About eleven children die from cancer daily in the US.
The National Cancer Institute (NCI) is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S. National Cancer Program and conducts and supports research, training, health information dissemination, and other activities related to the causes, prevention, diagnosis, and treatment of cancer; the supportive care of cancer patients and their families; and cancer survivorship. As of July 2010, the current director of the NCI is Dr. Harold Varmus.
The National Cancer Institute mediates the majority of its mission via an extramural program that provides grants for cancer research. Additionally, the National Cancer Institute has intramural research programs, which constitutes a small fraction of the overall National Cancer Institute budget, in Bethesda, Maryland and at the Frederick National Laboratory for Cancer Research at Fort Detrick, in Frederick, Maryland.
Congress established the NCI by the National Cancer Institute Act, August 6, 1937, as an independent research institute. Congress then made the NCI an operating division of the National Institutes of Health by the Public Health Service Act, July 1, 1944. Congress amended the Public Health Service Act with the National Cancer Act of 1971 to broaden the scope and responsibilities of the NCI "in order more effectively to carry out the national effort against cancer." Over the years, legislative amendments have maintained the NCI authorities and responsibilities and added new information dissemination mandates as well as a requirement to assess the incorporation of state-of-the-art cancer treatments into clinical practice.
The NCI played an early role in the discovery of anti-cancer drugs in the U.S. According to a 1996 NCI analysis of drugs approved by the FDA, two-thirds of the anti-cancer drugs approved as of the end of 1995 were NCI-sponsored Investigational New Drugs:][
Hormones and steroids
In addition, scientists in the NCI played an important role in the discovery and development of important AIDS drugs including zidovudine (AZT), didanosine (ddI), and zalcitabine (ddC).
On March 12, 2013 the NCI reported that cannabis “inhibited the survival of both estrogen receptor–positive and estrogen receptor–negative breast cancer cell lines.” The NCI report also examined whether patients who smoke marijuana rather than ingesting it orally are exposed to a higher risk of lung and certain digestive system cancers. According to the government, 19 studies “failed to demonstrate statistically significant associations between marijuana inhalation and lung cancer.” The same report showed marijuana slows or stops the growth of certain lung cancer cells and suggested that marijuana may provide “risk reduction and treatment of colorectal cancer.” In its report, the National Cancer Institute also identified a “study of intratumoral injection of delta-9-THC in patients with recurrent glioblastoma” that showed tumor reduction in the test participants.
The evolution of strategies at the National Cancer Institute (NCI) illustrates the changes in screening that have resulted from advances in cancer biology. The Developmental Therapeutics Program (DTP) operates a tiered anti-cancer compound screening program with the goal of identifying novel chemical leads and biological mechanisms. The DTP screen is a three phase screen which includes: an initial screen which first involves a single dose cytotoxicity screen with the 60 cell line assay. Those passing certain thresholds are subjected to a 5 dose screen of the same 60 cell-line panel to determine a more detailed picture of the biological activity. A second phase screen establishes the Maximum Tolerable Dosage and involves in vivo examination of tumor regression using the Hollow fiber assay. The third phase of the study is the human tumor xenograft evaluation. Active compounds are selected for testing based on several criteria: disease type specificity in the in vitro assay, unique structure, potency, and demonstration of a unique pattern of cellular cytotoxicity or cytostasis, indicating a unique mechanism of action or intracellular target. Some of the approved cancer treatment drugs developed with DTP involvement are: Fluorouracil (1962, NSC-19893), Bleomycin (1973, NSC-125066), Doxorubicin (1974, NSC-123127), cis-Platinum (1978, NSC-119875), Carboplatin (1989, NSC-241240), Taxol (1992, NSC-192573) and Erbitux (2004, NSC-632307). Drug testing data are represented as a mean graph that displays growth inhibition in a standard bar graph representation. The mean graph is constructed by projecting bars to the right or left of the mean, depending on whether an individual cell line is more or less sensitive than the average line in the panel. Further the length of each bar is proportional to the relative sensitivity of the cell lines. Thus, each agent can be represented by a characteristic fingerprint of cell-line responsiveness, indicated by the bar graph presentation. These data are presented and analyzed in this section. The broad screen provides a basis for comparison with other compounds, many of which have a known mechanism of action. The NCI COMPARE program is an online database and comparison tool which analyzes both one-dose and five-dose data cytotoxicity data for the 60 cell line panel for similar activity profiles with all the compounds screened previously by the DTP. A compound is entered into the program as a seed, and the computer database elicits a list of those agents that have similar patterns of cellular cytotoxicity. A correlation coefficient is also expressed relating the closeness of the seed to those agents listed by the computer program. Close correlations between agents demonstrates biological and pharmacological importance and implies a common intracellular target despite dissimilarity in structure. A high correlation of cytotoxicity with compounds of known biological mechanism is often predictive of the drugs mechanism of action and thus a tool to aid in the drug development and testing. It also tells if there is any unique response of the drug which is not similar to any of the standard prototype compounds in the NCI database.
Methodology of the in-vitro Cancer Screen The protocol for the NCI-60 screen is as follows. The human tumor cell lines are grown in RPMI 1640 medium containing 5% fetal bovine serum and 2 mM L-glutamine. For a typical screening experiment, cells are inoculated into 96 well microtiter plates in 100 µL at plating densities ranging from 5,000 to 40,000 cells/well depending on the doubling time of individual cell lines. After cell inoculation, the microtiter plates are incubated at 37°C, 5% CO2, 95% air and 100% relative humidity for 24 h prior to addition of experimental drugs. After 24 h, two plates of each cell line are fixed in situ with TCA, to represent a measurement of the cell population for each cell line at the time of drug addition (Tz). Experimental drugs are solubilized in dimethyl sulfoxide at 400-fold the desired final maximum test concentration and stored frozen prior to use. At the time of drug addition, an aliquot of frozen concentrate is thawed and diluted to twice the desired final maximum test concentration with complete medium containing 50 µg/mL gentamicin. Additional four, 10-fold or ½log serial dilutions are made to provide a total of five drug concentrations plus control. Aliquots of 100 µl of these different drug dilutions are added to the appropriate microtiter wells already containing 100 µl of medium, resulting in the required final drug concentrations. Following drug addition, the plates are incubated for an additional 48 h at 37°C, 5% CO2, 95% air, and 100% relative humidity. For adherent cells, the assay is terminated by the addition of cold TCA. Cells are fixed in situ by the gentle addition of 50 µl of cold 50% (w/v) TCA (final concentration, 10% TCA) and incubated for 60 minutes at 4°C. The supernatant is discarded, and the plates are washed five times with tap water and air dried. Sulforhodamine B (SRB) solution (100 µl) at 0.4% (w/v) in 1% acetic acid is added to each well, and plates are incubated for 10 minutes at room temperature. After staining, unbound dye is removed by washing five times with 1% acetic acid and the plates are air dried. Bound stain is subsequently solubilized with 10 mM trizma base, and the absorbance is read on an automated plate reader at a wavelength of 515 nm. For suspension cells, the methodology is the same except that the assay is terminated by fixing settled cells at the bottom of the wells by gently adding 50 µl of 80% TCA (final concentration, 16% TCA). Using the seven absorbance measurements [time zero, (Tz), control growth, (C), and test growth in the presence of drug at the five concentration levels (Ti)], the percentage growth is calculated at each of the drug concentrations levels. Percentage growth inhibition is calculated as: [(Ti-Tz)/(C-Tz)] x 100 for concentrations for which Ti>/=Tz [(Ti-Tz)/Tz] x 100 for concentrations for which Ti<Tz. Three dose response parameters are calculated for each experimental agent. 1) GI50 Growth inhibition of 50% (GI50) is calculated from [(Ti-Tz)/(C-Tz)] x 100 = 50, which is the drug concentration resulting in a 50% reduction in the net protein increase (as measured by SRB staining) in control cells during the drug incubation. 2) TGI The drug concentration resulting in total growth inhibition (TGI) is calculated from Ti = Tz. 3) LC50 The LC50 (concentration of drug resulting in a 50% reduction in the measured protein at the end of the drug treatment as compared to that at the beginning) indicating a net loss of cells following treatment is calculated from [(Ti-Tz)/Tz] x 100 = -50. Values are calculated for each of these three parameters if the level of activity is reached; however, if the effect is not reached or is exceeded, the value for that parameter is expressed as greater or less than the maximum or minimum concentration tested.
The NCI provides funding for numerous cancer research endeavors. Two of its largest known grants include the Radiological Physics Center (RPC) in Houston, Texas and the Quality Assurance Review Center (QARC) in Providence, Rhode Island. The RPC assures the NCI of proper participation in the physics-related aspects of its studies and QARC provides radiotherapy quality assurance and diagnostic imaging data management to all of the NCI sponsored cooperative groups. The RPC essentially guides all participating institutions as to how radiation is to be applied in a radiotherapy protocol. QARC on the other hand performs thousands of radiotherapy reviews per year and receives radiotherapy data from around 1,000 hospitals in both the United States and abroad. In all, over 30,000 cases have been reviewed at QARC since its inception in 1977. QARC also maintains a strategic affiliation with the University of Massachusetts Medical School in Worcester, Massachusetts. The RPC has been consistently funded by the NCI since 1968, and QARC has received support from the NCI since 1980.
The NCI has set up a network of 12 Physical Sciences-Oncology Centers (PS-OCs) linking the physical sciences to the study of cancer.
Colorectal cancer, commonly known as colon cancer or bowel cancer, is a cancer from uncontrolled cell growth in the colon or rectum (parts of the large intestine), or in the appendix. Genetic analysis shows that essentially colon and rectal tumours are genetically the same cancer. Symptoms of colorectal cancer typically include rectal bleeding and anemia which are sometimes associated with weight loss and changes in bowel habits.
Most colorectal cancer occurs due to lifestyle and increasing age with only a minority of cases associated with underlying genetic disorders. It typically starts in the lining of the bowel and if left untreated, can grow into the muscle layers underneath, and then through the bowel wall. Screening is effective at decreasing the chance of dying from colorectal cancer and is recommended starting at the age of 50 and continuing until a person is 75 years old. Localized bowel cancer is usually diagnosed through sigmoidoscopy or colonoscopy.
Cancers that are confined within the wall of the colon are often curable with surgery while cancer that has spread widely around the body is usually not curable and management then focuses on extending the person's life via chemotherapy and improving quality of life. Colorectal cancer is the third most commonly diagnosed cancer in the world, but it is more common in developed countries. Around 60% of cases were diagnosed in the developed world. It is estimated that worldwide, in 2008, 1.23 million new cases of colorectal cancer were clinically diagnosed, and that it killed 608,000 people.
The symptoms and signs of colorectal cancer depend on the location of tumor in the bowel, and whether it has spread elsewhere in the body (metastasis). The classic warning signs include: worsening constipation, blood in the stool, decrease in stool calibre, loss of appetite, loss of weight, and nausea or vomiting in someone over 50 years old. While rectal bleeding or anemia are high-risk features in those over the age of 50, other commonly-described symptoms including weight loss and change in bowel habit are typically only concerning if associated with bleeding.
Greater than 75-95% of colon cancer occurs in people with little or no genetic risk. Other risk factors include older age, male gender, high intake of fat, alcohol or red meat, obesity, smoking and a lack of physical exercise. Approximately 10% of cases are linked to insufficient activity. The risk for alcohol appears to increase at greater than one drink per day.
People with inflammatory bowel disease (ulcerative colitis and Crohn's disease) are at increased risk of colon cancer. The risk is greater the longer a person has had the disease, and the worse the severity of inflammation. In these high risk groups both prevention with aspirin and regular colonoscopies are recommended. People with inflammatory bowel disease account for less than 2% of colon cancer cases yearly. In those with Crohn's disease 2% get colorectal cancer after 10 years, 8% after 20 years, and 18% after 30 years. In those with ulcerative colitis approximately 16% develop either a cancer precursor or cancer of the colon over 30 years.
Those with a family history in two or more first-degree relatives have a two to threefold greater risk of disease and this group accounts for about 20% of all cases. A number of genetic syndromes are also associated with higher rates of colorectal cancer. The most common of these is hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome) which is present in about 3% of people with colorectal cancer. Other syndromes that are strongly associated include: Gardner syndrome, and familial adenomatous polyposis (FAP) in which cancer nearly always occurs and is the cause of 1% of cases.
Most deaths due to colon cancer are associated with metastatic disease. A gene that appears to contribute to the potential for metastatic disease - metastasis-associated in colon cancer-1 - has been isolated. It is a transcriptional factor that influences the expression of hepatocyte growth factor. This gene is associated with the proliferation, invasion and scattering of colon cancer cells in cell culture and tumor growth and metastasis in mice. It has also been associated with the response to treatment.
Epigenetic alterations are much more frequent in colon cancer than genetic (mutational) alterations. As described by Vogelstein et al., an average cancer of the colon has only 1 or 2 oncogene mutations and 1 to 5 tumor suppressor mutations (together designated “driver mutations”), with about 60 further “passenger” mutations. The oncogenes and tumor suppressor genes are well studied and are described below under Pathogenesis.
However, by comparison, epigenetic alterations in colon cancers are frequent and affect hundreds of genes. For instance, there are types of small RNAs called microRNAs that are about 22 nucleotides long. These microRNAs (or miRNAs) do not code for proteins, but they can “target” protein coding genes and reduce their expression. Expression of these miRNAs can be epigenetically altered. As one example, the epigenetic alteration consisting of CpG island methylation of the DNA sequence encoding miR-137 reduces its expression, and this is a frequent early epigenetic event in colorectal carcinogenesis, occurring in 81% of colon cancers and in 14% of the normal appearing colonic mucosa adjacent to the cancers. The altered adjacent tissues associated with these cancers are called field defects. Silencing of miR-137 can affect expression of about 500 genes, the targets of this miRNA. Changes in the level of miR-137 expression result in changed mRNA expression of the target genes by 2 to 20-fold and corresponding, though often smaller, changes in expression of the protein products of the genes. Other microRNAs, with likely comparable numbers of target genes, are even more frequently epigenetically altered in colonic field defects and in the colon cancers that arise from them. These include miR-124a, miR-34b/c and miR-342 which are silenced by CpG island methylation of their encoding DNA sequences in primary tumors at rates of 99%, 93% and 86%, respectively, and in the adjacent normal appearing mucosa at rates of 59%, 26% and 56%, respectively.
In addition to epigenetic alteration of expression of miRNAs, other common types of epigenetic alterations in cancers that change gene expression levels include direct hypermethylation or hypomethlyation of CpG islands of protein-encoding genes and alterations in histones and chromosomal architecture that influence gene expression. As an example, 147 hypermethylations and 27 hypomethylations of protein coding genes were frequently associated with colorectal cancers. Of the hypermethylated genes, 10 were hypermethylated in 100% of colon cancers, and many others were hypermethylated in more than 50% of colon cancers. In addition, 11 hypermethylations and 96 hypomethyaltions of miRNAs were also associated with colorectal cancers.
Recent evidence indicates that early epigenetic reductions of DNA repair enzyme expression likely lead to the genomic and epigenomic instability characteristic of cancer.
As summarized in the articles Carcinogenesis and Neoplasm, for sporadic cancers in general, a deficiency in DNA repair is occasionally due to a mutation in a DNA repair gene, but is much more frequently due to epigenetic alterations that reduce or silence expression of DNA repair genes.
Colorectal cancer is a disease originating from the epithelial cells lining the colon or rectum of the gastrointestinal tract, most frequently as a result of mutations in the Wnt signaling pathway that artificially increase signaling activity. The mutations can be inherited or are acquired, and most probably occur in the intestinal crypt stem cell.][ The most commonly mutated gene in all colorectal cancer is the APC gene, which produces the APC protein. The APC protein is a "brake" on the accumulation of β-catenin protein; without APC, β-catenin accumulates to high levels and translocates (moves) into the nucleus, binds to DNA, and activates the transcription of genes that are normally important for stem cell renewal and differentiation but when inappropriately expressed at high levels can cause cancer. While APC is mutated in most colon cancers, some cancers have increased β-catenin because of mutations in β-catenin (CTNNB1) that block its degradation, or they have mutation(s) in other genes with function analogous to APC such as AXIN1, AXIN2, TCF7L2, or NKD1.
Beyond the defects in the Wnt-APC-beta-catenin signaling pathway, other mutations must occur for the cell to become cancerous. The p53 protein, produced by the TP53 gene, normally monitors cell division and kills cells if they have Wnt pathway defects. Eventually, a cell line acquires a mutation in the TP53 gene and transforms the tissue from an adenoma into an invasive carcinoma. (Sometimes the gene encoding p53 is not mutated, but another protective protein named BAX is.)
Other apoptotic proteins commonly deactivated in colorectal cancers are TGF-β and DCC (Deleted in Colorectal Cancer). TGF-β has a deactivating mutation in at least half of colorectal cancers. Sometimes TGF-β is not deactivated, but a downstream protein named SMAD is. DCC commonly has deletion of its chromosome segment in colorectal cancer.
Some genes are oncogenes - they are overexpressed in colorectal cancer. For example, genes encoding the proteins KRAS, RAF, and PI3K, which normally stimulate the cell to divide in response to growth factors, can acquire mutations that result in over-activation of cell proliferation. The chronological order of mutations is sometimes important, with a primary KRAS mutation generally leading to a self-limiting hyperplastic or borderline lesion, but if occurring after a previous APC mutation it often progresses to cancer. PTEN, a tumor suppressor, normally inhibits PI3K, but can sometimes become mutated and deactivated.
Comprehensive, genome-scale analysis has revealed that colorectal carcinomas are clearly separable into hypermutated and non-hypermutated tumor types. In addition to the oncogenic and inactivating mutations described for the genes above, non-hypermutated samples also contain mutated CTNNB1, FAM123B, SOX9, ATM, and ARID1A. Progressing through a distinct set of genetic events, hypermutated tumors display mutated forms of ACVR2A, TGFBR2, MSH3, MSH6, SLC9A9, TCF7L2, and BRAF. The common theme among these genes, across both tumor types, is their involvement in WNT and TGF-β signaling pathways, which in turn results in increased activity of MYC, a central player in colorectal cancer.
The term “field cancerization” was first used in 1953 to describe an area or “field” of epithelium that has been preconditioned by (at that time) largely unknown processes so as to predispose it towards development of cancer. Since then, the terms “field cancerization” and “field defect” have been used to describe pre-malignant tissue in which new cancers are likely to arise.
Field defects are important in progression to colon cancer.
However, in most cancer research, as pointed out by Rubin “The vast majority of studies in cancer research has been done on well-defined tumors in vivo, or on discrete neoplastic foci in vitro. Yet there is evidence that more than 80% of the somatic mutations found in mutator phenotype human colorectal tumors occur before the onset of terminal clonal expansion…” Similarly, Vogelstein et al. point out that more than half of somatic mutations identified in tumors occurred in a pre-neoplastic phase (in a field defect), during growth of apparently normal cells. Likewise, epigenetic alterations present in tumors may have occurred in pre-neoplastic field defects.
Diagnosis of colorectal cancer is via tumor biopsy typically done during colonoscopy or sigmoidoscopy, depending on the location of the lesion. The extent of the disease is then usually determined by a CT scan of the chest, abdomen and pelvis. There are other potential imaging test such as PET and MRI which may be used in certain cases. Colon cancer staging is done next and based on the TNM system which is determined by how much the initial tumor has spread, if and where lymph nodes are involved, and if and how many metastases there are.
The histology of the tumor is usually reported from the analysis of tissue taken from a biopsy or surgery. A pathology report will usually contain a description of cell type and grade. The most common colon cancer cell type is adenocarcinoma which accounts for 95% of cases. Other, rarer types include lymphoma and squamous cell carcinoma.
Cancers on the right side (ascending colon and cecum) tend to be exophytic, that is, the tumour grows outwards from one location in the bowel wall. This very rarely causes obstruction of feces, and presents with symptoms such as anemia. Left-sided tumours tend to be circumferential, and can obstruct the bowel much like a napkin ring which can present with thinner calibre stools.
Adenocarcinoma is a malignant epithelial tumor, originating from glandular epithelium of the colorectal mucosa. It invades the wall, infiltrating the muscularis mucosae, the submucosa and thence the muscularis propria. Tumor cells describe irregular tubular structures, harboring pluristratification, multiple lumens, reduced stroma ("back to back" aspect). Sometimes, tumor cells are discohesive and secrete mucus, which invades the interstitium producing large pools of mucus/colloid (optically "empty" spaces) - mucinous (colloid) adenocarcinoma, poorly differentiated. If the mucus remains inside the tumor cell, it pushes the nucleus at the periphery - "signet-ring cell." Depending on glandular architecture, cellular pleomorphism, and mucosecretion of the predominant pattern, adenocarcinoma may present three degrees of differentiation: well, moderately, and poorly differentiated.
Most colorectal cancer tumors are thought to be cyclooxygenase-2 (COX-2) positive.][ This enzyme is generally not found in healthy colon tissue, but is thought to fuel abnormal cell growth.
Appearance of the inside of the colon showing one invasive colorectal carcinoma (the crater-like, reddish, irregularly shaped tumor).
Gross appearance of a colectomy specimen containing two adenomatous polyps (the brownish oval tumors above the labels, attached to the normal beige lining by a stalk) and one invasive colorectal carcinoma (the crater-like, reddish, irregularly shaped tumor located above the label).
Endoscopic image of colon cancer identified in sigmoid colon on screening colonoscopy in the setting of Crohn's disease.
PET/CT of a staging exam of colon carcinoma. Besides the primary tumor a lot of lesions can be seen. On cursor position: lung nodule.
Micrographs (H&E stain)
Cancer — Invasive adenocarcinoma (the most common type of colorectal cancer). The cancerous cells are seen in the center and at the bottom right of the image (blue). Near normal colon-lining cells are seen at the top right of the image.
Cancer — Histopathologic image of colonic carcinoid.
Precancer — Tubular adenoma (left of image), a type of colonic polyp and a precursor of colorectal cancer. Normal colorectal mucosa is seen on the right.
Precancer — Colorectal villous adenoma.
Most colorectal cancers should be preventable, through increased surveillance and improved lifestyle.][.
Current dietary recommendations to prevent colorectal cancer include increasing the consumption of whole grains, fruits and vegetables, and reducing the intake of red meat. The evidence for fiber and fruits and vegetables however is poor. Physical activity can moderately reduce the risk of colorectal cancer.
Aspirin and celecoxib appear to decrease the risk of colorectal cancer in those at high risk. However it is not recommended in those at average risk. There is tentative evidence for calcium supplementation but it is not sufficient to make a recommendation. Vitamin D intake and blood levels are associated with a lower risk of colon cancer.
More than 80% of colorectal cancers arise from adenomatous polyps making this cancer amenable to screening. Diagnosis of cases of colorectal cancer through screening tends to occur 2–3 years before diagnosis of cases with symptoms. Screening has the potential to reduce colorectal cancer deaths by 60%.
The three main screening tests are fecal occult blood testing, flexible sigmoidoscopy and colonoscopy. Of the three, only sigmoidoscopy cannot screen the right side of the colon where 42% of malignancies are found. Virtual colonoscopy via a CT scan appears as good as standard colonoscopy for detecting cancers and large adenomas but is expensive, associated with radiation exposure, and cannot remove any detected abnormal growths like standard colonoscopy can.
A new screening method is the M2-PK Test. The enzyme biomarker M2-PK has been identified as a key enzyme in colorectal cancers and polyps. M2-PK does not depend on blood in the stool and is specifically related to changes in the tumour metabolism. It does not require any special preparation prior to testing. Only a small stool sample is needed. M2-PK features a high sensitivity for colorectal cancer and polyps and is able to detect bleeding and non-bleeding colorectal cancer and polyps. In the event of a positive result people would be asked to undergo further examination e.g. colonoscopy.
Fecal occult blood testing of the stool is typically recommended every two years and can be either guaiac based or immunochemical. Medical societies recommend screening between the age of 50 and 75 years with sigmoidoscopy every 5 years and colonoscopy every 10 years. For those at high risk, screenings usually begin at around 40. For people with average risk who have had a high-quality colonoscopy with normal results, the American Gastroenterological Association does not recommend any type of screening in the 10 years following the colonoscopy. For people over 75 or those with a life expectancy of less than 10 years, screening is not recommended.
The treatment of colorectal cancer can be aimed at curation or palliation. The decision on which aim to adopt depends on various factors, including the patient's health and preferences, as well as the stage of the tumour. When colorectal cancer is caught early, surgery can be curative. However, when it is detected at later stages for which (metastases are present), this is less likely and treatment is often directed at palliation, to relieve symptoms caused by the tumour and keep the person as comfortable as possible.
For people with localized cancer, the preferred treatment is complete surgical removal with adequate margins, with the attempt of achieving a cure. This can either be done by an open laparotomy or sometimes laparoscopically. If there are only a few metastases in the liver or lungs they may also be removed. Sometimes chemotherapy is used before surgery to shrink the cancer before attempting to remove it. The two most common sites of recurrence of colorectal cancer is in the liver and lungs.
In both cancer of the colon and rectum, chemotherapy may be used in addition to surgery in certain cases as adjuvant therapy. In rectal cancer alone, chemotherapy may be used in the neoadjuvant setting.
If cancer has entered the lymph nodes, adding the chemotherapy agents fluorouracil or capecitabine increases life expectancy. If the lymph nodes do not contain cancer, the benefits of chemotherapy are controversial. If the cancer is widely metastatic or unresectable, treatment is then palliative. Typically in this case, a couple of different chemotherapy medications are used. Chemotherapy drugs may include combinations of agents including fluorouracil, capecitabine, UFT, leucovorin, irinotecan, or oxaliplatin.
While a combination of radiation and chemotherapy may be useful for rectal cancer, its use in colon cancer is not routine due to the sensitivity of the bowels to radiation. Just as for chemotherapy, radiotherapy can be used in the neoadjuvant and adjuvant setting for some stages of rectal cancer.
In people with incurable colorectal cancer, palliative care can be considered for improving quality of life. Surgical options may include non-curative surgical removal of some of the cancer tissue, bypassing part of the intestines, or stent placement. These procedures can be considered to improve symptoms and reduce complications such as bleeding from the tumor, abdominal pain and intestinal obstruction. Non-operative methods of symptomatic treatment include radiation therapy to decrease tumor size as well as pain medications.
In Europe the five-year survival for colorectal cancer is less than 60%. In the developed world about a third of people who get the disease die from it.
Survival is directly related to detection and the type of cancer involved, but overall is poor for symptomatic cancers, as they are typically quite advanced. Survival rates for early stage detection is about 5 times that of late stage cancers. For example, patients with a tumor that has not breached the muscularis mucosa (TNM stage Tis, N0, M0) have an average 5-year survival of 100%, while those with an invasive cancer, i.e. T1 (within the submucosal layer) or T2 (within the muscular layer) cancer have an average 5-year survival of approximately 90%. Those with a more invasive tumor, yet without node involvement (T3-4, N0, M0) have an average 5-year survival of approximately 70%. Patients with positive regional lymph nodes (any T, N1-3, M0) have an average 5-year survival of approximately 40%, while those with distant metastases (any T, any N, M1) have an average 5-year survival of approximately 5%.
According to the American Cancer Society statistics in 2006, over 20% of patients present with metastatic (stage IV) colorectal cancer at the time of diagnosis, and up to 25% of this group will have isolated liver metastasis that is potentially resectable. Lesions which undergo curative resection have demonstrated 5-year survival outcomes now exceeding 50%.
The aims of follow-up are to diagnose, in the earliest possible stage, any metastasis or tumors that develop later, but did not originate from the original cancer (metachronous lesions).
The U.S. National Comprehensive Cancer Network and American Society of Clinical Oncology provide guidelines for the follow-up of colon cancer. A medical history and physical examination are recommended every 3 to 6 months for 2 years, then every 6 months for 5 years. Carcinoembryonic antigen blood level measurements follow the same timing, but are only advised for patients with T2 or greater lesions who are candidates for intervention. A CT-scan of the chest, abdomen and pelvis can be considered annually for the first 3 years for patients who are at high risk of recurrence (for example, patients who had poorly differentiated tumors or venous or lymphatic invasion) and are candidates for curative surgery (with the aim to cure). A colonoscopy can be done after 1 year, except if it could not be done during the initial staging because of an obstructing mass, in which case it should be performed after 3 to 6 months. If a villous polyp, a polyp >1 centimeter or high grade dysplasia is found, it can be repeated after 3 years, then every 5 years. For other abnormalities, the colonoscopy can be repeated after 1 year.
Routine PET or ultrasound scanning, chest X-rays, complete blood count or liver function tests are not recommended. These guidelines are based on recent meta-analyses showing intensive surveillance and close follow-up can reduce the 5-year mortality rate from 37% to 30%.
Globally more than 1 million people get colorectal cancer every year resulting in about 715,000 deaths as of 2010 up from 490,000 in 1990. As of 2008 it is the second most common cause of cancer in women and the third most common in men with it being the fourth most common cause of cancer death after lung, stomach, and liver cancer. It is more common in developed than developing countries. Globally incidences vary 10-fold with highest rates in the Australia, New Zealand, Europe and the US and lowest rates in Africa and South-Central Asia.
Based on rates from 2007-2009, 4.96% of US men and women born today will be diagnosed with colorectal cancer during their lifetime. From 2005-2009, the median age at diagnosis for cancer of the colon and rectum in the US was 69 years of age. Approximately 0.1% were diagnosed under age 20; 1.1% between 20 and 34; 4.0% between 35 and 44; 13.4% between 45 and 54; 20.4% between 55 and 64; 24.0% between 65 and 74; 25.0% between 75 and 84; and 12.0% 85+ years of age. Rates are higher among males (54 per 100,000 c.f. 40 per 100,000 for females).
In the United States, March is colorectal cancer awareness month.
A number of substances are under study to reduce the risk of colon cancer including sea cucumber-derived bioactive sphingolipids.
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Stomach cancer, or gastric cancer, refers to cancer arising from any part of the stomach. Stomach cancer causes about 800,000 deaths worldwide per year. Prognosis is poor (5-year survival <5 to 15%) because most patients present with advanced disease.
Stomach cancer is often either asymptomatic (producing no noticeable symptoms) or it may cause only nonspecific symptoms (symptoms which are not specific to just stomach cancer, but also to other related or unrelated disorders) in its early stages. By the time symptoms occur, the cancer has often reached an advanced stage (see below) and may have also metastasized (spread to other, perhaps distant, parts of the body), which is one of the main reasons for its relatively poor prognosis.][ Stomach cancer can cause the following signs and symptoms:
Note that these can be symptoms of other problems such as a stomach virus, gastric ulcer or tropical sprue.
Most stomach cancer is caused by Helicobacter pylori infection. Dietary factors are not proven causes, but some foods, such as smoked foods, salted fish and meat, and pickled vegetables are associated with a higher risk. Nitrates and nitrites in cured meats can be converted by certain bacteria, including H. pylori, into compounds that have been found to cause stomach cancer in animals. On the other hand, the American Cancer Society recommends eating fresh fruits and vegetables that contain antioxidant vitamins, such as A and C, and says that they lower the risk of stomach cancer, and a Mediterranean diet is associated with lower rates of stomach cancer.
Smoking increases the risk of developing gastric cancer significantly, from 40% increased risk for current smokers to 82% increase for heavy smokers. Gastric cancers due to smoking mostly occur in the upper part of the stomach near the esophagus Some studies show increased risk with alcohol consumption as well.
Other factors associated with increased risk are autoimmune atrophic gastritis, pernicious anemia, Menetrier's disease (hyperplastic, hypersecretory gastropathy), intestinal metaplasia, and genetic factors.
H. pylori is the main risk factor in 65–80% of gastric cancers, but in only 2% of such infections. The mechanism by which H. pylori induces stomach cancer potentially involves chronic inflammation, or the action of H. pylori virulence factors such as CagA. Approximately ten percent of cases show a genetic component. Some studies indicate that bracken consumption and spores are correlated with incidence of stomach cancer, though causality has yet to be established.
Gastric cancer shows a male predominance in its incidence as up to three males are affected for every female. Estrogen may protect women against the development of this cancer form. A very small percentage of diffuse-type gastric cancers (see Histopathology below) are thought to be genetic. Hereditary diffuse gastric cancer (HDGC) has recently been identified and research is ongoing. However, genetic testing and treatment options are already available for families at risk.
The International Cancer Genome Consortium is leading efforts to map stomach cancer's complete genome.][
To find the cause of symptoms, the doctor asks about the patient's medical history, does a physical exam, and may order laboratory studies. The patient may also have one or all of the following exams:
Abnormal tissue seen in a gastroscope examination will be biopsied by the surgeon or gastroenterologist. This tissue is then sent to a pathologist for histological examination under a microscope to check for the presence of cancerous cells. A biopsy, with subsequent histological analysis, is the only sure way to confirm the presence of cancer cells.
Various gastroscopic modalities have been developed to increase yield of detected mucosa with a dye that accentuates the cell structure and can identify areas of dysplasia. Endocytoscopy involves ultra-high magnification to visualize cellular structure to better determine areas of dysplasia. Other gastroscopic modalities such as optical coherence tomography are also being tested investigationally for similar applications.
A number of cutaneous conditions are associated with gastric cancer. A condition of darkened hyperplasia of the skin, frequently of the axilla and groin, known as acanthosis nigricans, is associated with intra-abdominal cancers such as gastric cancer. Other cutaneous manifestations of gastric cancer include tripe palms (a similar darkening hyperplasia of the skin of the palms) and the Leser-Trelat sign, which is the rapid development of skin lesions known as seborrheic keratoses.
Various blood tests may be done, including: Complete Blood Count (CBC) to check for anemia. Also, a stool test may be performed to check for blood in the stool.
If cancer cells are found in the tissue sample, the next step is to stage, or find out the extent of the disease. Various tests determine whether the cancer has spread and, if so, what parts of the body are affected. Because stomach cancer can spread to the liver, the pancreas, and other organs near the stomach as well as to the lungs, the doctor may order a CT scan, a PET scan, an endoscopic ultrasound exam, or other tests to check these areas. Blood tests for tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) may be ordered, as their levels correlate to extent of metastasis, especially to the liver, and the cure rate.
Staging may not be complete until after surgery. The surgeon removes nearby lymph nodes and possibly samples of tissue from other areas in the abdomen for examination by a pathologist.
The clinical stages of stomach cancer are:
The TNM staging system is also used.
In a study of open-access endoscopy in Scotland, patients were diagnosed 7% in Stage I 17% in Stage II, and 28% in Stage III. A Minnesota population was diagnosed 10% in Stage I, 13% in Stage II, and 18% in Stage III. However in a high-risk population in the Valdivia Province of southern Chile, only 5% of patients were diagnosed in the first two stages and 10% in stage III.
Cancer of the stomach is difficult to cure unless it is found in an early stage (before it has begun to spread). Unfortunately, because early stomach cancer causes few symptoms, the disease is usually advanced when the diagnosis is made. Treatment for stomach cancer may include surgery, chemotherapy, and/or radiation therapy. New treatment approaches such as biological therapy and improved ways of using current methods are being studied in clinical trials.][
Surgery is the most common treatment. The surgeon removes part or all of the stomach, as well as the surrounding lymph nodes, with the basic goal of removing all cancer and a margin of normal tissue. Depending on the extent of invasion and the location of the tumor, surgery may also include removal of part of the intestine or pancreas. Tumors in the lower part of the stomach may call for a Billroth I or Billroth II procedure.
Endoscopic mucosal resection (EMR) is a treatment for early gastric cancer (tumor only involves the mucosa) that has been pioneered in Japan, but is also available in the United States at some centers. In this procedure, the tumor, together with the inner lining of stomach (mucosa), is removed from the wall of the stomach using an electrical wire loop through the endoscope. The advantage is that it is a much smaller operation than removing the stomach. Endoscopic submucosal dissection (ESD) is a similar technique pioneered in Japan, used to resect a large area of mucosa in one piece. If the pathologic examination of the resected specimen shows incomplete resection or deep invasion by tumor, the patient would need a formal stomach resection.
Surgical interventions are currently curative in less than 40% of cases, and, in cases of metastasis, may only be palliative.
The use of chemotherapy to treat stomach cancer has no firmly established standard of care. Unfortunately, stomach cancer has not been particularly sensitive to these drugs, and chemotherapy, if used, has usually served to palliatively reduce the size of the tumor, relieve symptoms of the disease and increase survival time. Some drugs used in stomach cancer treatment have included: 5-FU (fluorouracil) or its analog capecitabine, BCNU (carmustine), methyl-CCNU (Semustine), and doxorubicin (Adriamycin), as well as Mitomycin C, and more recently cisplatin and taxotere, often using drugs in various combinations. The relative benefits of these different drugs, alone and in combination, are unclear. Clinical researchers have explored the benefits of giving chemotherapy before surgery to shrink the tumor, or as adjuvant therapy after surgery to destroy remaining cancer cells. Combination treatment with chemotherapy and radiation therapy has some activity in selected post surgical settings. For patients who have HER2 overexpressing metastatic gastric or gastroesophageal (GE) junction adenocarcinoma, who have not received prior treatment for their metastatic disease, the US Food and Drug Administration granted approval (2010 October) for trastuzumab (Herceptin, Genentech, Inc.) in combination with cisplatin and a fluoropyrimidine (capecitabine or 5-fluorouracil). This was based on an improvement of the median overall survival (OS) of 2.5 months with trastuzumab plus chemotherapy treatment compared to chemotherapy alone (BO18255 ToGA trial). The combination of Herceptin with chemotherapy for treating metastatic gastric cancer was also sanctioned by the European regulatory authorities (2010 January).
Radiation therapy (also called radiotherapy) is the use of high-energy rays to damage cancer cells and stop them from growing. When used, it is generally in combination with surgery and chemotherapy, or used only with chemotherapy in cases where the individual is unable to undergo surgery. Radiation therapy may be used to relieve pain or blockage by shrinking the tumor for palliation of incurable disease.
While previous studies of multimodality therapy (combinations of surgery, chemotherapy and radiation therapy) gave mixed results, the Intergroup 0116 (SWOG 9008) study showed a survival benefit to the combination of chemotherapy and radiation therapy in patients with nonmetastatic, completely resected gastric cancer. Patients were randomized after surgery to the standard group of observation alone, or the study arm of combination chemotherapy and radiation therapy. Those in the study arm receiving chemotherapy and radiation therapy survived on average 36 months; compared to 27 months with observation.
Stomach cancer is the fourth most common cancer worldwide with 930,000 cases diagnosed in 2002. It is more common in men and in developing countries. As of 2010 deaths have decreased slightly from 774,000 in 1990 to about 755,000 in 2010 however it remains the second leading cause of cancer death after lung cancer.
It represents roughly 2% (25,500 cases) of all new cancer cases yearly in the United States, but it is more common in other countries. It is the leading cancer type in Korea, with 20.8% of malignant neoplasms.
Metastasis occurs in 80-90% of individuals with stomach cancer, with a six month survival rate of 65% in those diagnosed in early stages and less than 15% of those diagnosed in late stages.
Less than 1 in every 50 people going to the doctor with indigestion have cancer. Out of 10 million people in the Czech Republic, only 3 new cases of stomach cancer in people under 30 years of age in 1999 were diagnosed. Other studies show that less than 5% of stomach cancers occur in people under 40 years of age with 81.1% of that 5% in the age-group of 30 to 39 and 18.9% in the age-group of 20 to 29.
For Taiwan (statistic not shown on the above map), the mortality was 11.75 per 100,000 (1996).
The stomach is a muscular organ of the gastrointestinal tract that holds food and begins the digestive process by secreting gastric juice. The most common cancers of the stomach are adenocarcinomas but other histological types have been reported. Signs vary but may include vomiting (especially if blood is present), weight loss, anemia, and lack of appetite. Bowel movements may be dark and tarry in nature. In order to determine whether cancer is present in the stomach, special X-rays and/or abdominal ultrasound may be performed. Gastroscopy, a test using an instrument called endoscope to examine the stomach, is a useful diagnostic tool that can also take samples of the suspected mass for histopathological analysis to confirm or rule out cancer. The most definitive method of cancer diagnosis is through open surgical biopsy. Most stomach tumors are malignant with evidence of spread to lymph nodes or liver, making treatment difficult. Except for lymphoma, surgery is the most frequent treatment option for stomach cancers but it is associated with significant risks.
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The International Union Against Cancer (UICC) – a Geneva-based NGO – and member organizations in 86 countries launched the five-year World Cancer Campaign (2007–2012) on World Cancer Day, February 4, 2007. Targeting parents, health-care professionals, and policymakers, the campaign presents a common theme: fostering healthy habits during childhood can help prevent cancer later in life.
Four key messages of the campaign are:
Every year, more than seven million people die from cancer and close to 11 million new cases are diagnosed. In 2006, cancer killed more people than AIDS, malaria, and tuberculosis combined. “Cancer strikes all segments of society in every country. The good news is cancer is largely preventable,” says Isabel Mortara, UICC executive director. “The first steps toward prevention are education and action. That needs to start with children. That’s why this campaign is so important.”
In addition to targeting individuals, the World Cancer Campaign encourages policy decision-makers to put cancer on the public agenda. “Cancer control can only be effective if given priority at the highest decision-making levels. Complacency and inaction on the part of the world community will effectively contribute to more than 10 million deaths every year by 2020,” says Dr Franco Cavalli, UICC president.
Former United States First Lady Barbara Bush, Her Royal Highness Lalla Salma of Morocco, Nigerian President Olusegun Obasanjo, and tennis star Steffi Graf are among those lending their voices to the World Cancer Campaign with encouragement for those touched by cancer.
The UICC is a global resource for action, with more than 270 member organizations in Africa, Asia-Pacific, Europe, Latin America, the Caribbean, the Middle East, and North America. Since 2006, the UICC has taken on the responsibility of coordinating World Cancer Day globally, supported by members, partners, the World Health Organization, the International Atomic Energy Agency, and the other international bodies.
Wipe Out Kids' Cancer (WOKC) is a non-profit, volunteer organization based in Dallas, Texas. It has raised funds and advocated for children with cancer since 1980.
Commemorating 30 years of progress in investing in pediatric cancer research, Wipe Out Kids' Cancer has raised over $3 million in the crusade against pediatric cancer. Since being founded in 1980, the survival rates for some cancers, such as Leukemia, have increased from less than 50% to nearly 90%. Several of the top cancer initiatives are programs that WOKC has supported over the years.
For many childhood cancers, the odds of survival are still less than 50%.][ Cancer remains the number one disease killer of American children and the number two killer after auto accidents. Every day 46 children will be diagnosed with cancer. Of those, 7 will not survive, and of those who do survive nearly 66% will struggle with chronic medical issues brought on by the treatment of their cancer.][ Wipe Out Kids Cancer strives to represent kids with cancer and be an advocate for them.
WOKC raises funds primarily through special events throughout the year. Our largest annual fundraising event is the American Airlines Kids Cancer Golf Classic. Held in the fall each year, golfers are treated to exceptional "goody" bags with BlackBerry phones and Bachendorf watches. In 2004, WOKC made national news as one of the golfers hit a hole-in-one to win a Maserati Spyder from Park Place Maserati. Over the past 5 years, the event has raised over $725,000 for Wipe Out Kids' Cancer.
WOKC's mainstay event is the Tom Thumb Run for the Children Fun Run and Addison Oktoberfest 5K, which is held in conjunction with the Town of Addison’s Oktoberfest celebration in September. Runners enjoy cash prizes from Amica Insurance, families enjoy a post-race party featuring Eddie Coker, and everyone receives free entry to Addison's Oktoberfest with registration.
In 2005, the Spirit of "Little Mo" Awards were introduced at a 25th Anniversary gala. The awards were created to honor community leaders who have committed to eradicating pediatric cancer. In 2008, the gala moved to spring, and appropriately changed its name to "Swing into Spring." The gala featured swing band dancing, the Spirit of "Little Mo" Awards, and an incredible auction. Ann Podeszwa chaired the 2008 event which netted over $125,000 for Wipe Out Kids' Cancer.
Breast cancer is a type of cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas, while those originating from lobules are known as lobular carcinomas. Breast cancer occurs in humans and other mammals. While the overwhelming majority of human cases occur in women, male breast cancer can also occur.
The benefit versus harms of breast cancer screening is controversial. The characteristics of the cancer determine the treatment, which may include surgery, medications (hormonal therapy and chemotherapy), radiation and/or immunotherapy. Surgery provides the single largest benefit, and to increase the likelihood of cure, several chemotherapy regimens are commonly given in addition. Radiation is used after breast-conserving surgery and substantially improves local relapse rates and in many circumstances also overall survival.
Worldwide, breast cancer accounts for 22.9% of all cancers (excluding non-melanoma skin cancers) in women. In 2008, breast cancer caused 458,503 deaths worldwide (13.7% of cancer deaths in women). Breast cancer is more than 100 times more common in women than in men, although men tend to have poorer outcomes due to delays in diagnosis.
Prognosis and survival rates for breast cancer vary greatly depending on the cancer type, stage, treatment, and geographical location of the patient. Survival rates in the Western world are high; for example, more than 8 out of 10 women (84%) in England diagnosed with breast cancer survive for at least 5 years. In developing countries, however, survival rates are much poorer.
The first noticeable symptom of breast cancer is typically a lump that feels different from the rest of the breast tissue. More than 80% of breast cancer cases are discovered when the woman feels a lump. The earliest breast cancers are detected by a mammogram. Lumps found in lymph nodes located in the armpits can also indicate breast cancer.
Indications of breast cancer other than a lump may include thickening different from the other breast tissue, one breast becoming larger or lower, a nipple changing position or shape or becoming inverted, skin puckering or dimpling, a rash on or around a nipple, discharge from nipple/s, constant pain in part of the breast or armpit, and swelling beneath the armpit or around the collarbone. Pain ("mastodynia") is an unreliable tool in determining the presence or absence of breast cancer, but may be indicative of other breast health issues.
Inflammatory breast cancer is a particular type of breast cancer which can pose a substantial diagnostic challenge. Symptoms may resemble a breast inflammation and may include itching, pain, swelling, nipple inversion, warmth and redness throughout the breast, as well as an orange-peel texture to the skin referred to as peau d'orange; the absence of a discernible lump may delay detection dangerously.
Another reported symptom complex of breast cancer is Paget's disease of the breast. This syndrome presents as skin changes resembling eczema, such as redness, discoloration, or mild flaking of the nipple skin. As Paget's disease of the breast advances, symptoms may include tingling, itching, increased sensitivity, burning, and pain. There may also be discharge from the nipple. Approximately half of women diagnosed with Paget's disease of the breast also have a lump in the breast.
In rare cases, what initially appears as a fibroadenoma (hard, movable non-cancerous lump) could in fact be a phyllodes tumor. Phyllodes tumors are formed within the stroma (connective tissue) of the breast and contain glandular as well as stromal tissue. Phyllodes tumors are not staged in the usual sense; they are classified on the basis of their appearance under the microscope as benign, borderline, or malignant.
Occasionally, breast cancer presents as metastatic disease—that is, cancer that has spread beyond the original organ. The symptoms caused by metastatic breast cancer will depend on the location of metastasis. Common sites of metastasis include bone, liver, lung and brain. Unexplained weight loss can occasionally herald an occult breast cancer, as can symptoms of fevers or chills. Bone or joint pains can sometimes be manifestations of metastatic breast cancer, as can jaundice or neurological symptoms. These symptoms are called non-specific, meaning they could be manifestations of many other illnesses.
Most symptoms of breast disorders, including most lumps, do not turn out to represent underlying breast cancer. Fewer than 20% of lumps, for example, are cancerous, and benign breast diseases such as mastitis and fibroadenoma of the breast are more common causes of breast disorder symptoms. Nevertheless, the appearance of a new symptom should be taken seriously by both patients and their doctors, because of the possibility of an underlying breast cancer at almost any age.
The primary risk factors for breast cancer are female sex and older age. Other potential risk factors include: lack of childbearing or lack of breastfeeding, higher levels of certain hormones, certain dietary patterns, and obesity.
Smoking tobacco appears to increase the risk of breast cancer, with the greater the amount smoked and the earlier in life that smoking began, the higher the risk. In those who are long-term smokers, the risk is increased 35% to 50%. A lack of physical activity has been linked to ~10% of cases.
The association between breast feeding and breast cancer has not been clearly determined; some studies have found support for an association while others have not. In the 1980s, the abortion–breast cancer hypothesis posited that induced abortion increased the risk of developing breast cancer. This hypothesis was the subject of extensive scientific inquiry, which concluded that neither miscarriages nor abortions are associated with a heightened risk for breast cancer. There may be an association between use of oral contraceptives and the development of premenopausal breast cancer, but whether oral contraceptives use may actually cause premenopausal breast cancer is a matter of debate. If there is indeed a link, the absolute effect is small. In those with mutations in the breast cancer susceptibility genes BRCA1 or BRCA2, or who have a family history of breast cancer, use of modern oral contraceptives does not appear to affect the subsequent] (subsequent to what?)[ risk of breast cancer.
There is a relationship between diet and breast cancer, including an increased risk with a high fat diet, alcohol intake, and obesity. Dietary iodine deficiency may also play a role.
Other risk factors include radiation, and shift-work. A number of chemicals have also been linked including: polychlorinated biphenyls, polycyclic aromatic hydrocarbons, organic solvents and a number of pesticides. Although the radiation from mammography is a low dose, it is estimated that yearly screening from 40 to 80 years of age will cause approximately 225 cases of fatal breast cancer per million women screened.
Some genetic susceptibility may play a minor role in most cases. Overall, however, genetics is believed to be the primary cause of 5–10% of all cases. In those with zero, one or two affected relatives, the risk of breast cancer before the age of 80 is 7.8%, 13.3%, and 21.1% with a subsequent mortality from the disease of 2.3%, 4.2%, and 7.6% respectively. In those with a first degree relative with the disease the risk of breast cancer between the age of 40 and 50 is double that of the general population.
In less than 5% of cases, genetics plays a more significant role by causing a hereditary breast–ovarian cancer syndrome. This includes those who carry the gene mutationBRCA2 and BRCA1. These mutations account for up to 90% of the total genetic influence with a risk of breast cancer of 60–80% in those affected. Other significant mutations include: p53 (Li–Fraumeni syndrome), PTEN (Cowden syndrome), and STK11 (Peutz–Jeghers syndrome), CHEK2, ATM, BRIP1, and PALB2. In 2012, researchers said that there are four genetically distinct types of the breast cancer and that in each type, hallmark genetic changes lead to many cancers.
Certain breast changes: atypical hyperplasia and lobular carcinoma in situ found in benign breast conditions such as fibrocystic breast changes are correlated with an increased breast cancer risk.][
Breast cancer, like other cancers, occurs because of an interaction between an environmental (external) factor and a genetically susceptible host. Normal cells divide as many times as needed and stop. They attach to other cells and stay in place in tissues. Cells become cancerous when they lose their ability to stop dividing, to attach to other cells, to stay where they belong, and to die at the proper time.
Normal cells will commit cell suicide (apoptosis) when they are no longer needed. Until then, they are protected from cell suicide by several protein clusters and pathways. One of the protective pathways is the PI3K/AKT pathway; another is the RAS/MEK/ERK pathway. Sometimes the genes along these protective pathways are mutated in a way that turns them permanently "on", rendering the cell incapable of committing suicide when it is no longer needed. This is one of the steps that causes cancer in combination with other mutations. Normally, the PTEN protein turns off the PI3K/AKT pathway when the cell is ready for cell suicide. In some breast cancers, the gene for the PTEN protein is mutated, so the PI3K/AKT pathway is stuck in the "on" position, and the cancer cell does not commit suicide.
Mutations that can lead to breast cancer have been experimentally linked to estrogen exposure.
Failure of immune surveillance, the removal of malignant cells throughout one's life by the immune system. Abnormal growth factor signaling in the interaction between stromal cells and epithelial cells can facilitate malignant cell growth. In breast adipose tissue, overexpression of leptin leads to increased cell proliferation and cancer.
In the United States, 10 to 20 percent of patients with breast cancer and patients with ovarian cancer have a first- or second-degree relative with one of these diseases. The familial tendency to develop these cancers is called hereditary breast–ovarian cancer syndrome. The best known of these, the BRCA mutations, confer a lifetime risk of breast cancer of between 60 and 85 percent and a lifetime risk of ovarian cancer of between 15 and 40 percent. Some mutations associated with cancer, such as p53, BRCA1 and BRCA2, occur in mechanisms to correct errors in DNA. These mutations are either inherited or acquired after birth. Presumably, they allow further mutations, which allow uncontrolled division, lack of attachment, and metastasis to distant organs. However there is strong evidence of residual risk variation that goes well beyond hereditary BRCA gene mutations between carrier families. This is caused by unobserved risk factors. This implicates environmental and other causes as triggers for breast cancers. The inherited mutation in BRCA1 or BRCA2 genes can interfere with repair of DNA cross links and DNA double strand breaks (known functions of the encoded protein) These carcinogens cause DNA damage such as DNA cross links and double strand breaks that often require repairs by pathways containing BRCA1 and BRCA2. However, mutations in BRCA genes account for only 2 to 3 percent of all breast cancers. Levin et al. say that cancer may not be inevitable for all carriers of BRCA1 and BRCA2 mutations. About half of hereditary breast–ovarian cancer syndromes involve unknown genes.
Most types of breast cancer are easy to diagnose by microscopic analysis of a sample—or biopsy—of the affected area of the breast. There are, however, rarer types of breast cancer that require specialized lab exams.
The two most commonly used screening methods, physical examination of the breasts by a healthcare provider and mammography, can offer an approximate likelihood that a lump is cancer, and may also detect some other lesions, such as a simple cyst. When these examinations are inconclusive, a healthcare provider can remove a sample of the fluid in the lump for microscopic analysis (a procedure known as fine needle aspiration, or fine needle aspiration and cytology—FNAC) to help establish the diagnosis. The needle aspiration may be performed in a healthcare provider's office or clinic using local anaesthetic if required.][ A finding of clear fluid makes the lump highly unlikely to be cancerous, but bloody fluid may be sent off for inspection under a microscope for cancerous cells. Together, physical examination of the breasts, mammography, and FNAC can be used to diagnose breast cancer with a good degree of accuracy.
Other options for biopsy include a core biopsy or vacuum-assisted breast biopsy, which are procedures in which a section of the breast lump is removed; or an excisional biopsy, in which the entire lump is removed. Very often the results of physical examination by a healthcare provider, mammography, and additional tests that may be performed in special circumstances (such as imaging by ultrasound or MRI) are sufficient to warrant excisional biopsy as the definitive diagnostic and primary treatment method.
Excised human breast tissue, showing an irregular, dense, white stellate area of cancer 2 cm in diameter, within yellow fatty tissue.
High-grade invasive ductal carcinoma, with minimal tubule formation, marked pleomorphism, and prominent mitoses, 40x field.
Micrograph showing a lymph node invaded by ductal breast carcinoma, with extension of the tumour beyond the lymph node.
Neuropilin-2 expression in normal breast and breast carcinoma tissue.
F-18 FDG PET/CT: A breast cancer metastasis to the right scapula
Breast cancers are classified by several grading systems. Each of these influences the prognosis and can affect treatment response. Description of a breast cancer optimally includes all of these factors.
In cases of breast cancer with low risk for metastasis, the risks associated with PET scans, CT scans, or bone scans outweigh the possible benefits. This is because these procedures expose the patient to a substantial amount of potentially dangerous ionizing radiation.
Women may reduce their risk of breast cancer by maintaining a healthy weight, drinking less alcohol, being physically active and breastfeeding their children. These modifications might prevent 38% of breast cancers in the US, 42% in the UK, 28% in Brazil and 20% in China. The benefits with moderate exercise such as brisk walking are seen at all age groups including postmenopausal women. Marine omega-3 polyunsaturated fatty acids appear to reduce the risk.
Removal of both breasts before any cancer has been diagnosed or any suspicious lump or other lesion has appeared (a procedure known as prophylactice bilateral mastectomy) may be considered in people with BRCA1 and BRCA2 mutations, which are associated with a substantially heightened risk for an eventual diagnosis of breast cancer.
The selective estrogen receptor modulators (such as tamoxifen) reduce the risk of breast cancer but increase the risk of thromboembolism and endometrial cancer. There is no overall change in the risk of death. The benefit of breast cancer reduction continues for at least five years after stopping a course of treatment with these medications.
Breast cancer screening refers to testing otherwise-healthy women for breast cancer in an attempt to achieve an earlier diagnosis under the assumption that early detection will improve outcomes. A number of screening test have been employed including: clinical and self breast exams, mammography, genetic screening, ultrasound, and magnetic resonance imaging.
A clinical or self breast exam involves feeling the breast for lumps or other abnormalities. Clinical breast exams are performed by health care providers, while self breast exams are performed by the person themselves. Evidence dose not support the effectiveness of either type of breast exam, as by the time a lump is large enough to be found it is likely to have been growing for several years and thus soon be large enough to be found without an exam. Mammographic screening for breast cancer uses X-rays to examine the breast for any uncharacteristic masses or lumps. During a screening, the breast is compressed and a technician takes photos from multiple angles. A general mammogram takes photos of the entire breast, while a diagnostic mammogram focuses on a specific lump or area of concern.
A number of national bodies continue to recommend breast cancer screening. For the average woman, the U.S. Preventive Services Task Force recommends mammography every two years in women between the ages of 50 and 74, the Council of Europe recommends mammography between 50 and 69 with most programs using a 2 year frequency, and in Canada screening is recommended between the ages of 50 and 74 at a frequency of 2 to 3 years. These task force reports point out that in addition to unnecessary surgery and anxiety, the risks of more frequent mammograms include a small but significant increase in breast cancer induced by radiation. Whether MRI as a screening method has greater harms or benefits when compared to standard mammography is not known.
The Cochrane Collaboration (2011) states that the best quality evidence neither demonstrates a reduction in either cancer specific, nor a reduction in all cause mortality from screening mammography. When less rigorous trials are added to the analysis there is a reduction in breast cancer specific mortality of 0.05% (a relative decrease of 15%). Screening results in a 30% increase in rates of over-diagnosis and over-treatment, resulting in the view that it is not clear whether mammography screening does more good or harm. Cochrane states that, due to recent improvements in breast cancer treatment, and the risks of false positives from breast cancer screening leading to unnecessary treatment, "it therefore no longer seems reasonable to attend for breast cancer screening" at any age.
The management of breast cancer depends on various factors, including the stage of the cancer. Increasingly aggressive treatments are employed in accordance with the poorer the patient's prognosis and the higher the risk of recurrence of the cancer following treatment.
Breast cancer is usually treated with surgery, which may be followed by chemotherapy or radiation therapy, or both. A multidisciplinary approach is preferable. Hormone receptor-positive cancers are often treated with hormone-blocking therapy over courses of several years. Monoclonal antibodies, or other immune-modulating treatments, may be administered in certain cases of metastatic and other advanced stages of breast cancer.
Surgery involves the physical removal of the tumor, typically along with some of the surrounding tissue. One or more lymph nodes may be biopsied during the surgery; increasingly the lymph node sampling is performed by a sentinel lymph node biopsy.
Standard surgeries include:
Once the tumor has been removed, if the patient desires, breast reconstruction surgery, a type of plastic surgery, may then be performed to improve the aesthetic appearance of the treated site. Alternatively, women use breast prostheses to simulate a breast under clothing, or choose a flat chest. Nipple/areola prostheses can be used at any time following the mastectomy.
Drugs used after and in addition to surgery are called adjuvant therapy. Chemotherapy or other types of therapy prior to surgery are called neoadjuvant therapy. Aspirin may reduce mortality from breast cancer.
There are currently three main groups of medications used for adjuvant breast cancer treatment: hormone blocking therapy, chemotherapy, and monoclonal antibodies.
Radiotherapy is given after surgery to the region of the tumor bed and regional lymph nodes, to destroy microscopic tumor cells that may have escaped surgery. It may also have a beneficial effect on tumor microenvironment. Radiation therapy can be delivered as external beam radiotherapy or as brachytherapy (internal radiotherapy). Conventionally radiotherapy is given after the operation for breast cancer. Radiation can also be given at the time of operation on the breast cancer- intraoperatively. The largest randomised trial to test this approach was the TAR-GIT-A Trial which found that targeted intraoperative radiotherapy was equally effective at 4-years as the usual several weeks' of whole breast external beam radiotherapy. Radiation can reduce the risk of recurrence by 50–66% (1/2 – 2/3 reduction of risk) when delivered in the correct dose and is considered essential when breast cancer is treated by removing only the lump (Lumpectomy or Wide local excision).
A prognosis is a prediction of outcome and the probability of progression-free survival (PFS) or disease-free survival (DFS). These predictions are based on experience with breast cancer patients with similar classification. A prognosis is an estimate, as patients with the same classification will survive a different amount of time, and classifications are not always precise. Survival is usually calculated as an average number of months (or years) that 50% of patients survive, or the percentage of patients that are alive after 1, 5, 15, and 20 years. Prognosis is important for treatment decisions because patients with a good prognosis are usually offered less invasive treatments, such as lumpectomy and radiation or hormone therapy, while patients with poor prognosis are usually offered more aggressive treatment, such as more extensive mastectomy and one or more chemotherapy drugs.
Prognostic factors are reflected in the classification scheme for breast cancer including stage, (i.e., tumor size, location, whether disease has spread to lymph nodes and other parts of the body), grade, recurrence of the disease, and the age and health of the patient. The Nottingham Prognostic Index is a commonly used prognostic tool.
The stage of the breast cancer is the most important component of traditional classification methods of breast cancer, because it has a greater effect on the prognosis than the other considerations. Staging takes into consideration size, local involvement, lymph node status and whether metastatic disease is present. The higher the stage at diagnosis, the poorer the prognosis. The stage is raised by the invasiveness of disease to lymph nodes, chest wall, skin or beyond, and the aggressiveness of the cancer cells. The stage is lowered by the presence of cancer-free zones and close-to-normal cell behaviour (grading). Size is not a factor in staging unless the cancer is invasive. For example, Ductal Carcinoma In Situ (DCIS) involving the entire breast will still be stage zero and consequently an excellent prognosis with a 10yr disease free survival of about 98%.
The breast cancer grade is assessed by comparison of the breast cancer cells to normal breast cells. The closer to normal the cancer cells are, the slower their growth and the better the prognosis. If cells are not well differentiated, they will appear immature, will divide more rapidly, and will tend to spread. Well differentiated is given a grade of 1, moderate is grade 2, while poor or undifferentiated is given a higher grade of 3 or 4 (depending upon the scale used). The most widely used grading system is the Nottingham scheme; details are provided in the discussion of breast cancer grade.
The presence of estrogen and progesterone receptors in the cancer cell is important in guiding treatment. Those who do not test positive for these specific receptors will not be able to respond to hormone therapy, and this can affect their chance of survival depending upon what treatment options remain, the exact type of the cancer, and how advanced the disease is.
In addition to hormone receptors, there are other cell surface proteins that may affect prognosis and treatment. HER2 status directs the course of treatment. Patients whose cancer cells are positive for HER2 have more aggressive disease and may be treated with the 'targeted therapy', trastuzumab (Herceptin), a monoclonal antibody that targets this protein and improves the prognosis significantly.
Younger women tend to have a poorer prognosis than post-menopausal women due to several factors. Their breasts are active with their cycles, they may be nursing infants, and may be unaware of changes in their breasts. Therefore, younger women are usually at a more advanced stage when diagnosed. There may also be biologic factors contributing to a higher risk of disease recurrence for younger women with breast cancer.
High mammographic breast density, which is a marker of increased risk of developing breast cancer, may not mean an increased risk of death among breast cancer patients, according to a 2012 report of a study involving 9232 women by the National Cancer Institute (NCI).
Since breast cancer in males is usually detected at later stages outcome are typically worse.
The emotional impact of cancer diagnosis, symptoms, treatment, and related issues can be severe. Most larger hospitals are associated with cancer support groups which provide a supportive environment to help patients cope and gain perspective from cancer survivors. Online cancer support groups are also very beneficial to cancer patients, especially in dealing with uncertainty and body-image problems inherent in cancer treatment.
Not all breast cancer patients experience their illness in the same manner. Factors such as age can have a significant impact on the way a patient copes with a breast cancer diagnosis. Premenopausal women with estrogen-receptor positive breast cancer must confront the issues of early menopause induced by many of the chemotherapy regimens used to treat their breast cancer, especially those that use hormones to counteract ovarian function.
On the other hand, a small 2007 study conducted by researchers at the College of Public Health of the University of Georgia suggested a need for greater attention to promoting functioning and psychological well-being among older cancer survivors, even when they may not have obvious cancer-related medical complications. The study found that older breast cancer survivors showed multiple indications of decrements in their health-related quality of life, and lower psychosocial well-being than a comparison group. Survivors reported no more depressive symptoms or anxious mood than the comparison group, however, they did score lower in measures of positive psychosocial well-being, and reported more depressed mood and days affected by fatigue. As the incidence of breast cancer in women over 50 rises and survival rates increase, breast cancer is increasingly becoming a geriatric issue that warrants both further research and the expansion of specialized cancer support services tailored for specific age groups.
The NPI Nottingham Prognostic Index is a useful tool in assessing the prognosis
Worldwide, breast cancer is the most common invasive cancer in women. (The most common form of cancer is non-invasive non-melanoma skin cancer; non-invasive cancers are generally easily cured, cause very few deaths, and are routinely excluded from cancer statistics.) Breast cancer comprises 22.9% of invasive cancers in women and 16% of all female cancers.
In 2008, breast cancer caused 458,503 deaths worldwide (13.7% of cancer deaths in women and 6.0% of all cancer deaths for men and women together). Lung cancer, the second most common cause of cancer-related death in women, caused 12.8% of cancer deaths in women (18.2% of all cancer deaths for men and women together).
The incidence of breast cancer varies greatly around the world: it is lowest in less-developed countries and greatest in the more-developed countries. In the twelve world regions, the annual age-standardized incidence rates per 100,000 women are as follows: in Eastern Asia, 18; South Central Asia, 22; sub-Saharan Africa, 22; South-Eastern Asia, 26; North Africa and Western Asia, 28; South and Central America, 42; Eastern Europe, 49; Southern Europe, 56; Northern Europe, 73; Oceania, 74; Western Europe, 78; and in North America, 90.
The number of cases worldwide has significantly increased since the 1970s, a phenomenon partly attributed to the modern lifestyles. Breast cancer is strongly related to age with only 5% of all breast cancers occurring in women under 40 years old.
Because of its visibility, breast cancer was the form of cancer most often described in ancient documents. Because autopsies were rare, cancers of the internal organs were essentially invisible to ancient medicine. Breast cancer, however, could be felt through the skin, and in its advanced state often developed into fungating lesions: the tumor would become necrotic (die from the inside, causing the tumor to appear to break up) and ulcerate through the skin, weeping fetid, dark fluid.
The oldest description of cancer was discovered in Egypt and dates back to approximately 1600 BC. The Edwin Smith Papyrus describes 8 cases of tumors or ulcers of the breast that were treated by cauterization. The writing says about the disease, "There is no treatment." For centuries, physicians described similar cases in their practices, with the same conclusion. Ancient medicine, from the time of the Greeks through the 17th century, was based on humoralism, and thus believed that breast cancer was generally caused by imbalances in the fundamental fluids that controlled the body, especially an excess of black bile. Alternatively, patients often saw it as divine punishment. In the 18th century, a wide variety of medical explanations were proposed, including a lack of sexual activity, too much sexual activity, physical injuries to the breast, curdled breast milk, and various forms of lymphatic blockages, either internal or due to restrictive clothing. In the 19th century, the Scottish surgeon John Rodman said that fear of cancer caused cancer, and that this anxiety, learned by example from the mother, accounted for breast cancer's tendency to run in families.
Although breast cancer was known in ancient times, it was uncommon until the 19th century, when improvements in sanitation and control of deadly infectious diseases resulted in dramatic increases in lifespan. Previously, most women had died too young to have developed breast cancer. Additionally, early and frequent childbearing and breastfeeding probably reduced the rate of breast cancer development in those women who did survive to middle age.
Because ancient medicine believed that the cause was systemic, rather than local, and because surgery carried a high mortality rate, the preferred treatments tended to be pharmacological rather than surgical. Herbal and mineral preparations, especially involving the poison arsenic, were relatively common.
Mastectomy for breast cancer was performed at least as early as AD 548, when it was proposed by the court physician Aetios of Amida to Theodora. It was not until doctors achieved greater understanding of the circulatory system in the 17th century that they could link breast cancer's spread to 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 radical mastectomies in 1882, helped greatly by advances in general surgical technology, such as aseptic technique and anesthesia. The Halsted radical mastectomy often involved removing both breasts, associated lymph nodes, and the underlying chest muscles. This often led to long-term pain and disability, but was seen as necessary in order to prevent the cancer from recurring. Before the advent of the Halsted radical mastectomy, 20-year survival rates were only 10%; Halsted's surgery raised that rate to 50%. Extending Halsted's work, Jerome Urban promoted superradical mastectomies, taking even more tissue, until 1963, when the ten-year survival rates proved equal to the less-damaging radical mastectomy.
Radical mastectomies remained the standard of care in America until the 1970s, but in Europe, breast-sparing procedures, often followed radiation therapy, were generally adopted in the 1950s. One reason for this striking difference in approach may be the structure of the medical professions: European surgeons, descended from the barber surgeon, were held in less esteem than physicians; in America, the surgeon was the king of the medical profession. Additionally, there were far more European women surgeons: Less than one percent of American surgical oncologists were female, but some European breast cancer wards boasted a medical staff that was half female. American health insurance companies also paid surgeons more to perform radical mastectomies than they did to perform more intricate breast-sparing surgeries.
Breast cancer staging systems were developed in the 1920s and 1930s.
During the 1970s, a new understanding of metastasis led to perceiving cancer as a systemic illness as well as a localized one, and more sparing procedures were developed that proved equally effective. Modern chemotherapy developed after World War II.
The French surgeon Bernard Peyrilhe (1737–1804) realized the first experimental transmission of cancer by injecting extracts of breast cancer into an animal.
Prominent women who died of breast cancer include Anne of Austria, the mother of Louis XIV of France; Mary Washington, mother of George, and Rachel Carson, the environmentalist.
The first case-controlled study on breast cancer epidemiology was done by Janet Lane-Claypon, who published a comparative study in 1926 of 500 breast cancer cases and 500 control patients of the same background and lifestyle for the British Ministry of Health.
In the 1980s and 1990s, thousands of women who had successfully completed standard treatment then demanded and received high-dose bone marrow transplants, thinking this would lead to better long-term survival. However, it proved completely ineffective, and 15–20% of women died because of the brutal treatment.
The 1995 reports from the Nurses' Health Study and the 2002 conclusions of the Women's Health Initiative trial conclusively proved that hormone replacement therapy significantly increased the incidence of breast cancer.
Before the 20th century, breast cancer was feared and discussed in hushed tones, as if it were shameful. As little could be safely done with primitive surgical techniques, women tended to suffer silently rather than seeking care. When surgery advanced, and long-term survival rates improved, women began raising awareness of the disease and the possibility of successful treatment. The "Women's Field Army", run by the American Society for the Control of Cancer (later the American Cancer Society) during the 1930s and 1940s was one of the first organized campaigns. In 1952, the first peer-to-peer support group, called "Reach to Recovery", began providing post-mastectomy, in-hospital visits from women who had survived breast cancer.
The breast cancer movement of the 1980s and 1990s developed out of the larger feminist movements and women's health movement of the 20th century. This series of political and educational campaigns, partly inspired by the politically and socially effective AIDS awareness campaigns, resulted in the widespread acceptance of second opinions before surgery, less invasive surgical procedures, support groups, and other advances in patient care.
A pink ribbon is the most prominent symbol of breast cancer awareness. Pink ribbons, which can be made inexpensively, are sometimes sold as fundraisers, much like poppies on Remembrance Day. They may be worn to honor those who have been diagnosed with breast cancer, or to identify products that the manufacturer would like to sell to consumers that are interested in breast cancer—usually white, middle-aged, middle-class and upper-class, educated women.
The pink ribbon is associated with individual generosity, faith in scientific progress, and a "can-do" attitude. It encourages consumers to focus on the emotionally appealing ultimate vision of a cure for breast cancer, rather than on the fraught path between current knowledge and any future cures.
Wearing or displaying a pink ribbon has been criticized by the opponents of this practice as a kind of slacktivism, because it has no practical positive effect and as hypocrisy among those who wear the pink ribbon to show good will towards women with breast cancer, but then oppose these women's practical goals, like patient rights and anti-pollution legislation. Critics say that the feel-good nature of pink ribbons and pink consumption distracts society from the lack of progress on preventing and curing breast cancer. It is also criticized for reinforcing gender stereotypes and objectifying women and their breasts. Breast Cancer Action launched the "Think Before You Pink" campaign, and charged that companies have co-opted the pink campaign to promote products that encourage breast cancer, such as high-fat Kentucky Fried Chicken and alcohol.
Breast cancer culture, or pink ribbon culture, is the set of activities, attitudes, and values that surround and shape breast cancer in public. The dominant values are selflessness, cheerfulness, unity, and optimism. Appearing to have suffered bravely is the passport into the culture.
The woman with breast cancer is given a cultural template that constrains her emotional and social responses into a socially acceptable discourse: She is to use the emotional trauma of being diagnosed with breast cancer and the suffering of extended treatment to transform herself into a stronger, happier and more sensitive person who is grateful for the opportunity to become a better person. Breast cancer therapy becomes a rite of passage rather than a disease. To fit into this mold, the woman with breast cancer needs to normalize and feminize her appearance, and minimize the disruption that her health issues cause anyone else. Anger, sadness and negativity must be silenced.
As with most cultural models, people who conform to the model are given social status, in this case as cancer survivors. Women who reject the model are shunned, punished and shamed.
The culture is criticized for treating adult women like little girls, as evidenced by "baby" toys such as pink teddy bears given to adult women.
The primary purposes or goals of breast cancer culture are to maintain breast cancer's dominance as the preëminent women's health issue, to promote the appearance that society is "doing something" effective about breast cancer, and to sustain and expand the social, political, and financial power of breast cancer activists.
Compared to other diseases or other cancers, breast cancer receives a proportionately greater share of resources and attention. In 2001 MP Ian Gibson, chairman of the House of Commons of the United Kingdom all party group on cancer stated "The treatment has been skewed by the lobbying, there is no doubt about that. Breast cancer sufferers get better treatment in terms of bed spaces, facilities and doctors and nurses." Breast cancer also receives significantly more media coverage than other, equally prevalent cancers, with a study by Prostate Coalition showing 2.6 breast cancer stories for each one covering cancer of the prostate. Ultimately there is a concern that favouring sufferers of breast cancer with disproportionate funding and research on their behalf may well be costing lives elsewhere. Partly because of its relatively high prevalence and long-term survival rates, research is biased towards breast cancer. Some subjects, such as cancer-related fatigue, have been studied little except in women with breast cancer.
One result of breast cancer's high visibility is that statistical results can sometimes be misinterpreted, such as the claim that one in eight women will be diagnosed with breast cancer during their lives—a claim that depends on the unrealistic assumption that no woman will die of any other disease before the age of 95. This obscures the reality, which is that about ten times as many women will die from heart disease or stroke than from breast cancer.
The emphasis on breast cancer screening may be harming women by subjecting them to unnecessary radiation, biopsies, and surgery. One-third of diagnosed breast cancers might recede on their own. Screening mammography efficiently finds non-life-threatening, asymptomatic breast cancers and pre-cancers, even while overlooking serious cancers. According to H. Gilbert Welch of the Dartmouth Institute for Health Policy and Clinical Practice, research on screening mammography has taken the "brain-dead approach that says the best test is the one that finds the most cancers" rather than the one that finds dangerous cancers.
Cancers found during or shortly after pregnancy appear at approximately the same rate as other cancers in women of a similar age. As a result, breast cancer is one of the more common cancers found during pregnancy, although it is still rare, because only about 1 in 1,000 pregnant women experience any sort of cancer.
Diagnosing a new cancer in a pregnant woman is difficult, in part because any symptoms are commonly assumed to be a normal discomfort associated with pregnancy. As a result, cancer is typically discovered at a somewhat later stage than average in many pregnant or recently pregnant women. Some imaging procedures, such as MRIs (magnetic resonance imaging), CT scans, ultrasounds, and mammograms with fetal shielding are considered safe during pregnancy; some others, such as PET scans are not.
Treatment is generally the same as for non-pregnant women. However, radiation is normally avoided during pregnancy, especially if the fetal dose might exceed 100 cGy. In some cases, some or all treatments are postponed until after birth if the cancer is diagnosed late in the pregnancy. Early deliveries to speed the start of treatment are not uncommon. Surgery is generally considered safe during pregnancy, but some other treatments, especially certain chemotherapy drugs given during the first trimester, increase the risk of birth defects and pregnancy loss (spontaneous abortions and stillbirths). Elective abortions are not required and do not improve the likelihood of the mother surviving or being cured.
Radiation treatments may interfere with the mother's ability to breastfeed her baby because it reduces the ability of that breast to produce milk and increases the risk of mastitis. Also, when chemotherapy is being given after birth, many of the drugs pass through breast milk to the baby, which could harm the baby.
Treatments are constantly evaluated in randomized, controlled trials, to evaluate and compare individual drugs, combinations of drugs, and surgical and radiation techniques. The latest research is reported annually at scientific meetings such as that of the American Society of Clinical Oncology, San Antonio Breast Cancer Symposium, and the St. Gallen Oncology Conference in St. Gallen, Switzerland. These studies are reviewed by professional societies and other organizations, and formulated into guidelines for specific treatment groups and risk category.
A considerable part of the current knowledge on breast carcinomas is based on in vivo and in vitro studies performed with breast cancer cell (BCC) lines. These provide an unlimited source of homogenous self-replicating material, free of contaminating stromal cells, and often easily cultured in simple standard media. The first line described, BT-20, was established in 1958. Since then, and despite sustained work in this area, the number of permanent lines obtained has been strikingly low (about 100). Indeed, attempts to culture BCC from primary tumors have been largely unsuccessful. This poor efficiency was often due to technical difficulties associated with the extraction of viable tumor cells from their surrounding stroma. Most of the available BCC lines issued from metastatic tumors, mainly from pleural effusions. Effusions provided generally large numbers of dissociated, viable tumor cells with little or no contamination by fibroblasts and other tumor stroma cells. Many of the currently used BCC lines were established in the late 1970s. A very few of them, namely MCF-7, T-47D, and MDA-MB-231, account for more than two-thirds of all abstracts reporting studies on mentioned BCC lines, as concluded from a Medline-based survey.
Mainly based on Lacroix and Leclercq (2004). For more data on the nature of TP53 mutations in breast cancer cell lines, see Lacroix et al. (2006).
NFAT transcription factors are implicated in breast cancer, more specifically in the process of cell motility at the basis of metastasis formation. Indeed NFAT1 (NFATC2) and NFAT5 are pro-invasive and pro-migratory in breast carcinoma and NFAT3 (NFATc4) is an inhibitor of cell motility. NFAT1 regulates the expression of the TWEAKR and its ligand TWEAK with the Lipocalin 2 to increase breast cancer cell invasion and NFAT3 inhibits Lipocalin 2 expression to blunt the cell invasion.
Liver cancer or hepatic cancer (from the Greek hēpar, meaning liver) is a cancer that originates in the liver. Liver cancers are malignant tumors that grow on the surface or inside the liver. Liver tumors are discovered on medical imaging equipment (often by accident) or present themselves symptomatically as an abdominal mass, abdominal pain, jaundice, nausea or liver dysfunction. Liver cancers should not be confused with liver metastases, which are cancers that originate from organs elsewhere in the body and migrate to the liver.
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). 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. Cancers that arise from the blood vessel cells in the liver are known as hemangioendotheliomas.
As well as mixed tumors, rarer forms of liver cancer include:
Risk factors for adults developing primary liver cancer:
Risk factors for children developing primary liver cancer:
Since hepatitis B or C is one of the main causes of liver cancer, childhood vaccination against hepatitis B may reduce the risk of liver cancer in the future. In the case of patients with cirrhosis, alcohol consumption is to be avoided.
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. 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.
Globally, as of 2010[update], liver cancer resulted in 754,000 deaths, up from 460,000 in 1990, making it the third leading cause of cancer death after lung and stomach. Of these deaths 340,000 were secondary to hepatitis B, 196,000 were secondary to hepatitis C, and 150,000 were secondary to alcohol.
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