CE: The basic of cancer

October 1, 2002

Pharmaceutical Representative

October 2002 CE.

This first article in a three-part series provides healthcare representatives with an understanding of the basics of cancer.

Judy Chase, Pharm.D., Division of Pharmacy, University of Texas, M.D. Anderson Cancer Center, Houston, TX; John J. Kavanagh, M.D., chief professor, section of gynecologic medical oncology, department of clinical investigation, University of Texas, M.D. Anderson Cancer Center; and Patton B. Saul, M.D., medical director and director of gynecologic oncology, Lewis-Gale Cancer Center, Salem, VA, clinical associate professor of gynecology and gynecologic oncology, University of Virginia School of Medicine, Charlottesville, VA, served as consultants for this article for the Certified Medical Representatives Institute Inc.

Learning Objectives

* Define the key epidemiological terms used in the study of cancer.

* Describe the process by which a tumor develops.

* List the three types of cancers and their tissues of origin.

* List possible ways to prevent cancer.

* Describe the ways in which cancer may be detected.

Cancer is the second leading cause of death in the United States. Approximately 85 million Americans alive today will eventually have cancer, or about one in three people according to present rates, affecting three out of four families.

This article focuses on basic information about cancer, including epidemiology and pathophysiology. It also discusses the prevention and early detection of cancer and its diagnosis and staging.

Epidemiology

Key epidemiological terms in the study of cancer are incidence, prevalence, mortality and survival.

Incidence is defined as the number of newly diagnosed cases of cancer in a specified period of time in a defined population. Incidence data collection focuses on two specific areas: demographic information and medical information. Demographic information includes factors such as age, gender, marital status and place of residence. Medical data include onset of illness, location and stage of tumor, histology (exact pathologic type), treatment, and survival over time.

Prevalence is the measurement of all cancer cases, both old and new, at a designated point in time. Cancer prevalence data are not routinely collected by the registries that collect incidence data and must be determined by conducting a special survey.

The cancer mortality rate is the number of deaths attributed to cancer in a specified time period and in a defined population. Mortality data enable researchers to determine trends over time in the magnitude of cancer versus other causes of death in the United States. Mortality data are also useful in evaluating the impact of advances in cancer treatment.

The connection between incidence data and mortality data is survival analysis, the observation over time of individuals with cancer and the calculation of their probability of dying over several time periods. Survival analysis is a useful measure of the end result of cancer treatment and can demonstrate improvements over time in cancer management.

When analyzed together, the data on incidence, prevalence, mortality and survival can be used to identify trends in cancer. Knowledge of these trends enables the healthcare community to target specific populations with education and prevention programs aimed at certain cancers.

Pathophysiology

Cancer is a general term for the abnormal growth of cells. A cancer cell has an abnormal chromosome resulting from genetic change or mutation. The altered gene on this chromosome starts sending a wrong or garbled message and the cell begins to grow rapidly. In normal circumstances, a set of genes tells the body when to "shut off" the growth mechanism. A cancer cell has no "off switch" - once growth begins, cancer cells continue to divide in an uncontrolled way, as shown in the accompanying figure on page 31. They multiply rapidly until they form a lump known as a cancerous or malignant tumor.

Benign tumors are quite common and do not invade or destroy surrounding tissues; as such, they do not typically cause a health problem. Malignant tumors, on the other hand, are life-threatening because they have the ability to invade tissues and destroy the host. The spread of cancer or its local manifestations from a primary (parent) site to distant secondary sites is called metastasis.

How cancer spreads. Three ways for cancer to spread are direct extension, metastasis through the blood (hematogenous spread) and metastasis through the lymphatic system.

In direct extension, the tumor grows and invades the organs and tissues adjacent to it. It tends to form roots, growing into layers of surrounding tissue. Tumor angiogenesis factors cause new capillary formation. Once a tumor becomes vascularized (has a blood supply), its growth rate increases. Rapid tumor growth creates a pressure that forces finger-like projections of cancer cells into adjacent tissues.

Tumors can also spread by metastasis through the blood. The metastatic process begins when the tumor reaches approximately 1 billion cells or 1 cm in size. At this point, the release of tumor angiogenesis factors stimulates the formation of capillaries, just as it does in direct extension, and the tumor becomes vascularized. Cancer cells then enter the bloodstream through the tumor's capillaries and circulate throughout the body. Once implanted into the vessel wall of the target organ, tumor cells exit from the organ's circulation and penetrate its tissue in a process known as extravasation.

A third way that cancer can spread is through the lymphatic system. Lymphatic vessels carry a liquid called lymph, which drains waste products that are then trapped by the lymph nodes. Tumor cells can easily spread into the lymphatic system, and may continue traveling in the lymphatic vessels to other parts of the body.

Classification of malignant tumors. There are generally three types of malignant tumors, which develop in three kinds of tissues: carcinomas, sarcomas, and lymphomas and leukemias.

Carcinomas develop in the tissues that line or cover the surface of internal organs and passageways (the epithelial layer). About 80% of human cancers are carcinomas. Sarcomas are soft-tissue or bone tumors. About 10% of human cancers are sarcomas. Sarcomas develop in supporting or connective tissues, such as muscles, bones, nerves, tendons or blood vessels. The same organ that develops a carcinoma can also develop a sarcoma, since the organ also has connective tissue in it. Malignant lymphoma is a cancer of the lymphoid tissue. One specific kind of tumor in this broad category is called Hodgkin's disease; all the rest are known as non-Hodgkin's lymphomas. The leukemias are characterized by the abnormal proliferation and release of leukocytes (white blood cells).

Possible causes of cancer. For many cancers, no definite cause is known, and there is probably more than one cause. Under one theory, some normal genes may be transformed into genes that promote the growth of cancer, known as oncogenes (the prefix onco means tumor). Most normal genes are not transformed, because of other genes known as suppressor genes. If suppressor genes are missing or not functioning, then the cancer-producing actions of the oncogenes may flourish. It is thought that we all have normal cells that contain oncogenes in the chromosomes. In most people, these oncogenes are never activated; they simply lie dormant throughout our lives. In some people, however, a mutation may occur because of some assault on the cell structure. A stimulus or chemical agent turns on a switch that activates several oncogenes. These oncogenes then begin to work together to transform a normal cell into a cancer cell.

Several theories have been proposed regarding the stimulus that prompts these genetic changes. It is possible that viruses may insert a viral oncogene into a cell, or they may act as a random mutating agent. Currently, the theory with the most support focuses on multiple "hits." In this theory, all cancers arise from at least two changes, or hits, to the genes in a cell. These hits build up until a breaking point is reached and the transformation to cancerous growth occurs.

The hits may come from chemicals or foreign substances that cause cancer, known as initiators or carcinogens. Other factors include heredity and weaknesses of the immune system. When two or more hits are combined (e.g., tobacco smoke and asbestos or cigarette smoking and alcohol), the chances of developing cancer are multiplied. Cancer is an additive process, with many different hits occurring and interacting over several years.

Prevention and early detection

In order to decrease the cancer death rate, specific guidelines for cancer prevention and early detection have been developed by the Atlanta-based American Cancer Society. The following are important factors to consider when addressing prevention of cancer:

* Tobacco in all its forms should be avoided. Tobacco has been associated with lung cancer, as well as with cancers of the mouth, pharynx, larynx, esophagus, pancreas, cervix, kidney and bladder.

* Cancer risk may be reduced by an overall dietary pattern that includes a high proportion of plant foods (fruits, vegetables, grains and beans), limited amounts of meat, dairy and other high-fat foods, and a balance of caloric intake and physical activity.

* Alcoholic beverages have been associated with various forms of cancer, particularly when combined with tobacco use; these include breast cancer, as well as cancers of the oral cavity, esophagus, larynx, head and neck, and possibly the liver and pancreas.

* An estimated 5% to 10% of all cancers result from hereditary predisposition.

* Socioeconomic factors may serve as barriers to primary prevention and healthcare access and may contribute to the higher incidence of cancer, delayed diagnosis, poor survival statistics and increased mortality rates reported among certain populations.

* The sun is the primary source of ultraviolet light exposure that is known to cause skin cancer; therefore, exposure should be limited, and protective measures (sunscreen, protective clothing) should be used.

* Research indicates an association between sexual lifestyles and various cancers. Common risk factors in women, for instance, include a high rate of sexually transmitted diseases, sex at an early age, multiple partners and exposure to high-risk partners.

Early detection guidelines - like prevention guidelines - have the potential to greatly extend our lives. Most early detection efforts are tests performed during a visit to a physician's office. Examples include the Pap test, pelvic exam and mammography for women. For men, they may include the digital rectal exam. Both men and women over the age of 50 should have periodic tests (every three to five years) such as the fecal occult blood test, flexible sigmoidoscopy, colonoscopy and double contrast barium enema.

Diagnosis and staging

A complete medical history and physical examination are important components of the initial diagnostic visit.

Several other technologies may be used to visualize or detect the tumor or sites of metastasis. These include x-rays, computed tomography, magnetic resonance imaging, nuclear medicine scans, positron emission tomography, and visualization with radioimmunoconjugates and endoscopy.

The patient's workup includes several common laboratory procedures, such as a complete blood count with differential analysis of white blood cells, blood chemistries, liver function tests, renal function tests and urinalysis. Blood samples may be taken to test for the presence of tumor markers. Tumor markers are hormones, enzymes or antigens produced by tumor cells that are measurable in the blood of a person with a malignancy.

Cytology tests may also be used to identify a tumor. Cytology is the examination of cells obtained from tissue scrapings, body fluids, secretions or washings. One of the most common cytology tests is the Pap test, which uses scrapings from the cervix to identify abnormal cervical cells.

When a tumor is discovered, tumor cells must be examined. During a biopsy, a portion of tissue, usually obtained by surgical procedure, is examined by a pathologist. A biopsy may also be performed during an endoscopic procedure, or under the guidance of computed tomography or ultrasound to ensure that suspicious areas are sampled. Once a piece of tissue or tumor is removed, the pathologist examines it to determine whether it is benign or malignant, the tissue type, and the tissue grade.

Grade is a classification of tumor cells based on cellular differentiation, or similarity to normal cells in structure, function and maturity. Tumors are classified as low, intermediate or high grade. A high-grade tumor is immature, poorly differentiated, fast-growing and aggressive, whereas a low-grade tumor is usually mature, well-differentiated, slow-growing and less aggressive.

Once a cancer diagnosis is confirmed by the pathologist, the next step is to determine the stage of the malignancy. An international staging classification system has been adopted that provides an agreed-upon set of criteria for all physicians.

The TNM system involves assessment of three basic components:

* The size of the primary tumor.

* The extent of involvement of the regional lymph nodes.

* The extent of metastasis.

Information from the general TNM classification is combined with the specific staging system for a particular cancer. Stage classifications have been developed for most cancers and are published in the Manual for Staging of Cancer.

Article Summary

* Cancer incidence is the number of newly diagnosed cases of cancer in a specified period of time in a defined population.

* Cancer prevalence is the measurement of all cancer cases, both old and new, at a designated point in time.

* The mortality rate is the number of deaths attributed to cancer in a specified time period and in a defined population.

* Survival analysis is the observation over time of individuals with cancer and the calculation of their probability of dying over several time periods.

* A cancer cell has an abnormal chromosome resulting from genetic change or mutation; this abnormal cell multiplies uncontrollably until it forms a malignant tumor.

* Unlike benign tumors, malignant tumors have the ability to invade tissues and destroy the host.

• Malignant tumors are spread through direct extension, metastasis through the blood and metastasis through the lymphatic system.

• The major classifications of malignant tumors are carcinomas, sarcomas, and lymphomas and leukemias.

* Possible causes of cancer include:

• Transformation of normal genes into oncogenes that promote growth of cancer.

• Stimuli that activate oncogenes, such as viruses, weakness of the immune system, or multiple hits from one or more carcinogens.

* The American Cancer Society has developed guidelines for cancer prevention and early detection.

* A complete medical history and physical examination are important components of the initial diagnostic visit.

* If a tumor is detected, a biopsy is performed to determine tumor grade and staging.

© 2002 The Certified Medical Representatives Institute Inc., Roanoke, VA 24018. All rights reserved. No part of this article may be reproduced by any method or in any form without written permission from the CMR Institute. Reprints of this article are available from the CMR Institute. Request Continuing Education article OM-1.

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