Society and culture

Cancer research is the intense scientific effort to understand disease processes and discover possible therapies.

Research about cancer causes focusses on the following issues:

• Agents (e.g. viruses) and events (e.g. mutations) which cause or facilitate genetic changes in cells destined to become cancer.


• The precise nature of the genetic damage, and the genes which are affected by it.


• The consequences of those genetic changes on the biology of the cell, both in generating the defining properties of a cancer cell, and in facilitating additional genetic events which lead to further progression of the cancer.

The improved understanding of molecular biology and cellular biology due to cancer research has led to a number of new, effective treatments for cancer since President Nixon declared "War on Cancer" in 1971. Since 1971 the United States has invested over $200 billion on cancer research; that total includes money invested by public and private sectors and foundations.^[122] Despite this substantial investment, the country has seen a five percent decrease in the cancer death rate (adjusting for size and age of the population) between 1950 and 2005.^[123]

Leading cancer research organizations and projects include the American Association for Cancer Research, the American Cancer Society (ACS), the American Society of Clinical Oncology, the European Organisation for Research and Treatment of Cancer, Cancer Research UK, ECCO - the European Cancer Organisation, the National Cancer Institute, theNational Comprehensive Cancer Network, and The Cancer Genome Atlas project at the NCI.

History

Hippocrates (ca. 460 BC – ca. 370 BC) described several kinds of cancers, referring to them with the Greek word carcinos (crab or crayfish), among others.^[109] This name comes from the appearance of the cut surface of a solid malignant tumour, with "the veins stretched on all sides as the animal the crab has its feet, whence it derives its name".^[110] Since it was against Greek tradition to open the body, Hippocrates only described and made drawings of outwardly visible tumors on the skin, nose, and breasts. Treatment was based on the humor theory of four bodily fluids (black and yellow bile, blood, and phlegm). According to the patient's humor, treatment consisted of diet, blood-letting, and/or laxatives. Through the centuries it was discovered that cancer could occur anywhere in the body, but humor-theory based treatment remained popular until the 19th century with the discovery of cells.

Engraving with two views of a Dutch woman who had a tumor removed from her neck in 1689.

Celsus (ca. 25 BC - 50 AD) translated carcinos into the Latin cancer, also meaning crab. Galen (2nd century AD) called benign tumoursoncos, Greek for swelling, reserving Hippocrates' carcinos for malignant tumours. He later added the suffix -oma, Greek for swelling, giving the name carcinoma.

The oldest known description and surgical treatment of cancer was discovered in Egypt and dates back to approximately 1600 BC. ThePapyrus describes 8 cases of ulcers of the breast that were treated by cauterization, with a tool called "the fire drill." The writing says about the disease, "There is no treatment."^[111]

In the 16th and 17th centuries, it became more acceptable for doctors to dissect bodies to discover the cause of death. The German professorWilhelm Fabry believed that breast cancer was caused by a milk clot in a mammary duct. The Dutch professor Francois de la Boe Sylvius, a follower of Descartes, believed that all disease was the outcome of chemical processes, and that acidic lymph fluid was the cause of cancer. His contemporary Nicolaes Tulp believed that cancer was a poison that slowly spreads, and concluded that it was contagious.^[112]

The first cause of cancer was identified by British surgeon Percivall Pott, who discovered in 1775 that cancer of the scrotum was a common disease among chimney sweeps. The work of other individual physicians led to various insights, but when physicians started working together they could make firmer conclusions.

With the widespread use of the microscope in the 18th century, it was discovered that the 'cancer poison' spread from the primary tumor through the lymph nodes to other sites ("metastasis"). This view of the disease was first formulated by the English surgeon Campbell De Morgan between 1871 and 1874.^[113] The use of surgery to treat cancer had poor results due to problems with hygiene. The renowned Scottish surgeon Alexander Monro saw only 2 breast tumor patients out of 60 surviving surgery for two years. In the 19th century, asepsisimproved surgical hygiene and as the survival statistics went up, surgical removal of the tumor became the primary treatment for cancer. With the exception of William Coley who in the late 19th century felt that the rate of cure after surgery had been higher before asepsis (and who injected bacteria into tumors with mixed results), cancer treatment became dependent on the individual art of the surgeon at removing a tumor. During the same period, the idea that the body was made up of various tissues, that in turn were made up of millions of cells, laid rest the humor-theories about chemical imbalances in the body. The age of cellular pathology was born.

The genetic basis of cancer was recognised in 1902 by the German zoologist Theodor Boveri, professor of zoology at Munich and later in Würzburg.^[114] He discovered a method to generate cells with multiple copies of the centrosome, a structure he discovered and named. He postulated that chromosomes were distinct and transmitted different inheritance factors. He suggested that mutations of the chromosomes could generate a cell with unlimited growth potential which could be passed onto its descendants. He proposed the existence of cell cycle check points, tumour suppressor genes and oncogenes. He speculated that cancers might be caused or promoted by radiation, physical or chemical insults or by pathogenic microorganisms.

1938 poster identifying surgery, x-raysand radium as the proper treatments for cancer.

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

A founding paper of cancer epidemiology was the work of Janet Lane-Claypon, who published a comparative study in 1926 of 500 breast cancer cases and 500 control patients of the same background and lifestyle for the British Ministry of Health. Her ground-breaking work on cancer epidemiology was carried on by Richard Doll and Austin Bradford Hill, who published "Lung Cancer and Other Causes of Death In Relation toSmoking. A Second Report on the Mortality of British Doctors" followed in 1956 (otherwise known as the British doctors study). Richard Doll left the London Medical Research Center (MRC), to start the Oxford unit for Cancer epidemiology in 1968. With the use of computers, the unit was the first to compile large amounts of cancer data. Modern epidemiological methods are closely linked to current^[when?] concepts of disease and public health policy. Over the past 50 years, great efforts have been spent on gathering data across medical practise, hospital, provincial, state, and even country boundaries to study the interdependence of environmental and cultural factors on cancer incidence.

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

Epidemiology

Death rate from malignant cancer per 100,000 inhabitants in 2004.^[99]

  no data

  ≤ 55

  55-80

  80-105

  105-130

  130-155

  155-180

  180-205

  205-230

  230-255

  255-280

  280-305

  ≥ 305

In 2008 approximately 12.7 million cancers were diagnosed (excluding non-melanoma skin cancers and other non-invasive cancers) and 7.6 million people died of cancer worldwide.^[3] Cancers as a group account for approximately 13% of all deaths each year with the most common being: lung cancer (1.3 million deaths), stomach cancer (803,000 deaths), colorectal cancer (639,000 deaths), liver cancer (610,000 deaths), and breast cancer (519,000 deaths).^[100] This makes invasive cancer the leading cause of death in the developed world and the second leading cause of death in the developing world.^[3] Over half of cases occur in the developing world.^[3]

Global cancer rates have been increasing primarily due to an aging population and lifestyle changes in the developing world.^[3] The most significant risk factor for developing cancer is old age.^[101] Although it is possible for cancer to strike at any age, most people who are diagnosed with invasive cancer are over the age of 65.^[101] According to cancer researcher Robert A. Weinberg, "If we lived long enough, sooner or later we all would get cancer."^[102] Some of the association between aging and cancer is attributed to immunosenescence,^[103]errors accumulated in DNA over a lifetime, and age-related changes in the endocrine system.^[104]

Some slow-growing cancers are particularly common. Autopsy studies in Europe and Asia have shown that up to 36% of people have undiagnosed and apparently harmless thyroid cancer at the time of their deaths, and that 80% of men develop prostate cancer by age 80.^[105][106] As these cancers, often very small, did not cause the person's death, identifying them would have represented overdiagnosis rather than useful medical care.

The three most common childhood cancers are leukemia (34%), brain tumors (23%), and lymphomas (12%).^[107] Rates of childhood cancer have increased between 0.6% per year between 1975 to 2002 in the United States^[108] and by 1.1% per year between 1978 and 1997 in Europe.^[107]

Prognosis

Cancer has a reputation as a deadly disease. Taken as a whole, about half of patients receiving treatment for invasive cancer (excluding carcinoma in situ and non-melanoma skin cancers) die from cancer or its treatment. However, the survival rates vary dramatically by type of cancer, with the range running from basically all patients surviving to almost no patients surviving.

Patients who receive a long-term remission or permanent cure may have physical and emotional complications from the disease and its treatment. Surgery may have amputated body parts or removed internal organs, or the cancer may have damaged delicate structures, like the part of the ear that is responsible for the sense of balance; in some cases, this requires extensive physical rehabilitation or occupational therapy so that the patient can walk or engage in other activities of daily living. Chemo brain is a usually short-term cognitive impairmentassociated with some treatments. Cancer-related fatigue usually resolves shortly after the end of treatment, but may be lifelong. Cancer-related pain may require ongoing treatment. Younger patients may be unable to have children. Some patients may be anxious or psychologically traumatized as a result of their experience of the diagnosis or treatment.

Survivors generally need to have regular medical screenings to ensure that the cancer has not returned, to manage any ongoing cancer-related conditions, and to screen for new cancers. Cancer survivors, even when permanently cured of the first cancer, have approximately double the normal risk of developing another primary cancer. Some advocates have promoted "survivor care plans"—written documents detailing the diagnosis, all previous treatment, and all recommended cancer screening and other care requirements for the future—as a way of organizing the extensive medical information that survivors and their future healthcare providers need.

Progressive and disseminated malignant disease harms the cancer patient's quality of life, and some cancer treatments, including common forms of chemotherapy, have severe side effects. In the advanced stages of cancer, many patients need extensive care, affecting family members and friends. Palliative care aims to improve the patient's immediate quality of life, regardless of whether further treatment is undertaken. Hospice programs assist patients similarly, especially when a terminally ill patient has rejected further treatment aimed at curing the cancer. Both styles of service offer home health nursing and respite care.

Predicting either short-term or long-term survival is difficult and depends on many factors. The most important factors are the particular kind of cancer and the patient's age and overall health. Medically frail patients with many comorbidities have lower survival rates than otherwise healthy patients. A centenarian is unlikely to survive for five years even if the treatment is successful. Patients who report a higher quality of life tend to survive longer.^[96] People with lower quality of life may be affected by major depressive disorder and other complications from cancer treatment and/or disease progression that both impairs their quality of life and reduces their quantity of life. Additionally, patients with worse prognoses may be depressed or report a lower quality of life directly because they correctly perceive that their condition is likely to be fatal.

In the developed world, one in three people will be diagnosed with invasive cancer during their lifetimes. If all people with cancer survived and cancer occurred randomly, the lifetime odds of developing a second primary cancer would be one in nine.^[97] However, cancer survivors have an increased risk of developing a second primary cancer, and the odds are about two in nine.^[97] About half of these second primaries can be attributed to the normal one-in-nine risk associated with random chance.^[97] The increased risk is believed to be primarily due to the same risk factors that produced the first cancer (such as the person's genetic profile, alcohol and tobacco use, obesity, and environmental exposures), and partly due to the treatment for the first cancer, which typically includes mutagenic chemotherapeutic drugs or radiation.^[97] Cancer survivors may also be more likely to comply with recommended screening, and thus may be more likely than average to detect cancers.^[97]

Despite strong social pressure to maintain an upbeat, optimistic attitude or act like a determined "fighter" to "win the battle", personality traits have no connection to survival

Management

Many management options for cancer exist including: chemotherapy, radiation therapy, surgery, immunotherapy, monoclonal antibody therapy and other methods. Which treatments are used depends upon the type of cancer, the location and grade of the tumor, and the stage of the disease, as well as the general state of a person's health.

Complete removal of the cancer without damage to the rest of the body is the goal of treatment for most cancers. Sometimes this can be accomplished by surgery, but the propensity of cancers to invade adjacent tissue or to spread to distant sites by microscopic metastasis often limits its effectiveness. Surgery often required the removal of a wide surgical margin or afree margin. The width of the free margin depends on the type of the cancer, the method of removal (CCPDMA, Mohs surgery, POMA, etc.). The margin can be as little as 1 mm for basal cell cancer using CCPDMA or Mohs surgery, to several centimeters for aggressive cancers. The effectiveness of chemotherapy is often limited by toxicity to other tissues in the body. Radiation can also cause damage to normal tissue.

Because cancer is a class of diseases,^[82][83] it is unlikely that there will ever be a single "cure for cancer" any more than there will be a single treatment for all infectious diseases.^[84]Angiogenesis inhibitors were once thought to have potential as a "silver bullet" treatment applicable to many types of cancer, but this has not been the case in practice.^[85]

Experimental cancer treatments are treatments that are being studied to see whether they work. Typically, these are studied in clinical trials to compare the proposed treatment to the best existing treatment. They may be entirely new treatments, or they may be treatments that have been used successfully in one type of cancer, and are now being tested to see whether they are effective in another type.^[86] More and more, such treatments are being developed alongside companion diagnostic tests to target the right drugs to the right patients, based on their individual biology.^[87]

Alternative treatments

Alternative cancer treatments are treatments used by alternative medicine practitioners. These are a group of non-related interventions that do not fit the rigors of Western medicine and include mind–body interventions, herbal preparations, massage, acupuncture, reiki, electrical stimulation devices, and a variety of strict dietary regimens among others.

Alternative cancer treatments have never been shown to be effective at killing cancer cells in research studies, but remain popular in some cultures and religions. Some are dangerous, but most are harmless or provide the patient with a degree of physical or emotional comfort. Alternative cancer treatment has also been a fertile field for hoaxes aimed at stripping desperate patients of their money.^[88]

Many physicians are supportive of patients using alternative medicine in addition to standard management, especially for symptom management, though certain types of alternative herbs or diets could actually interfere with treatments and should be discussed with an oncologist if undergoing chemotherapy or radiation treatments.^{[89][90][91][92]}

Palliative care

Palliative care is a multidisciplinary approach to symptom management that aims to reduce the physical, emotional, spiritual, and psycho-social distress experienced by people with cancer. Unlike treatment that is aimed at directly killing cancer cells, the primary goal of palliative care is to make the person feel better as soon as possible.

Palliative care is often confused with hospice and therefore only involved when patients approach end of life. Like hospice care, palliative care attempts to help the person cope with the immediate needs and to increase the person's comfort. Unlike hospice care, palliative care does not require patients to stop treatment aimed at prolonging their lives or curing the cancer.

Multiple national medical guidelines recommend early palliative care involvement in people whose cancer has produced complex symptoms (pain, shortness of breath, fatigue, nausea) or who need help coping with their illness. In people who have metastatic disease when first diagnosed, oncologists should consider a palliative care consult immediately. Additionally, an oncologist should consider a palliative care consult in any patient they feel has a prognosis of less than 12 months even if continuing aggressive treatment.