Prevalence and distribution

Testicular cancer is most common among whites and rare among men of African descent.^[3] Testicular cancer is uncommon in Asia and Africa. Worldwide incidence has doubled since the 1960s, with the highest rates of prevalence in Scandinavia, Germany, and New Zealand.

Incidence among African Americans doubled from 1988 to 2001 with a bias towards seminoma. The lack of significant increase in the incidence of early-stage testicular cancer during this timeframe suggests that the overall increase was not due to heightened awareness of the disease.

Although testicular cancer is most common among men aged 15–40 years, it has three peaks: infancy, ages 25–40 years, and age 60 years.

Germ cell tumors of the testis are the most common cancer in young men between the ages of 15 and 35 years.

A major risk factor for the development of testis cancer is cryptorchidism (undescended testicles). Other risk factors include inguinal hernia^[4], mumps orchitis ^[5]. Physical activity is associated with decreased risk and sedentary lifestyle is associated with increased risk. Early onset of male characteristics is associated with increased risk. These may reflect endogenous or environmental hormone

Hepatocellular carcinoma

Hepatocellular carcinoma Classification and external resources

Hepatocellular carcinoma (HCC, also called malignant hepatoma) is a primary malignancy (cancer) of the liver. Most cases of HCC are secondary to either a viral hepatitide infection (hepatitis B or C) or cirrhosis (alcoholism being the most common cause of hepatic cirrhosis).^[1] In countries where hepatitis is not endemic, most malignant cancers in the liver are not primary HCC but metastasis (spread) of cancer from elsewhere in the body, e.g. the colon. Treatment options of HCC and prognosis are dependent on many factors but especially on tumor size and staging. Tumor grade is also important. High-grade tumors will have a poor prognosis, while low-grade tumors may go unnoticed for many years, as is the case in many other organs, such as the breast, where a ductal carcinoma in situ (or a lobular carcinoma in situ) may be present without any clinical signs and without correlate on routine imaging tests, although in some occasions it may be detected on more specialized imaging studies like MR mammography (it should be stated, however, that the sensitivity of this technique remains, even with current state-of-the-art technology, below 50%).

The usual outcome is poor, because only 10 - 20% of hepatocellular carcinomas can be removed completely using surgery. If the cancer cannot be completely removed, the disease is usually deadly within 3 to 6 months.^[2] This is partially due to late presentation with large tumours, but also the lack of medical expertise and facilities. This is a rare tumor in the United States. A new receptor tyrosine kinase inhibitor, sorafenib has been shown in a Spanish phase III clinical trial to double the lifespan of late stage HCC patients.

Testicular cancer

Testicular Cancer Classification and external resources

Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system.

In the United States, between 7,500 and 8,000 diagnoses of testicular cancer are made each year.^[1][2] Over his lifetime, a man's risk of testicular cancer is roughly 1 in 250 (four tenths of one percent, or 0.4 percent). It is most common among males aged 15–40 years, particularly those in their mid-twenties. Testicular cancer has one of the highest cure rates of all cancers: in excess of 90 percent; essentially 100 percent if it has not metastasized. Even for the relatively few cases in which malignant cancer has spread widely, chemotherapy offers a cure rate of at least 85 percent today. Not all lumps on the testicles are tumors, and not all tumors are malignant; there are many other conditions such as testicular microlithiasis, epididymal cysts, appendix testis (hydatid of Morgagni), and so on which may be painful but are non-cancerous.

Pancreatic Cancer

Pancreatic cancer is a disease in which malignant (cancer) cells form in the tissues of the pancreas.

The pancreas is a gland about 6 inches long that is shaped like a thin pear lying on its side. The wider end of the pancreas is called the head, the middle section is called the body, and the narrow end is called the tail. The pancreas lies behind the stomach and in front of the spine.

The pancreas has two main jobs in the body:

• To produce juices that help digest (break down) food.
• To produce hormones, such as insulin and glucagon, that help control blood sugar levels. Both of these hormones help the body use and store the energy it gets from food.

The digestive juices are produced by exocrine pancreas cells and the hormones are produced by endocrine pancreas cells. About 95% of pancreatic cancers begin in exocrine cells.

This summary provides information on exocrine pancreatic cancer. Refer to the PDQ summary on Islet Cell Tumors (Endocrine Pancreas) Treatment for information on endocrine pancreatic cancer.

Smoking and health history can affect the risk of developing pancreatic cancer.

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. People who think they may be at risk should discuss this with their doctor. Risk factors for pancreatic cancer include the following:

• Smoking.
• Long-standing diabetes.
• Chronic pancreatitis.
• Certain hereditary conditions, such as hereditary pancreatitis, multiple endocrine neoplasia type 1 syndrome, hereditary nonpolyposis colon cancer (HNPCC; Lynch syndrome), von Hippel-Lindau syndrome, ataxia-telangiectasia, and the familial atypical multiple mole melanoma syndrome (FAMMM).

Cervical cancer

Cervical cancer Classification and external resources

Cervical cancer is malignant cancer of the cervix uteri or cervical area. It may present with vaginal bleeding but symptoms may be absent until the cancer is in its advanced stages.^[1] Treatment consists of surgery (including local excision) in early stages and chemotherapy and radiotherapy in advanced stages of the disease.

Pap smear screening can identify potentially precancerous changes. Treatment of high grade changes can prevent the development of cancer. In developed countries, the widespread use of cervical screening programs has reduced the incidence of invasive cervical cancer by 50% or more.

Human papillomavirus (HPV) infection is a necessary factor in the development of nearly all cases of cervical cancer.^[1][2] HPV vaccine effective against the two strains of HPV that cause the most cervical cancer has been licensed in the U.S. and the EU. These two HPV strains together are currently responsible for approximately 70%^[3][4] of all cervical cancers. Since the vaccine only covers some high-risk types, women should seek regular Pap smear screening, even after vaccination

Prostate cancer

Prostate cancer is a disease in which cancer develops in the prostate, a gland in the male reproductive system. It occurs when cells of the prostate mutate and begin to multiply uncontrollably. These cells may metastasize (spread) from the prostate to other parts of the body, particularly the bones and lymph nodes. Prostate cancer may cause pain, difficulty in urinating, problems during sexual intercourse, erectile dysfunction. Other symptoms can potentially develop during later stages of the disease.

Rates of detection of prostate cancers vary widely across the world, with South and East Asia detecting less frequently than in Europe, and especially the United States.^[1] Prostate cancer develops most frequently in men over the age of fifty and is one of the most prevalent types of cancer in men. However, many men who develop prostate cancer never have symptoms, undergo no therapy, and eventually die of other causes. This is because cancer of the prostate is, in most cases, slow-growing, and because most of those affected are over the age of 60. Hence, they often die of causes unrelated to the prostate cancer, such as heart/circulatory disease, pneumonia, other unconnected cancers, or old age. Many factors, including genetics and diet, have been implicated in the development of prostate cancer. The presence of prostate cancer may be indicated by symptoms, physical examination, prostate specific antigen (PSA), or biopsy. There is concern about the accuracy of the PSA test and its usefulness in screening. Suspected prostate cancer is typically confirmed by taking a biopsy of the prostate and examining it under a microscope. Further tests, such as CT scans and bone scans, may be performed to determine whether prostate cancer has spread

Skin Cancer

skin cancer: Cancer that forms in tissues of the skin. There are several types of skin cancer. Skin cancer that forms in melanocytes (skin cells that make pigment) is called melanoma. Skin cancer that forms in basal cells (small, round cells in the base of the outer layer of skin) is called basal cell carcinoma. Skin cancer that forms in squamous cells (flat cells that form the surface of the skin) is called squamous cell carcinoma. Skin cancer that forms in neuroendocrine cells (cells that release hormones in response to signals from the nervous system) is called neuroendocrine carcinoma of the skin. Most skin cancers form in older people on parts of the body exposed to the sun or in people who have weakened immune systems.

Estimated new cases and deaths from skin (nonmelanoma) cancer in the United States in 2008:

	New cases: more than 1,000,000
	Deaths: less than 1,000

See the online booklet What You Need To Know About™ Skin Cancer to learn about skin cancer symptoms, diagnosis, treatment, and questions to ask the doctor.

Colorectal Cancer

Colorectal cancer in its early stages usually doesn't cause any symptoms. Symptoms occur later, when the cancer may be more difficult to treat. The most common symptoms include:

• Pain in the belly.
• Blood in your stool or very dark stools.
• A change in your bowel habits (such as more frequent stools or a feeling that your bowels are not emptying completely).
• Fatigue.
• In rare cases, unexplained weight loss.

Colon cancer may cause no symptoms. When there are symptoms, they may depend on where in the colon the cancer is.²

• The cecum and ascending colon, the first and second parts of the colon, are on the right side of your abdomen. Cancer in this area may bleed, causing blood in the stool and symptoms of anemia, including fatigue and weakness. The amount of blood may be small and so well mixed with stool that your stool may look normal. Sometimes cancer in this area does not cause many symptoms.
• The transverse colon, the third part, goes across your body from right to left. Cancer here may cause abdominal cramps.
• The descending colon, the fourth part, and the S-shaped sigmoid colon, the fifth part, are on the left side of your abdomen and join the rectum. Cancer here may cause narrower stools and bright red blood in the stool. Sometimes this blood is mistakenly thought to come from hemorrhoids.

Having these symptoms does not mean you have cancer. A number of other medical problems could cause similar symptoms, including:

• Irritable bowel syndrome, a common digestive problem that causes periods of stomach pain, cramping or bloating, and diarrhea or constipation.
• Other growths (polyps) in the large intestine that are not cancer.
• Diverticulitis, a condition in which pouches form in the wall of the colon and become painful, swollen, or infected.
• Infections that cause diarrhea, such as salmonella.
• Inflammatory bowel disease, such as Crohn's disease and ulcerative colitis, which cause swelling and sores in the intestines.
• Bleeding hemorrhoids.
• Ulcers of the rectum.

ovarian cancer

Symptoms

Even in its early stages ovarian cancer has symptoms. Research indicates that 95 percent of women with ovarian cancer had symptoms and 90 percent of women experienced symptoms with early-stage ovarian cancer. Symptoms vary from woman to woman and many times depend on the location of the tumor and its impact on the surrounding organs. Many of the symptoms mimic other conditions such as irritable bowel syndrome.

The Gynecologic Cancer Foundation, the Society of Gynecologic Oncologists and the American Cancer Society, with significant support from the Alliance formed a consensus statement on ovarian cancer. The Ovarian Cancer National Alliance has endorsed the consensus statement, which was announced in June 2007. The statement follows.

Historically ovarian cancer was called the “silent killer” because symptoms were not thought to develop until the chance of cure was poor. However, recent studies have shown this term is untrue and that the following symptoms are much more likely to occur in women with ovarian cancer than women in the general population. These symptoms include:

• Bloating
• Pelvic or abdominal pain
• Difficulty eating or feeling full quickly
• Urinary symptoms (urgency or frequency)

Women with ovarian cancer report that symptoms are persistent and represent a change from normal for their bodies. The frequency and/or number of such symptoms are key factors in the diagnosis of ovarian cancer. Several studies show that even early stage ovarian cancer can produce these symptoms.

Women who have these symptoms almost daily for more than a few weeks should see their doctor, preferably a gynecologist. Prompt medical evaluation may lead to detection at the earliest possible stage of the disease. Early stage diagnosis is associated with an improved prognosis.

Several other symptoms have been commonly reported by women with ovarian cancer. These symptoms include fatigue, indigestion, back pain, pain with intercourse, constipation and menstrual irregularities. However, these other symptoms are not as useful in identifying ovarian cancer because they are also found in equal frequency in women in the general population who do not have ovarian cancer.

Lung Cancer

1. Phosphates May Raise Lung Cancer Risk
   

   Dec. 30, 2008 -- New research suggests a possible link between lung cancer risk and phosphate. Phosphate is a nutrient found in nature. Phosphates are also added to a variety of processed foods, including some baking mixes, colas, meat and poultry products, cheeses, canned tuna, puddings, toothpaste

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2. Broccoli: A Smoker's Best Buddy?
   

   Nov. 18, 2008 -- Smokers and former smokers who eat lots of broccoli and other cruciferous vegetables may be less likely than other smokers to develop lung cancer. Researchers at Roswell Park Cancer Institute in Buffalo, N.Y. reported that news today in Washington, D.C. at an American Association of

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3. Lung Cancer Genes Raise Treatment Hopes
   

   Oct. 22, 2008 -- A huge study funded by the National Institutes of Health triples the number of genes linked to lung cancer and points toward new treatments. The study analyzed DNA sequences from 623 genes in tumor samples from 188 patients with lung adenocarcinoma, the most common form of lung canc

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4. Red Wine May Cut Risk of Lung Cancer
   

   Oct. 7, 2008 -- Red wine may reduce the risk of lung cancer in men, especially smokers, a new study shows. The study, published in Cancer Epidemiology Biomarkers and Prevention, used data from The California Men's Health Study, which includes 84,170 men between 45 and 69 who are members of the Kaise

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5. Lung Cancer in Nonsmokers: Men Die More
   

   Sept. 9, 2008 -- Researchers looking into lung cancers in nonsmokers have found that men seem to die from the disease more than women. The reasons for this are not clear from the study results. Researchers led by the American Cancer Society's Michael Thun, MD, looked at data to try to better underst

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6. Incense Linked to Airway Cancers
   

   Aug. 25, 2008 -- People who breathe burning incense over long periods have an increased risk of developing certain cancers, even if they don't smoke cigarettes, a new study shows. Long-term exposure to incense fumes was associated with an increased risk for most upper respiratory cancers, as well as

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7. Granite Countertops a Recipe for Danger?
   

   July 30, 2008 -- They are beautiful and durable, but do those pricey granite kitchen countertops so popular with home builders and renovators also pose a health risk? Some researchers say they might, but a group representing the granite industry counters that those claims are “alarmist” and that the

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8. Microchip Detects Tumor Cells in Blood
   

   July 2, 2008 -- An experimental technique for detecting and analyzing tumor cells in the blood has the potential to change the face of cancer treatment, researchers say. Developed by investigators at Massachusetts General Hospital, the microchip-based device has the ability to isolate and analyze ci

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9. Inoperable Lung Tumors Zapped
   

   June 17, 2008 -- A device that zaps tumors ups survival in patients with small, inoperable lung cancers, an international clinical trial suggests. The technique is called radiofrequency ablation or RFA. Riccardo Lencioni, MD, Robert Suh, MD, and colleagues used RFA to zap 183 lung tumors in 106 pati

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10. Blood Test May Spot Early Lung Cancer
    

    June 3, 2008 (Chicago) -- A simple blood test may be able to spot lung cancer in smokers long before symptoms develop, when there is still a chance of a cure, researchers report. Lung cancer is the leading cancer killer, taking the lives of more than 160,000 Americans last year, according to the Ame

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Treatment

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

In planning treatment, doctors can also use PCR tests like Oncotype DX or microarray tests like MammaPrint that predict breast cancer recurrence risk based on gene expression. In February 2007, the MammaPrint test became the first breast cancer predictor to win formal approval from the Food and Drug Administration. This is a new gene test to help predict whether women with early-stage breast cancer will relapse in 5 or 10 years, this could help influence how aggressively the initial tumor is treated.^[50]

Interstitial laser thermotherapy (ILT) is an innovative method of treating breast cancer in a minimally invasive manner and without the need for surgical removal, and with the absence of any adverse effect on the health and survival of the patient during intermediate followup.^[51]

Radiation treatment is also used to help destroy cancer cells that may linger after surgery. Radiation can reduce the risk of recurrence by 50-66% (1/2 - 2/3rds reduction of risk) when delivered in the correct dose.

Epidemiology and etiology

Epidemiological risk factors for a disease can provide important clues as to the etiology, or cause, of a disease. 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.^{[13][verification needed][14]}

Today, breast cancer, like other forms of cancer, is considered to be the final outcome of multiple environmental and hereditary factors. Some of these factors include:

1. Lesions to DNA such as genetic mutations. Mutations that can lead to breast cancer have been experimentally linked to estrogen exposure.^[15] Beyond the contribution of estrogen, research has implicated viral transformation and the contribution of ionizing radiation in causing genetic mutations.^{[citation needed]}
2. Failure of immune surveillance, a theory in which the immune system removes malignant cells throughout one's life.^[16]
3. Abnormal growth factor signaling in the interaction between stromal cells and epithelial cells can facilitate malignant cell growth. For example, tumors can induce blood vessel growth (angiogenesis) by secreting various growth factors further facilitating cancer growth.^{[citation needed]}
4. Inherited defects in DNA repair genes, such as BRCA1, BRCA2^[17] and p53.^{[citation needed]} People in less-developed countries report lower incidence rates than in developed countries.

Experts believe that 95 percent of inherited breast cancer can be traced to one of two genes, which they call Breast Cancer 1 (BRCA1) and Breast Cancer 2 (BRCA2). Hereditary breast cancers can take the form of a site-specific hereditary breast cancer- cancers affecting the breast only- or breast- ovarian and other cancer syndromes. Breast cancer can be inherited both from female and male relatives. ^[18]

Although many epidemiological risk factors have been identified, the cause of any individual breast cancer is often unknowable. In other words, epidemiological research informs the patterns of breast cancer incidence across certain populations, but not in a given individual. Due to breast cancer is vary in different racial and ethnic group. The primary risk factors that have been identified are sex,^[19] age,^[20] childbearing, hormones,^[21] a high-fat diet,^[22] alcohol intake,^[23][24] obesity,^[25] and environmental factors such as tobacco use, radiation^[17] and shiftwork

Signs and symptoms

Signs and symptoms

The first symptom, or subjective sign, of breast cancer is typically a lump that feels different from the surrounding breast tissue. According to the The Merck Manual, more than 80% of breast cancer cases are discovered when the woman feels a lump.^[7] According to the American Cancer Society, the first medical sign, or objective indication of breast cancer as detected by a physician, is discovered by mammogram.^[8] Lumps found in lymph nodes located in the armpits^[7] and/or collarbone^{[citation needed]} can also indicate breast cancer.

Indications of breast cancer other than a lump may include changes in breast size or shape, skin dimpling, nipple inversion, or spontaneous single-nipple discharge. Pain is an unreliable tool in determining the presence or absence of breast cancer, but may be indicative of other breast health issues such as mastodynia.^[8][7][9]

When breast cancer cells invade the dermal lymphatics—small lymph vessels in the skin of the breast—its presentation can resemble skin inflammation and thus is known as inflammatory breast cancer (IBC). Symptoms of inflammatory breast cancer include pain, swelling, warmth and redness throughout the breast, as well as an orange-peel texture to the skin referred to as peau d'orange.^[7]

Another reported symptom complex of breast cancer is Paget's disease of the breast. This syndrome presents as eczematoid skin changes such as redness and mild flaking of the nipple skin. As Paget's advances, symptoms may include tingling, itching, increased sensitivity, burning, and pain. There may also be discharge from the nipple. Approximately half of women diagnosed with Paget's also have a lump in the breast

References

1. ^ K. Podsypanina, Y.-C. N. Du, M. Jechlinger, L. J. Beverly, D. Hambardzumyan, H. Varmus, Seeding and propagation of untransformed mouse mammary cells in the lung. Science 321, 1841-1844 (2008).
2. ^ C. A. Klein, The metastasis cascade. Science 321, 1785-1787 (2008).
3. ^ N Engl J Med. 2008 Dec 25;359(26):2814-23. Molecular basis of metastasis. Chiang AC, Massagué J.
4. ^ ^{a b c d e} Kumar, Abbas, Fausto; Robbins and Cotran: Pathologic Basis of Disease; Elsevier, 7th ed.
5. ^ "Metastatic Cancer: Questions and Answers". National Cancer Institute. http://www.cancer.gov/cancertopics/factsheet/Sites-Types/metastatic. Retrieved on 2008-08-28.
6. ^ Robert Weinberg, The Biology of Cancer, cited in Basics: A mutinous group of cells on a greedy, destructive task, by Natalie Angier, New York Times, April 3, 2007
7. ^ Yoshida BA, Sokoloff MM, Welch DR, Rinker-Schaeffer CW (Nov 2000). "Metastasis-suppressor genes: a review and perspective on an emerging field". J Natl Cancer Inst. 92 (21): 1717–30. PMID 11058615. http://jnci.oxfordjournals.org/cgi/content/full/92/21/1717.
8. ^ Weidner N, Semple JP, Welch WR, Folkman J (Jan 1991). "Tumor angiogenesis and metastasis—correlation in invasive breast carcinoma". N Engl J Med. 324 (1): 1–8. PMID 1701519. http://content.nejm.org/cgi/content/abstract/324/1/1.
9. ^ ^{a b} Briasoulis E, Pavlidis N (1997). "Cancer of Unknown Primary Origin". Oncologist 2 (3): 142–152. PMID 10388044. http://theoncologist.alphamedpress.org/cgi/pmidlookup?view=long&pmid=10388044.
10. ^ ^{a b c d e f g h i j k} National Cancer Institute: Metastatic Cancer: Questions and Answers. Retrieved on 2008-11-01

Treatments for metastatic cancer

Treatment and survival is determined by whether or not a cancer is local or has spread to other locations. If the cancer spreads to other tissues and organs, it may decrease a patient's likelihood of survival. However, there are some cancers (i.e., leukemia, brain) that can kill without spreading at all.

When cancer has metastasized, it may be treated with radiosurgery, chemotherapy, radiation therapy, biological therapy, hormone therapy, surgery or a combination of these. The choice of treatment generally depends on the type of primary cancer, the size and location of the metastasis, the patient's age and general health, and the types of treatments used previously. In patients diagnosed with CUP, it is still possible to treat the disease even when the primary tumor cannot be located.

The treatment options currently available are rarely able to cure metastatic cancer, though some tumors, such as those found in testicular cancer, are usually still curable

[edit] Metastasis and primary cancer

It is theorized that metastasis always coincides with a primary cancer, and, as such, is a tumor that started from a cancer cell or cells in another part of the body. However, over 10% of patients presenting to oncology units will have metastases without a primary tumor found. In these cases, doctors refer to the primary tumor as "unknown" or "occult," and the patient is said to have cancer of unknown primary origin (CUP) or Unknown Primary Tumors (UPT). It is estimated that 3% of all cancers are of unknown primary origin.^[9] Studies have shown that, if simple questioning does not reveal the cancer's source (coughing up blood -'probably lung', urinating blood - 'probably bladder'), complex imaging will not either.^[9] In some of these cases a primary may appear later.

The use of immunohistochemistry has permitted pathologists to give an identity to many of these metastases. However, imaging of the indicated area only occasionally reveals a primary. In rare cases (e.g., of melanoma), no primary tumor is found, even on autopsy. It is therefore thought that some primary tumors can regress completely, but leave their metastases behind

Factors involved

Metastasis is a complex series of steps in which cancer cells leave the original tumor site and migrate to other parts of the body via the bloodstream or the lymphatic system. To do so, malignant cells break away from the primary tumor and attach to and degrade proteins that make up the surrounding extracellular matrix (ECM), which separates the tumor from adjoining tissue. By degrading these proteins, cancer cells are able to breach the ECM and escape. When oral cancers metastasize, they commonly travel through the lymph system to the lymph nodes in the neck. The body resists metastasis by a variety of mechanisms through the actions of a class of proteins known as metastasis suppressors, of which about a dozen are known.^[7]

Cancer researchers studying the conditions necessary for cancer metastasis have discovered that one of the critical events required is the growth of a new network of blood vessels, called tumor angiogenesis.^[8] It has been found that angiogenesis inhibitors would therefore prevent the growth of metastases.

Modes and sites of metastatic dispersal

Metastatic tumors are very common in the late stages of cancer. The spread of metastases may occur via the blood or the lymphatics or through both routes. The most common places for the metastases to occur are the lungs, liver, brain, and the bones.^[5] There is also a propensity for certain tumors to seed in particular organs. This was first discussed as the "seed and soil" theory by Stephen Paget over a century ago in 1889. For example, prostate cancer usually metastasizes to the bones. In a similar manner, colon cancer has a tendency to metastasize to the liver. Stomach cancer often metastasizes to the ovary in women, then it is called a Krukenberg tumor. It is difficult for cancer cells to survive outside their region of origin, so in order to metastasize they must find a location with similar characteristics.^{[citation needed]}

For example, breast tumor cells, which gather calcium ions from breast milk, metastasize to bone tissue, where they can gather calcium ions from bone. Malignant melanoma spreads to the brain, presumably because neural tissue and melanocytes arise from the same cell line in the embryo.^[6]

Cancer cells may spread to lymph nodes (regional lymph nodes) near the primary tumor. This is called nodal involvement, positive nodes, or regional disease. Localized spread to regional lymph nodes near the primary tumor is not normally counted as metastasis, although this is a sign of worse prognosis. Transport through lymphatics is the most common pathway for the initial dissemination of carcinomas. ^[4]

In addition to the above routes, metastasis may occur by direct seeding, e.g., in the peritoneal cavity or pleural cavity.^[4]

Metastasis

Metastasis (Greek: displacement, μετά=next + στάσις=placement, plural: metastases), or Metastatic disease, sometimes abbreviated mets, is the spread of a disease from one organ or part to another non-adjacent organ or part. Only malignant tumor cells and infections have the established capacity to metastasize; however, this is recently reconsidered by new research.^[1][2][3]

Cancer cells can "break away", "leak", or "spill" from a primary tumor, enter lymphatic and blood vessels, circulate through the bloodstream, and settle down to grow within normal tissues elsewhere in the body. Metastasis is one of three hallmarks of malignancy (contrast benign tumors).^[4] Most tumors and other neoplasms can metastasize, although in varying degrees (e.g., glioma and basal cell carcinoma rarely metastasize).^[4]

When tumor cells metastasize, the new tumor is called a secondary or metastatic tumor, and its cells are like those in the original tumor. This means, for example, that, if breast cancer metastasizes to the lung, the secondary tumor is made up of abnormal breast cells, not of abnormal lung cells. The tumor in the lung is then called metastatic breast cancer, not lung cancer.

Classification

Breast cancers are described along four different classification schemes, or groups, each based on different criteria and serving a different purpose:

• Pathology - Each tumor is classified by its histological (microscopic anatomy) appearance and other criteria.
• Grade of tumor - The histological grade of a tumor is determined by a pathologist under a microscope. A well-differentiated (low grade) tumor resembles normal tissue. A poorly differentiated (high grade) tumor is composed of disorganized cells and, therefore, does not look like normal tissue. Moderately differentiated (intermediate grade) tumors are somewhere in between.
• Protein & gene expression status - Currently, all breast cancers should be tested for expression, or detectable effect, of the estrogen receptor (ER), progesterone receptor (PR) and HER2/neu proteins. These tests are usually done by immunohistochemistry and are presented in a pathologist's report. The profile of expression of a given tumor helps predict its prognosis, or outlook, and helps an oncologist choose the most appropriate treatment. More genes and/or proteins may be tested in the future.
• Stage of a tumor - The currently accepted staging scheme for breast cancer is the TNM classification. This considers the Tumor itself, whether it has spread to lymph Nodes, and whether there are any Metastases to locations other than the breast and lymph nodes.

Breast cancer is usually, but not always, primarily classified by its histological appearance. Rare variants are defined on the basis of physical exam findings. For example, inflammatory breast cancer (IBC), a form of ductal carcinoma or malignant cancer in the ducts, is distinguished from other carcinomas by the inflamed appearance of the affected breast.^[6] In the future, some pathologic classifications may be changed. For example, a subset of ductal carcinomas may be re-named basal-like carcinoma (part of the "triple-negative" tumors).^[

Breast cancer

Breast cancer is a cancer that starts in the cells of the breast in women and men. Worldwide, breast cancer is the second most common type of cancer after lung cancer (10.4% of all cancer incidence, both sexes counted)^[1] and the fifth most common cause of cancer death.^[2] In 2004, breast cancer caused 519,000 deaths worldwide (7% of cancer deaths; almost 1% of all deaths).^[2]

Breast cancer is about 100 times as frequent among women as among men, but survival rates are equal in both sexes

Chemoprevention

The concept that medications could be used to prevent cancer is an attractive one, and many high-quality clinical trials support the use of such chemoprevention in defined circumstances.

Daily use of tamoxifen, a selective estrogen receptor modulator (SERM), typically for 5 years, has been demonstrated to reduce the risk of developing breast cancer in high-risk women by about 50%. A recent study reported that the selective estrogen receptor modulator raloxifene has similar benefits to tamoxifen in preventing breast cancer in high-risk women, with a more favorable side effect profile.^[74]

Raloxifene is a SERM like tamoxifen; it has been shown (in the STAR trial) to reduce the risk of breast cancer in high-risk women equally as well as tamoxifen. In this trial, which studied almost 20,000 women, raloxifene had fewer side effects than tamoxifen, though it did permit more DCIS to form.^[74]

Finasteride, a 5-alpha-reductase inhibitor, has been shown to lower the risk of prostate cancer, though it seems to mostly prevent low-grade tumors.^[75] The effect of COX-2 inhibitors such as rofecoxib and celecoxib upon the risk of colon polyps have been studied in familial adenomatous polyposis patients^[76] and in the general population.^[77][78] In both groups, there were significant reductions in colon polyp incidence, but this came at the price of increased cardiovascular toxicity

Vitamins

The idea that cancer can be prevented through vitamin supplementation stems from early observations correlating human disease with vitamin deficiency, such as pernicious anemia with vitamin B12 deficiency, and scurvy with Vitamin C deficiency. This has largely not been proven to be the case with cancer, and vitamin supplementation is largely not proving effective in preventing cancer. The cancer-fighting components of food are also proving to be more numerous and varied than previously understood, so patients are increasingly being advised to consume fresh, unprocessed fruits and vegetables for maximal health benefits.^[65]

Epidemiological studies have shown that low vitamin D status is correlated to increased cancer risk.^[66][67] However, the results of such studies need to be treated with caution, as they cannot show whether a correlation between two factors means that one causes the other (i.e. correlation does not imply causation).^[68] The possibility that Vitamin D might protect against cancer has been contrasted with the risk of malignancy from sun exposure. Since exposure to the sun enhances natural human production of vitamin D, some cancer researchers have argued that the potential deleterious malignant effects of sun exposure are far outweighed by the cancer-preventing effects of extra vitamin D synthesis in sun-exposed skin. In 2002, Dr. William B. Grant claimed that 23,800 premature cancer deaths occur in the US annually due to insufficient UVB exposure (apparently via vitamin D deficiency).^[69] This is higher than 8,800 deaths occurred from melanoma or squamous cell carcinoma, so the overall effect of sun exposure might be beneficial. Another research group^[70][71] estimates that 50,000–63,000 individuals in the United States and 19,000 - 25,000 in the UK die prematurely from cancer annually due to insufficient vitamin D.

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

Diet

Main article: Diet and cancer

The consensus on diet and cancer is that obesity increases the risk of developing cancer. Particular dietary practices often explain differences in cancer incidence in different countries (e.g. gastric cancer is more common in Japan, while colon cancer is more common in the United States. In this example the preceding consideration of Haplogroups are excluded). Studies have shown that immigrants develop the risk of their new country, often within one generation, suggesting a substantial link between diet and cancer.^[42] Whether reducing obesity in a population also reduces cancer incidence is unknown.

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

An invasive colorectal carcinoma (top center) in a colectomy specimen.

Proposed dietary interventions for primary cancer risk reduction generally gain support from epidemiological association studies. Examples of such studies include reports that reduced meat consumption is associated with decreased risk of colon cancer,^[43] and reports that consumption of coffee is associated with a reduced risk of liver cancer.^[44] Studies have linked consumption of grilled meat to an increased risk of stomach cancer,^[45] colon cancer,^[46] breast cancer,^[47] and pancreatic cancer,^[48] a phenomenon which could be due to the presence of carcinogens such as benzopyrene in foods cooked at high temperatures.

A 2005 secondary prevention study showed that consumption of a plant-based diet and lifestyle changes resulted in a reduction in cancer markers in a group of men with prostate cancer who were using no conventional treatments at the time.^[49] These results were amplified by a 2006 study in which over 2,400 women were studied, half randomly assigned to a normal diet, the other half assigned to a diet containing less than 20% calories from fat. The women on the low fat diet were found to have a markedly lower risk of breast cancer recurrence, in the interim report of December, 2006

Prevention & Modifiable ("lifestyle") risk factors

Cancer prevention is defined as active measures to decrease the incidence of cancer. This can be accomplished by avoiding carcinogens or altering their metabolism, pursuing a lifestyle or diet that modifies cancer-causing factors and/or medical intervention (chemoprevention, treatment of pre-malignant lesions). The epidemiological concept of "prevention" is usually defined as either primary prevention, for people who have not been diagnosed with a particular disease, or secondary prevention, aimed at reducing recurrence or complications of a previously diagnosed illness.

Modifiable ("lifestyle") risk factors

See also: Alcohol and cancer

A squamous cell carcinoma (the whitish tumor) near the bronchi in a lung specimen.

The vast majority of cancer risk factors are environmental or lifestyle-related in nature, leading to the claim that cancer is a largely preventable disease.^[38] Examples of modifiable cancer risk factors include alcohol consumption (associated with increased risk of oral, esophageal, breast, and other cancers), smoking (although 20% of women with lung cancer have never smoked, versus 10% of men^[39]), physical inactivity (associated with increased risk of colon, breast, and possibly other cancers), and being overweight / obese (associated with colon, breast, endometrial, and possibly other cancers). Based on epidemiologic evidence, it is now thought that avoiding excessive alcohol consumption may contribute to reductions in risk of certain cancers; however, compared with tobacco exposure, the magnitude of effect is modest or small and the strength of evidence is often weaker. Other lifestyle and environmental factors known to affect cancer risk (either beneficially or detrimentally) include certain sexually transmitted diseases (such as those conveyed by the human papillomavirus), the use of exogenous hormones, exposure to ionizing radiation and ultraviolet radiation, and certain occupational and chemical exposures.

Every year, at least 200,000 people die worldwide from cancer related to their workplace.^[40] Millions of workers run the risk of developing cancers such as lung cancer and mesothelioma from inhaling asbestos fibers and tobacco smoke, or leukemia from exposure to benzene at their workplaces.^[40] Currently, most cancer deaths caused by occupational risk factors occur in the developed world.^[40] It is estimated that approximately 20,000 cancer deaths and 40,000 new cases of cancer each year in the U.S. are attributable to occupation