65][66]
Selective estrogen receptor modulators (SERMs)
The guidelines were based on studies of SERMs from the MORE, BCPT P-1, and Italian trials. In the MORE trial, the relative risk reduction for raloxifene was 76%.[67] The P-1 preventative study demonstrated that tamoxifen can prevent breast cancer in high-risk individuals. The relative risk reduction was up to 50% of new breast cancers, though the cancers prevented were more likely estrogen-receptor positive (this is analogous to the effect of finasteride on the prevention of prostate cancer, in which only low-grade prostate cancers were prevented).[68][69]
The Italian trial showed benefit from tamoxifen.[70]
Additional randomized controlled trials have been published since the guidelines. The IBIS trial found benefit from tamoxifen. [71]In 2006, the NSABP STAR trial demonstrated that raloxifene had equal efficacy in preventing breast cancer compared with tamoxifen, but that there were fewer side effects with raloxifene.[72] The RUTH Trial concluded that "benefits of raloxifene in reducing the risks of invasive breast cancer and vertebral fracture should be weighed against the increased risks of venous thromboembolism and fatal stroke".[73]
Raloxifene is only FDA-approved for osteoporosis as of May 2007.

Screening

X-ray mammography
Due to the high incidence of breast cancer among older women, screening is now recommended in many countries. Recommended screening methods include breast self-examination and mammography. Mammography has been estimated to reduce breast cancer-related mortality by 20-30%.[74] Routine (annual) mammography of women older than age 40 or 50 is recommended by numerous organizations as a screening method to diagnose early breast cancer and has demonstrated a protective effect in multiple clinical trials.[75] The evidence in favor of mammographic screening comes from eight randomized clinical trials from the 1960s through 1980s. Many of these trials have been criticised for methodological errors, and the results were summarized in a review article published in 1993.[76]
CAD Systems (Computer Aided Diagnosis) may help radiologists to evaluate X-ray images to detect breast cancer in an early stage. CAD is especially established in US and the Netherlands. It is used in addition to the human evaluation of the diagnostician.
Improvements in mortality due to screening are hard to measure; similar difficulty exists in measuring the impact of Pap smear testing on cervical cancer, though worldwide, the impact of that test is likely enormous. Nationwide mortality due to cancer before and after the institution of a screening test is a surrogate indicator about the effectiveness of screening, and results of mammography are favorable.

Normal (left) versus cancerous (right) mammography image.
The U.S. National Cancer Institute recommends screening mammography with a baseline mammogram at age 35, mammograms every two years beginning at age 40, and then annual mammograms beginning at age 50. In the UK, women are invited for screening once every three years beginning at age 50. Women with one or more first-degree relatives (mother, sister, daughter) with premenopausal breast cancer should begin screening at an earlier age. It is usually suggested to start screening at an age that is 10 years less than the age at which the relative was diagnosed with breast cancer.
Part of the difficulty in interpreting mammograms in younger women stems from the problem of breast density. Radiographically, a dense breast has a preponderance of glandular tissue, and younger age or estrogen hormone replacement therapy contribute to mammographic breast density. After menopause, the breast glandular tissue gradually is replaced by fatty tissue, making mammographic interpretation much more accurate. Some authors speculate that part of the contribution of estrogen hormone replacement therapy to breast cancer mortality arises from the issue of increased mammographic breast density. Breast density is an independent adverse prognostic factor on breast cancer prognosis. Several scientific groups however have expressed concern about the public's perceptions of the benefits of breast screening.[77] In 2001, a controversial review published in The Lancet claimed that there is no reliable evidence that screening for breast cancer reduces mortality.[78] The results of this study were widely reported in the popular press.[79] False positives are a major problem of mammographic breast cancer screening. Data reported in the UK Million Woman Study indicates that if 134 mammograms are performed, 20 women will be called back for suspicious findings, and four biopsies will be necessary, to diagnose one cancer. Recall rates are higher in the U.S. than in the UK.[80] The contribution of mammography to the early diagnosis of cancer cannot be overstated, but it comes at a huge financial and psychological cost to the women found to have a nodule. In general, digital mammography and computer-aided mammography have increased the sensitivity of mammograms, but at the cost of more numerous false positive results.
Mammography is still the modality of choice for screening of early breast cancer, since it is relatively fast, reasonably accurate, and widely available in developed countries. Breast cancers detected by mammography are usually much smaller (earlier stage) than those detected by patients or doctors as a breast lump.

Breast MRI
Magnetic resonance imaging (MRI) has been shown to detect cancers not visible on mammograms, but has long been regarded to have disadvantages. For example, although it is 27-36% more sensitive, it is less specific than mammography.[81] As a result, MRI studies will have more false positives (up to 5%), which may have undesirable financial and psychological costs. It is also a relatively expensive procedure, and one which requires the intravenous injection of a chemical agent to be effective. Proposed indications for using MRI for screening include:[82]

Strong family history of breast cancer
Patients with BRCA-1 or BRCA-2
oncogene mutations
Evaluation of women with breast implants
History of previous lumpectomy or breast biopsy surgeries
Axillary metastasis with an unknown primary tumor
Very dense or scarred breast tissue

However, two studies published in 2007 demonstrated the strengths of MRI-based screening:

In March 2007, an article published in the New England Journal of Medicine demonstrated that in 3.1% of patients with breast cancer, whose contralateral breast was clinically and mammographically tumor-free, MRI could detect breast cancer. Sensitivity for detection of breast cancer in this study was 91%, specificity 88%.[83]
In August 2007, an article published in The Lancet compared MRI breast cancer screening to conventional mammographic screening in 7,319 women. MRI screening was highly more sensitive (97% in the MRI group vs. 56% in the mammography group) in recognizing early high-grade Ductal Carcinoma in situ (DCIS), the most important precursor of invasive carcinoma. Despite the high sensitivity, MRI screening had a positive predictive value of 52%, which is totally accepted for cancer screening tests.[84] The author of a comment published in the same issue of The Lancet concludes that "MRI outperforms mammography in tumour detection and diagnosis."[85]

Breast ultrasound
Ultrasound alone is not usually employed as a screening tool but it is a useful additional tool for the characterization of palpable tumours and directing image-guided biopsies. U-Systems is a US-based company that is selling a breast-cancer detection system using ultrasound that is fully-automated. Using an ultrasound allows a look at dense breast tissue which is not possible with digital mammmography. It is closely correlated with the digital mammography. The other significant advantage over digital mammography is that it is a pain-free procedure.

Breast self-exam
Breast self-exam was widely discussed in the 1990s as a useful modality for detecting breast cancer at an earlier stage of presentation. A large clinical trial in China reduced enthusiasm for breast self-exam. In the trial, reported in the Journal of the National Cancer Institute first in 1997 and updated in 2002, 132,979 female Chinese factory workers were taught by nurses at their factories to perform monthly breast self-exam, while 133,085 other workers were not taught self-exam. The women taught self-exam tended to detect more breast nodules, but their breast cancer mortality rate was no different from that of women in the control group. In other words, women taught breast self-exam were mostly likely to detect benign breast disease, but were just as likely to die of breast cancer.[86] An editorial in the Journal of the National Cancer Institute reported in 2002, "Routinely Teaching Breast Self-Examination is Dead. What Does This Mean?"[87]

Diagnosis
Breast cancer is diagnosed by the pathological (microscopic) examination of surgically removed breast tissue. A number of procedures can obtain tissue or cells prior to definitive treatment for histological or cytological examination. Such procedures include fine-needle aspiration, nipple aspirates, ductal lavage, core needle biopsy, and local surgical excisional biopsy. These diagnostic steps, when coupled with radiographic imaging, are usually accurate in diagnosing a breast lesion as cancer. Occasionally, pre-surgical procedures such as fine needle aspirate may not yield enough tissue to make a diagnosis, or may miss the cancer entirely. Imaging tests are sometimes used to detect metastasis and include chest X-ray, bone scan, CT, MRI, and PET scanning. While imaging studies are useful in determining the presence of metastatic disease, they are not in and of themselves diagnostic of cancer. Only microscopic evaluation of a biopsy specimen can yield a cancer diagnosis. Ca 15.3 (carbohydrate antigen 15.3, epithelial mucin) is a tumor marker determined in blood which can be used to follow disease activity over time after definitive treatment. Blood tumor marker testing is not routinely performed for the screening of breast cancer, and has poor performance characteristics for this purpose.

Staging
Breast cancer is staged according to the TNM system, updated in the AJCC Staging Manual, now on its sixth edition. Prognosis is closely linked to results of staging, and staging is also used to allocate patients to treatments both in clinical trials and clinical practice.

Summary of stages:

Stage 0 - Carcinoma in situ
Stage I - Tumor (T) does not involve axillary lymph nodes (N).
Stage IIA – T 2-5 cm, N negative, or T <2> 5 cm, N negative, or T 2-5 cm and N positive (<> 5 cm, N positive, or T 2-5 cm with 4 or more axillary nodes
Stage IIIB – T has penetrated chest wall or skin, and may have spread to <> 10 axillary N, 1 or more supraclavicular or infraclavicular N, or internal mammary N.
Stage IV – Distant metastasis (M)

Breast lesions are examined for certain markers, notably sex steroid hormone receptors. About two thirds of postmenopausal breast cancers are estrogen receptor positive (ER+) and progesterone receptor positive (PR+).[88] Receptor status modifies the treatment as, for instance, only ER-positive tumors, not ER-negative tumors, are sensitive to hormonal therapy.
The breast cancer is also usually tested for the presence of human epidermal growth factor receptor 2, a protein also known as HER2, neu or erbB2. HER2 is a cell-surface protein involved in cell development. In normal cells, HER2 controls aspects of cell growth and division. When activated in cancer cells, HER2 accelerates tumor formation. About 20-30% of breast cancers overexpress HER2. Those patients may be candidates for the drug trastuzumab, both in the postsurgical setting (so-called "adjuvant" therapy), and in the metastatic setting.[89]

Treatment personalization with gene expression profiling
Recently, the acceleration of gene expression profiling research has made available additional markers to predict disease recurrence. Beyond conventional TNM staging, doctors can now order a gene expression profile on tumors to predict whether a breast cancer patient will have a high chance of developing breast cancer again. There are currently 2 commercial tests on the market, MammaPrint and Oncotype DX. Oncotype DX is not used in every clinical setting; for example, in a patient with positive lymph nodes who is a candidate for chemotherapy, the test would not change therapy decisions. The most useful setting for Oncotype DX testing is where there are negative lymph nodes, and the benefit of chemotherapy is felt to be small. In up to 10% of patients, there will be disease recurrences, but treating every patient with chemotherapy is overkill. In this setting, a high-risk score on the Oncotype DX can help doctors decide whether to recommend chemotherapy.

Treatment

The mainstay of breast cancer treatment is surgery when the tumor is localized, with possible adjuvant hormonal therapy (with tamoxifen or an aromatase inhibitor), chemotherapy, and/or radiotherapy. At present, the treatment recommendations after surgery (adjuvant therapy) follow a pattern. This pattern is subject to change, as every two years, a worldwide conference takes place in St. Gallen, Switzerland, to discuss the actual results of worldwide multi-center studies. Depending on clinical criteria (age, type of cancer, size, metastasis) patients are roughly divided to high risk and low risk cases, with each risk category following different rules for therapy. Treatment possibilities include radiation therapy, chemotherapy, hormone therapy, and immune therapy.

In planning treatment, doctors can also use PCR tests like Oncotype DX or microarray tests like MammaPrint that predict breast cancer recurrence risk based on gene expression. In February 2007, the MammaPrint test became the first breast cancer predictor to win formal approval from the Food and Drug Administration. This is a new gene test to help predict whether women with early-stage breast cancer will relapse in 5 or 10 years, this could help influence how aggressively the initial tumor is treated.[90]

Surgery
Depending on the staging and type of the tumor, just a lumpectomy (removal of the lump only) may be all that is necessary, or removal of larger amounts of breast tissue may be necessary. Surgical removal of the entire breast is called mastectomy. Lumpectomy techniques are increasingly utilized for breast-conservation cancer surgery.
However, mastectomy may be the preferred treatment in certain instances:

Two or more tumors exist in different areas of the breast (a "multifocal"
cancer).
The breast has previously received radiation (XRT) treatment.
The tumor is large relative to the size of the breast.
The patient has had scleroderma or another disease of the connective tissue, which can complicate XRT treatment.
The patient lives in an area where XRT is inaccessible.
The patient is apprehensive about the risk of local recurrence after lumpectomy.

Standard practice requires the surgeon to establish that the tissue removed in the operation has margins clear of cancer, indicating that the cancer has been completely excised. If the removed tissue does not have clear margins, further operations to remove more tissue may be necessary. This may sometimes require removal of part of the pectoralis major muscle, which is the main muscle of the anterior chest wall.

During the operation, the lymph nodes in the axilla are also considered for removal. In the past, large axillary operations took out 10 to 40 nodes to establish whether cancer had spread. This had the unfortunate side effect of frequently causing lymphedema of the arm on the same side, as the removal of this many lymph nodes affected lymphatic drainage. More recently, the technique of sentinel lymph node (SLN) dissection has become popular, as it requires the removal of far fewer lymph nodes, resulting in fewer side effects. The sentinel lymph node is the first node that drains the tumor, and subsequent SLN mapping can save 65-70% of patients with breast cancer from having a complete lymph node dissection for what could turn out to be a negative nodal basin. Advances in Sentinel Lymph Node mapping over the past decade have increased the accuracy of detecting Sentinel Lymph Node from 80% using blue dye alone to between 92% and 98% using combined modalities.[91]
SLN biopsy is indicated for patients with T1 and T2 lesions (<5cm)[91]

Radiation therapy
Radiation therapy involves using high-powered X-rays or gamma rays (XRT) that precisely target the area being treated. These X-rays or gamma rays are very effective in destroying the cancer cells that might recur where the tumor was removed. The X-rays are delivered by a machine called a linear Accelerator or LINAC. Alternatively, the use of implanted radioactive catheters (brachytherapy), similar to those used in prostate cancer treatment, is being evaluated. Radiation therapy for breast cancer is usually performed after surgery and is an essential component of breast-conserving therapy. The purpose of radiation is to reduce the chance that the cancer will recur.

Radiation therapy eliminates the microscopic cancer cells that may remain near the area where the tumor was surgically removed. The dose of radiation must be strong enough to ensure the elimination of cancer cells. However, radiation affects normal cells and cancer cells alike, causing some damage to the normal tissue around where the tumor was. Healthy tissue can repair itself, while cancer cells do not repair themselves as well as normal cells. For this reason, radiation treatments are given over an extended period, enabling the healthy tissue to heal. Treatments are typically given over a period of five to seven weeks, performed five days a week. Each treatment takes about 15 minutes.
Although radiation therapy can reduce the chance of breast cancer recurrence, it is much less effective in prolonging patient survival. According to a review of six studies by the National Cancer Institute, none of them found a survival benefit for radiation therapy.[92] Patients who are unable to have radiation therapy after lumpectomy should consult with a surgeon who understands this research and who believes that lumpectomy (or partial mastectomy) alone is a reasonable treatment option.

Indications for radiation
Indications for radiation treatment are constantly evolving. Patients treated in Europe have been more likely in the past to be recommended adjuvant radiation after breast cancer surgery. Radiation therapy is usually recommended for all patients who had (lumpectomy, quadrant-resection). Radiation therapy is usually not indicated in patients with advanced (stage IV disease) except for palliation of symptoms like bone pain.
In general recommendations would include:

As part of breast conserving therapy when the whole breast is not removed (lumpectomy or wide local excision)
After mastectomy: Patients with higher chances of cancer recurring because of conditions such as a large primary tumor or involvement of four or more lymph nodes.

Other factors which may influence adding adjuvant radiation therapy:

Tumor close to or involving the margins on pathology specimen
Multiple areas of tumor (multicentric disease)
Microscopic invasion of lymphatic or vascular tissues
Patients with <4>
Inadequate numbers of axillary LN sampled

Types of radiotherapy

Radiotherapy can be delivered in many ways. The most common delivery method is linear accelerators.
There have been many improvements in the techniques that deliver radiation to the breast. One such new technology is using IMRT (intensity modulated radiation therapy), in which the radiation oncologist can change the shape and intensity of the radiation beam at different points across and inside the breast. This allows for a more focused beam of radiation directed at the tumor cells and leaves most of the healthy tissue unaffected by the radiation.
Another new procedure involves a type of brachytherapy, where a radioactive source is temporarily placed inside the breast in direct contact with the tumor bed (area where tumor was removed). This technique is called a Mammosite and is currently undergoing clinic trials.
New technology has also allowed more precise delivery of radiotherapy in a portable fashion — for example in the operating theatre. Targeted intraoperative radiotherapy (TARGIT)[93] is a method of delivering therapeutic radiation from within the breast using a portable X-ray generator called Intrabeam. It is undergoing clinical trials in several countries to test whether it can replace the whole course of radiotherapy in selected patients.[94] It may also be able provide a much better boost dose to the tumor bed and appears to provide superior control.[95] This will be tested in a TARGIT-B trial.[96]

Side effects of radiation therapy
The side effects of radiation have decreased considerably over the past decades. Aside from general fatigue caused by the healthy tissue repairing itself, there will probably be no side effects at all. Some patients develop a suntan-like change in skin color in the exact area being treated. As with a suntan, this darkening of the skin will fade with time. Other side effects experienced with radiation include the fact that radiation therapy can and often does cause permanent changes in the color and texture of skin, in addition to: reddening of the skin muscle stiffness mild swelling tenderness in the area long-term shrinking of the irradiated breast The use of adjuvant radiation has significant potential effects if the patient has to later undergo breast reconstruction surgery. Fibrosis of chest wall skin from radiation negatively affects skin elasticity and makes tissue expansion techniques difficult. Traditionally most patients are advised to defer immediate breast reconstruction when adjuvant radiation is planned and are most often recommended surgery involving autologous tissue reconstruction rather then breast implants.

Systemic therapy
Systemic therapy uses medications to treat cancer cells throughout the body. Any combination of systemic treatments may be used to treat breast cancer. Systemic treatments include chemotherapy, immune therapy, and hormonal therapy.
Chemotherapy
Chemotherapy (drug treatment for cancer) may used before surgery, after surgery, or instead of surgery in those patients who are unsuitable for surgery.
See breast cancer chemotherapy.
Hormonal treatment
Patients with estrogen receptor positive tumors will typically receive hormonal therapy after chemotherapy is completed. Typical hormonal treatments include:

Tamoxifen is typically given to premenopausal women to inhibit the estrogen
receptors
Aromatase inhibitors are typically given to postmenopausal women to
lower the amount of estrogen in their systems
GnRH-analogues
ovarian ablation or
suppression is used in premenopausal women

Targeted therapy
In patients whose cancer expresses an over-abundance of the HER2 protein, a monoclonal antibody known as trastuzumab (Herceptin ®) is used to block the activity of the HER2 protein in breast cancer cells, slowing their growth. In the advanced cancer setting, trastuzumab use in combination with chemotherapy can both delay cancer growth as well as improve the recipient's survival.[97] More recently, several clinical trials have also confirmed that in the adjuvant setting i.e. postoperative following breast cancer surgery, the use of trastuzumab for up to one year also delays the recurrence of breast cancer and improves survival.[98][99][100]
Antiangiogenic therapy
A commercially available monoclonal antibody that blocks the activation of the VEGF receptor, bevacizumab, underwent testing in a randomized clinical trial whose preliminary results were announced by the National Cancer Institute in 2005.[101] The preliminary data indicated that bevacizumab delays disease progression for up to five months over conventional chemotherapy, but survival was no better. Genentech, manufacturer of bevacizumab, has filed a supplemental biological application with the FDA for approval of bevacizumab in the setting of metastatic breast cancer, on the strength of the improvement in progression-free survival.
Preclinical

Protein tyrosine phosphatase 1B (PTP1B) In the March 2007,
edition of the scientific journal, Nature Genetics, researchers from Canada's McGill University reported that they have developed a potential drug target for treating up to 40 percent of breast cancers by blocking an enzyme called protein tyrosine phosphatase 1B (PTP1B), which has been implicated in the onset of breast cancer in mouse models of the disease.[102] Elevated levels of PTP1B have also been found in diabetes and obesity. A drug to block the activity of PTP1B is under development by Merck, and was found to delay the development of breast tumors and prevent lung cancer up to two months from the administration of the drug. The researchers hope to continue further research in mouse models which are also HER-2 positive (responsive to Herceptin) so that the drug could benefit a significant population of women.[103]
Flax seeds
Preliminary research into flax seeds indicate that flax can significantly change breast cancer growth and metastasis, and enhance the inhibitory effect of tamoxifen on estrogen-dependent tumors.[104][105][106][107]

Traditional Chinese medicine
The use of traditional Chinese medicine to treat breast cancer has been claimed, but no successful clinical trials have yet been reported.

Psychological aspects of breast cancer diagnosis and treatment
The emotional impact of cancer diagnosis, symptoms, treatment, and related issues can be severe. Most larger hospitals are associated with cancer support groups which can help patients cope with the many issues that come up in a supportive environment with other people with experience with similar issues. Online cancer support groups are also very beneficial to cancer patients, especially in dealing with uncertainty and body-image problems inherent in cancer treatment.

Prognosis
There are several prognostic factors associated with breast cancer. Stage is the most important, as it takes into consideration local involvement, lymph node status and whether metastatic disease is present. The higher the stage at diagnosis, the worse the prognosis. Breast cancer patients whose lymph nodes are cancer-free have a much better prognosis than those whose lymph nodes are positive for cancer.

The presence of estrogen and progesterone receptors in the cancer cell is another important prognostic factor which may guide treatment. Hormone receptor positive breast cancer is usually associated with much better prognosis compared to hormone negative breast cancer.
HER2/neu status has also been described as a prognostic factor. Patients whose cancer cells are positive for HER2/neu have more aggressive disease and may be treated with trastuzumab, a monoclonal antibody that targets this protein.

Breast cancer in males
Less than 1% of breast cancers occur in men, and incidence is about 1 in 100,000. Men with gynaecomastia do not have a higher risk of developing breast cancer.[108] There may be an increased incidence of breast cancer in men with prostate cancer. The prognosis, even in stage I cases, is worse in men than in women.[109] The treatment of men with breast cancer is similar to that in older women. Since the male breast tissue is confined to the area directly behind the nipple, treatment for males has usually been a mastectomy with axillary surgery. This may be followed by adjuvant radiotherapy, hormone therapy (such as tamoxifen), or chemotherapy.

Breast cancer metastasis
Most people understand breast cancer as something that happens in the breast. However it can metastasise (spread) via lymphatics to nearby lymph nodes, usually those under the arm. That is why surgery for breast cancer always involves some type of surgery for the glands under the arm — either axillary clearance, sampling, or sentinel node biopsy.

Breast cancer can also spread to other parts of the body via blood vessels. So it can spread to the lungs, pleura (the lining of the lungs), liver, brain, and most commonly to the bones. Seventy percent of the time that breast cancer spreads to other locations, it spreads to bone, especially the vertebrae and the long bones of the arms, legs, and ribs. Breast cancer cells "set up house" in the bones and form tumors. Usually when breast cancer spreads to bone, it eats away healthy bone, causing weak spots, where the bones can break easily. That is why breast cancer patients are often seen wearing braces or using a wheelchair, and why they complain about aching bones.
When breast cancer is found in bones, it has usually spread to more than one site. At this stage, it is treatable, often for many years, but it is not curable. Like normal breast cells, these tumors in the bone often thrive on female hormones, especially estrogen. Therefore, the doctor often treats the patient with medicines that lower her estrogen levels.

Breast cancer awareness

In the month of October, breast cancer is recognized by 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 the cancer.

Pink for October is an initiative started by Matthew Oliphant, which asks that any sites willing to help make people aware of breast cancer, change their template or layout to include the color pink, so that when visitors view the site, they see that the majority of the site is pink. Then after reading a short amount of information about breast cancer, or being redirected to another site, they are aware of the disease itself.

See also
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
Alcohol and cancer
Mammography Quality Standards Act
National Breast Cancer Coalition
National Comprehensive Cancer Network
Breast Cancer Action
Breakthrough Breast Cancer
Barron Lerner (Physician)
William Stewart Halsted (Radical Masectomy)
International Agency for Research on Cancer
The Hormone Foundation
Susan G. Komen for the Cure

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[edit] External links
Breast cancer at the Open Directory Project

General
John's Hopkins Breast Cancer Center
American Cancer Society - Learn About Breast Cancer Page
History of breast cancer treatment
The Breast: Neoplasms of the Breast
Breast Cancer Care (UK charity)
Abortion and Breast Cancer
National Cancer Institute: Breast Cancer
Breast Cancer Campaign (UK research charity)
Imaginis -Award winning Breast Cancer site

Research and statistics
Breast cancer incidence by country
eMaxHealth Breast Cancer Publishes Research News on Breast Cancer from Research Institutions and Universities

Clinical

RadiologyInfo - The radiology information resource for patients: Breast Cancer
Surgery Choices for Women with Early-Stage Breast Cancer, National Cancer Institute
Mastectomy vs.n Lumpectomy: Who Decides?, National Research Center for Women & Families
Australia: Cancer Control Bulletin Alcohol and cancer risk
Cornell University Alcohol and the Risk of Breast Cancer

Videos

Other

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Pancreatic Cancer

2007-09-04T13:15:00.000-07:00

November is Pancreatic Cancer Awareness month. A purple ribbon is worn in rememberance of those who have struggled, or are struggling with pancreatic cancer.

Pancreatic cancer
From Wikipedia, the free encyclopedia

Pancreatic cancer
Classification & external resources

ICD-10
C 25.
ICD-9
157
OMIM
260350
DiseasesDB
9510
MedlinePlus
000236
eMedicine
med/1712
MeSH
D010190

Pancreatic cancer is a malignant tumour within the pancreatic gland. Each year about 33,000 individuals in the United States are diagnosed with this condition, and more than 60,000 in Europe. Depending on the extent of the tumor at the time of diagnosis, the prognosis is generally regarded as poor, with few victims still alive 5 years after diagnosis, and complete remission still extremely rare.[1]

About 95 percent of pancreatic tumors are adenocarcinomas (M 8140/3). The remaining 5 percent include other tumors of the exocrine pancreas (e.g. serous cystadenomas), acinar cell cancers, and pancreatic neuroendocrine tumors (such as insulinomas, M 8150/1, M 8150/3). These tumors have a completely different diagnostic and therapeutic profile, and generally a more favorable prognosis.[1]

Signs and symptoms

Presentation
Early diagnosis of pancreatic cancer is difficult because the symptoms are so non-specific and varied.

Common symptoms include pain in the upper abdomen that typically radiates to the back and is relieved by leaning forward (seen in carcinoma of the body or tail of the pancreas),
loss of appetite,
significant weight loss and
painless jaundice related to bile duct obstruction (carcinoma of the head of the pancreas). All of these symptoms can have multiple other causes. Therefore, pancreatic cancer is often not diagnosed until it is advanced.

Jaundice occurs when the tumor grows and obstructs the common bile duct, which
runs partially through the head of the pancreas. Tumours of the head of the
pancreas (approximately 60% of cases) are more likely to cause jaundice by this
mechanism.
Trousseau's sign, in which blood clots form spontaneously in the portal blood
vessels, the deep veins of the extremities, or the superficial veins anywhere on the body, is sometimes associated with pancreatic cancer.
Clinical depression
has been reported in association with pancreatic cancer, sometimes presenting
before the cancer is diagnosed. However, the mechanism for this association is
not known.[2].

Predisposing factors
Risk factors for pancreatic cancer include:[3]

Age
Male gender
African ethnicity
Smoking
Diets high in meat
Obesity
Diabetes
Chronic pancreatitis has been linked, but is not known to be causal.
Occupational exposure to certain pesticides, dyes, and chemicals related to gasoline
Family history
Helicobacter pylori infection
Gingivitis or periodontal disease.[4]

Diagnosis

Courvoisier's law defines the presence of jaundice and a painlessly distended gallbladder as strongly indicative of pancreatic cancer, and may be used to distinguish pancreatic cancer from gallstones.
Pancreatic cancer is usually discovered during the course of the evaluation of aforementioned symptoms.
Liver function tests may show a combination of results indicative of bile duct obstruction (raised conjugated bilirubin, γ-glutamyl transpeptidase and alkaline phosphatase levels). CA19-9 (carbohydrate antigen 19.9) is a tumor marker that is frequently elevated in pancreatic cancer.
Imaging studies, such as ultrasound or abdominal CT may be used to identify tumors. Endoscopic ultrasound (EUS) is another procedure that can help visualize the tumor and obtain tissue to establish the diagnosis.
Recent research indicates that in pancreatic cancer malignancies, the tumor contains markedly higher levels of certain microRNAs (miRNA) than does the patient's benign pancreatic tissue or that found in other healthy pancreases. [citation needed] This paves the way for two possibilities:

1) a more early but likely expensive genetic and biochemical molecular screening test profile, which would be an innovation in this cancer; and
2) also possible new, creative and more effective therapies based on the various microRNA levels. This opens an exciting new front in confronting a very deadly disease.

Treatment
Treatment of pancreatic cancer depends on the stage of the cancer.[5]

Recent advances have made resection (surgical removal) of tumors that were previously unresectable due to blood vessel involvement possible.
The Whipple procedure is the most common surgical treatment for cancers involving the head of the pancreas.
Fluorouracil, gemcitabine, and erlotinib are the chemotherapeutic drug agents of choice. Gemcitabine was approved by the US FDA in 1998 after a clinical trial reported improvements in quality of life in patients with advanced prostate cancer. This marked the first FDA approval of a chemotherapy drug for a non-survival clinical trial endpoint.
On the back of the results of a Canadian led Phase III Randomised Controlled trial involving 569 patients with advanced pancreatic cancer, the US FDA has licensed the use of erlotinib (Tarceva) in combination with gemcitabine as a palliative agent for this tumour. This trial compared the action of gemcitabine/erlotinib vs gemcitabine/placebo and demonstrated improved survival rates, improved tumour response and improved progression free survival rates. The survival improvement with the combination is on the order of less than four weeks, leading some cancer experts to question the incremental value of adding erlotinib to gemcitabine treatment. New trials are now investigating the effect of the above combination in the adjuvant and neoadjuvant setting.[6]
In September 2006, it was announced that a new vaccine had been developed to fight pancreatic cancer, with testing on human patients showing promising results.[7][8]

Prognosis
Patients diagnosed with pancreatic cancer typically have a poor prognosis partly because the cancer usually causes no symptoms early on, leading to metastatic disease at time of diagnosis. Median survival from diagnosis is around 3 to 6 months; 5-year survival is much less than 5%[9] With 32,180 new diagnoses in the United States every year, and 31,800 deaths, mortality approaches 99%, giving pancreatic cancer the highest fatality rate of all cancers and the fourth highest cancer killer in the United States amongst both men and women.[10]

Pancreatic cancer occasionally may result in diabetes. Insulin production is hampered and it has been suggested that the cancer can also prompt the onset of diabetes and vice versa.[11]

Prevention
Prevention of pancreatic cancer consists of avoiding risk factors when possible[12] Cigarette smoking is considered to be the most significant and avoidable risk factor for pancreatic cancer. Maintaining a healthy weight and exercising may be helpful. Additionally, increasing consumption of fruits, vegetables, and whole grains while decreasing red meat intake is recommended by the American Cancer Society.

The relationship of overall fruit and vegetable consumption with pancreatic cancer has been questioned by several research groups.[13][14] In 2006 a large prospective cohort study of over 80,000 subjects failed to prove a definite association.[15] The evidence in support of this lies mostly in small case-control studies.

In September 2006, a long-term study concluded that taking Vitamin D can substantially cut the risk of pancreatic cancer (as well as other cancers) by up to 50%.[16][17][18] More studies of this have been called for.

Several studies, including one published June 1, 2007, indicate that B vitamins such as B12, B6, and folate, can reduce the risk of pancreatic cancer when consumed in food, but not when ingested in vitamin tablet form.[19][20]

Awareness
November is Pancreatic Cancer Awareness Month
Purple is the traditional color chosen to represent pancreatic cancer

An estimated 52.7 million dollars was spent on pancreatic cancer research in 2004 of the National Cancer Institute’s (NCI) cancer research budget. This is just 1% of the NCI’s 4.824 billion dollar cancer research budget for 2004.[21]

Despite the especially lethal nature of pancreatic cancer, the research spending per pancreatic cancer patient is only $1145, the lowest of any leading cancer.[22]

For a list of celebrities who have succumbed to this disease, see Category:Pancreatic cancer deaths

The Pancreatic Cancer Action Network (PanCAN) was created as an advocacy group for pancreatic cancer.

The national charity Pancreatic Cancer UK works to raise awareness in the UK

External links

Pancreatic Cancer Action Network (PanCAN)
The Pancreatic Society of Great Britain and Ireland
The Johns Hopkins Pancreatic Cancer Web Site
Rare Pancreatic & Neuroendocrine Cancer Support
Pancreatic Cancer UK
Confronting Pancreatic Cancer (Pancreatica.org)
Cancer of the Pancreas (Cancer Supportive Care Program)
American Cancer Society: Detailed Guide on Pancreatic Cancer
The National Familial Pancreas Tumor Registry
Pancreatic Cancer Collaborative Registry (PCCR)

References
^ a b Ghaneh P, Costello E, Neoptolemos JP (2007). "Biology and management of pancreatic cancer". Gut 56 (8): 1134-52. DOI:10.1136/gut.2006.103333. PMID 17625148.
^ Carney CP, Jones L, Woolson RF, Noyes R Jr, Doebbeling BN. Relationship between depression and pancreatic cancer in the general population. Psychosom Med 2003;65:884-8. PMID 14508036.
^ http://www.cancer.org/docroot/CRI/content/CRI_2_4_2X_What_are_the_risk_factors_for_pancreatic_cancer_34.asp?sitearea=
^ Michaud DS, Joshipura K, Giovannucci E, Fuchs CS (2007). "A prospective study of periodontal disease and pancreatic cancer in US male health professionals". J. Natl. Cancer Inst. 99 (2): 171-5. DOI:10.1093/jnci/djk021. PMID 17228001.
^ http://www.cancersupportivecare.com/pancreas.html#stage
^ FDA approval briefing
^ http://abclocal.go.com/kgo/story?section=edell&id=4605575
^ http://abclocal.go.com/kgo/story?section=edell&id=4605594
^ http://www.who.int/tobacco/research/cancer/en/
^ http://pancan.org/About/pancreaticCancerStats.html
^ http://www.molecular-cancer.com/content/2/1/4
^ http://www.cancer.org/docroot/CRI/content/CRI_2_4_2X_Can_pancreatic_cancer_be_prevented_34.asp?rnav=cri
^ Coughlin, SS; Calle EE, Patel AV, Thun MJ. (2000 Dec). "Predictors of pancreatic cancer mortality among a large cohort of United States adults.". Cancer Causes Control. 11 (10): 915-23.. PMID 11142526. Retrieved on 2007-02-27.
^ Zheng, W; et al (1993 Sep). "A cohort study of smoking, alcohol consumption, and dietary factors for pancreatic cancer (United States).". Cancer Causes Control. 4 (5): 477-82.. PMID 8218880. Retrieved on 2007-02-27.
^ Larsson, Susanna; Niclas Håkansson, Ingmar Näslund, Leif Bergkvist and Alicja Wolk (February 2006). "Fruit and vegetable consumption in relation to pancreatic cancer risk: a prospective study.". Cancer Epidemiology Biomarkers & Prevention 15: 301-305. PMID 16492919. Retrieved on 2007-02-27.
^ http://news.bbc.co.uk/1/hi/health/5334534.stm
^ http://www.webmd.com/content/article/127/116673.htm
^ http://www.forbes.com/forbeslife/health/feeds/hscout/2006/09/14/hscout534925.html
^ Plasma Folate, Vitamin B6, Vitamin B12, and Homocysteine and Pancreatic Cancer Risk in Four Large Cohorts -- Schernhammer et al. 67 (11): 5553 -- Cancer Research. Retrieved on 2007-06-04.
^ United Press International - Consumer Health Daily - Briefing. Retrieved on 2007-06-04.
^ http://pancan.org/About/pancreaticCancerStats.html
^ http://pancan.org/About/pancreaticCancerStats.html

v • d • e Pathology: Tumors, neoplasia, and oncology (C00-D48, 140-239)
Benign tumors
Hyperplasia - Cyst - Pseudocyst - Hamartoma - Benign neoplasm
Malignant progression
Dysplasia - Carcinoma in situ - Invasive cancer - Metastasis
Topography
Anus - Bladder - Bile duct - Bone - Brain - Breast - Cervix - Colon/rectum - Endometrium - Esophagus - Eye - Gallbladder - Head/Neck - Liver - Kidney - Larynx - Lung - Mediastinum (chest) - Mouth - Ovaries - Pancreas - Penis - Prostate - Skin - Small intestine - Stomach - Tailbone - Testicles - Thyroid
Misc.
Tumor suppressor genes/oncogenes - Staging/grading - Carcinogenesis - Carcinogen - Research - Paraneoplastic phenomenon - List of oncology-related terms
Retrieved from "http://en.wikipedia.org/wiki/Pancreatic_cancer"

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