Counseling About Cancer: Strategies for Genetic Counseling

Cancer Epidemiology

The problem may be briefly stated: What does: median mortality of eight months signify in our vernacular? I suspect that most people, without training in statistics, would read such a statement as I will probably be dead in eight months—the very conclusion that must be avoided, since it isn’t so and since attitude matters so much. … When I learned about the eight-month median, my first intellectual reaction was: fine, half the people will live longer, now what are my chances of being in that half.

(Gould, 2004, pp. 139–140)

Cancer epidemiologists seek to answer the question, Why did these people develop these particular cancers at this time? Cancer epidemiology is the study of cancer incidence and mortality within a population. This chapter provides current cancer statistics and a description of the many known or suspected causes of cancer.

1.1. CANCER STATISTICS

This section describes the incidence and mortality rates of specific cancers, and the differences in cancer rates by ethnic group and geographic location. First, here is a brief review of the terminology commonly used in cancer statistics.

Incidence—This refers to the number of new events (i.e., cancer diagnoses or deaths) that have occurred in a defined population during a specified period of time. This is the term most frequently used in reports of cancer statistics. For example, in the fictitious city of Madison, there were 14,000 new cases of lung cancer in 2008. Therefore, the 2008 incidence of lung cancer in Madison is 14,000.

Prevalence—This is the number of disease cases (i.e., cancer cases) in a defined population at a designated time. Prevalence includes both individuals newly diagnosed with cancer (incidence) and those who are survivors of the disease. Thus, cancers with high survival rates will have higher prevalence within a population than malignancies that cause rapid mortality. For example, in Madison, there were 14,000 new cases of lung cancer in 2008 and 5000 lung cancer survivors. Thus, the 2008 prevalence of lung cancer in Madison is 19,000.

Rate—This is a way of measuring disease frequency that allows comparisons between populations or subsets of populations. Frequently used examples include the incidence rate, prevalence rate, and cancer survival rate. To obtain the incidence rate, divide the number of new cases over a fixed time interval by the number of people in the population during that time. It is also conventional to use a denominator of fixed size in order to compare the rate to other disorders or populations. For example, 14,000 new cases of lung cancer were diagnosed in Madison, which has a total population of 2 million. This means that the incidence rate of lung cancer in Madison is 0.7 or 700 cases per 100,000 people (14,000 [incidence] divided by 2 million [population]).

Relative risk—This is a ratio of risk between two populations or groups. A value of 1.0 means that there is no difference in the risks of cancer in two groups, while a value above 1.0 means that there is a higher risk in one group. For example, in the neighboring city of Jefferson, the incidence rate of lung cancer is only 300 per 100,000 people. Therefore, the people in Madison (with a lung cancer incidence rate of 700 per 100,000) have a relative risk of lung cancer that is 2.3 times higher than those living in Jefferson.

1.1.1. CANCER INCIDENCE IN THE UNITED STATES

Almost everyone has a relative or friend who has developed cancer. A glance at the 2011 cancer rates in Table 1.1 explains why: cancer is a very common disease. In the United States, lifetime cancer risks are 1 in 3 for women and 1 in 2 for men. Nearly 1.6 million new cases were diagnosed in 2011, and this number seems to increase each year.

TABLE 1.1. PROBABILITY THAT MEN AND WOMEN IN THE UNITED STATES WILL DEVELOP CANCER OVER THEIR LIFETIME

Source: American Cancer Society (2011, p. 14).

Excludes nonmelanoma skin cancer.

Cancer types and rates differ for men and women. In the United States, the leading sites of cancer in 2011 were prostate cancer for men (see Table 1.2) and breast cancer for women (see Table 1.3). For both sexes, lung cancer ranks second and colorectal cancer ranks third.

TABLE 1.2. MOST COMMON FORMS OF CANCER FOR MEN IN THE UNITED STATES: 2011 ESTIMATES

Source: American Cancer Society (2011, p. 10).

TABLE 1.3. MOST COMMON FORMS OF CANCER FOR WOMEN IN THE UNITED STATES: 2011 ESTIMATES

Source: American Cancer Society (2011, p. 10).

In general, cancer risk increases with age, with the highest incidence occurring in people over age 65. Childhood cancers are relatively rare and account for less than 1% of all new cancer diagnoses. By far the most common childhood cancer is acute leukemia, which accounts for 34% of all pediatric cancers. See Table 1.4 for a listing of the most frequent forms of childhood cancer.

TABLE 1.4. CANCER INCIDENCE AND MORTALITY STATISTICS FOR CHILDREN AGED 19 YEARS AND YOUNGER

Source: National Cancer Institute SEER Cancer Statistics Review, 1975–2003, 2006.

Rates are per 100,000 and are age-adjusted to the 2000 US standard population.

In each major ethnic group, prostate and breast cancers are by far the most common forms of malignancy. However, as shown by the cancer statistics from 2006, the incidence rates of these two cancers varied per ethnic group. (See Fig. 1.1.) African Americans have the highest overall cancer rates, while Native Americans (including Alaskan Natives) have the lowest cancer rates.

FIGURE 1.1. A comparison of the U.S. incidence rates for prostate cancer and breast cancer across five different ethnic groups. *Female only; **Per 100,000, age adjusted. W = Whites; B = African Americans; H = Hispanics; A = Asians and Pacific Islanders; I = American Indians and Alaskan Natives.

Source: American Cancer Society (2006, p. 32).

Cancer incidence rates also vary per geographic region. The states with the highest cancer incidence rates in 2011 (between 40,000 and 163,000 new cases) were California, Florida, Georgia, Illinois, Michigan, New Jersey, New York, North Carolina, Ohio, Pennsylvania, and Texas. The states with the lowest overall cancer rates in 2011 were Alaska, District of Columbia, North Dakota, Vermont, and Wyoming.

1.1.2. CANCER-RELATED MORTALITY AND SURVIVAL IN THE UNITED STATES

As shown in Table 1.5, cancer remains one of the leading causes of death in the United States (behind heart disease). Despite the relative rarity of cancer in children, it is one of the most common causes of death in this age group as well. Table 1.4 provides the cancer mortality rates for specific childhood cancers. For adults aged 25–44, deaths from cancer are more frequent than any other diseases, but rank below accidents and violent deaths (homicides and suicides).

TABLE 1.5. TEN LEADING CAUSES OF DEATH FOR TWO SPECIFIC AGE GROUPS AND FOR ALL AGES (IN DECREASING ORDER OF FREQUENCY)

Source: National Vital Statistics, Estimated Rates for 2004, Reports Vol. 54 (19).

COPD, chronic obstructive pulmonary disease.

It is encouraging to note that over the past two decades, more people are surviving their cancer diagnoses. The upward trend in cancer survival rates is partially due to the ability to detect cancers at earlier, more treatable stages. The greatest declines in mortality rates have been among women and individuals less than 65 years old. Specific mortality rates depend upon the site of cancer, how advanced the cancer is at diagnosis, and how amenable the cancer is to treatment. As shown in Table 1.6, the highest number of cancer deaths in 2011 were from lung cancer, followed by prostate cancer in men and breast cancer in women.

TABLE 1.6. U.S. CANCER MORTALITY RATES BY SITE AND GENDER: 2011 ESTIMATES

Source: American Cancer Society (2011, p. 10).

One commonly used marker in oncology is the 5-year relative survival rate. This refers to the likelihood that a cancer patient will be alive (with or without disease) 5 years postdiagnosis, after adjusting for normal life expectancy. It is estimated that the overall 5-year survival rate for cancer is 68%. Because of this, genetic counselors will increasingly encounter clients who have personal histories of cancer. In fact, over 11 million Americans are cancer survivors and this figure continues to rise.

Table 1.7 lists the 1999–2006 5-year survival rates for specific cancers. Skin melanoma and breast, prostate, testis, and thyroid cancers had greater than 90% survival rates, while the survival rates for esophageal, liver/bile duct, lung/bronchus, and pancreatic cancer were less than 20%.

TABLE 1.7. THE 5-YEAR RELATIVE SURVIVAL RATES FOR SELECTED CANCERS

Source: American Cancer Society (2006, p. 17).

Rates are adjusted for normal life expectancy and are based on cases diagnosed between 1995 and 2001, followed through 2002.

Cancer survival rates also differ among ethnic groups. African American men have the highest rates of cancer deaths and Asian women have the lowest rates. Table 1.8 compares 5-year survival rates for Caucasian Americans with African Americans, which reveals that African Americans have poorer survival rates for almost all of the common cancers. Despite tremendous advances in cancer detection, prevention, and treatment, there remains a wide gap in the accessibility and uptake of services within certain population groups. Rather than focusing on ethnicity or race, many sociologists argue that the most important determinant of cancer risk is poverty, which is linked with inadequate health insurance, limited access to medical services, and an increased prevalence of known risk factors.

TABLE 1.8. A COMPARISON OF THE 5-YEAR RELATIVE SURVIVAL RATES* (%) BY RACE IN THE UNITED STATES FOR TWO PERIODS OF TIME: 1975–1977 AND 1999–2006

Source: American Cancer Society (2011, p. 18).

* Survival rates are adjusted for normal life expectancy and are based on cases diagnosed in the SEER 9 areas from 1975 to 1977 and 1999 to 2006, and followed through 2007.

1.1.3. GLOBAL INCIDENCE OF CANCER

Over 11 million new cases of cancer were diagnosed worldwide in 2008. The World Health Organization predicts that this figure could increase to over 15 million annual new cases of cancer by the year 2020. Table 1.9 lists the most common cancers diagnosed throughout the world in 2008. Lung cancer topped the list, accounting for approximately 1.6 million new cases and 1.4 million deaths. For men worldwide, the most common forms of cancer in 2008 were lung and bronchus cancer, prostate cancer, and colorectal cancer. For women worldwide, the most common cancers in 2008 were breast cancer, colorectal cancer, and cervical cancer. The cancers with the highest mortality rates around the world were lung/bronchus, liver, stomach, colon/rectum, and esophageal cancers for men and breast, lung and bronchus, colon/rectum, cervix uteri, and stomach cancers for women.

TABLE 1.9. MOST COMMON FORMS OF CANCER FOR MEN AND WOMEN WORLDWIDE

Source: Jemal et al. (2011).

The risk of being diagnosed with cancer was highest in Australia, followed by North America and European countries. The countries with the lowest cancer rates were Afghanistan, Egypt, and India. (See Table 1.10.) Table 1.11 lists the countries with the highest cancer mortality rates.

TABLE 1.10. COUNTRIES WITH THE HIGHEST AND LOWEST INCIDENCE RATES OF CANCER

Source: Mackay et al. (2006).

a 15% and higher risk of getting cancer before age 65.

b 5–7.4% risk of getting cancer before age 65.

TABLE 1.11. COUNTRIES WITH THE HIGHEST CANCER MORTALITY RATES

Source: Organization for Economic Cooperation and Development (OECD) 2004. Health Statistics: Death from cancer by country. http://www.nationmaster.com/graph/hea_dea_fro_can–health–death–from–cancer.

a Per 100,000 for the year 2000.

Industrialized countries tend to have higher rates of cancer than developing countries, because cancer, for the most part, is a disease of old age. A comparison of the most common causes of death for industrialized and developing countries is shown in Table 1.12. Although people in developing countries have a greater chance of dying from an infectious disease than their counterparts in developed countries, cancer has become a major public health concern for all nations. In fact, the World Health Organization estimates that more than 70% of all cancer deaths in 2008 occurred in low- and middle-income countries. This is because developing countries have fewer resources for cancer detection and treatment and the types of cancer that occur (e.g., lung, stomach, liver, and esophageal) tend to be more difficult to treat.

TABLE 1.12. LEADING CAUSES OF DEATH IN LOW INDUSTRIALIZED AND DEVELOPING COUNTRIES (IN DECREASING ORDER OF FREQUENCY)

Source: Lopez et al. (2006).

COPD, chronic obstructive pulmonary disease.

It is important to be aware of the specific population rates of cancer when considering the likelihood of an inherited etiology. For example, the occurrence of breast cancer in three female relatives living in Japan or China is much more striking than three affected relatives in the United States or Canada. Conversely, a family history of gastric cancer, while rare in North America, is much more commonplace in Asia.

1.2. CANCER ETIOLOGY

In 1883, Sir Percival Potts in London noted that young boys who worked as chimney sweeps developed scrotal cancer at higher than usual rates. This was the first documented report linking an environmental exposure to cancer development. More than a century later, numerous factors in our environment are known or suspected to cause cancer.

In the majority of cases, it is a combination of factors that leads to cancer development. At this time, the interaction between genetic and environmental risk factors remains poorly understood. For example, the extent to which lifestyle changes can modify the cancer risk in individuals with inherited predispositions to cancer is unclear.

Hereditary factors are the primary underlying source of cancer in only a small percentage of cases. About 65% of cancers are thought to be due to either dietary factors or tobacco exposure (see Table 1.13). Other factors are also important contributors in the occurrence of specific malignancies. To calculate a client’s cancer risk, genetic counselors may need to consider nonhereditary factors, such as lifestyle, medical conditions, occupational exposures, ethnicity, and geographic region.

TABLE 1.13. THE ESTIMATED AMOUNT OF CANCER CASES ATTRIBUTED TO SPECIFIC RISK FACTORS

Source: Offit (1998, p. 34).

1.2.1. NONMODIFIABLE RISK FACTORS

Everyone is at risk for developing cancer at some point in their lives and the most significant risk factors are, for the most part, beyond our control. Table 1.14 lists the major nonmodifiable risk factors described below.

TABLE 1.14. MAJOR MODIFIABLE AND NONMODIFIABLE CANCER RISK FACTORS

Source: Mackay et al. (2006), American Cancer Society, The Cancer Atlas, pp. 24–25.

1.2.1.1. Aging

Age is probably the most significant predictor of cancer risk, with people over age 65 having the highest risks. This is likely due to the aging process, which results in increased genetic errors during cell mitosis and a less effective immune response.

1.2.1.2. Ethnicity or Race

Rates of specific cancers vary substantially by ethnic group. For example, melanoma and other cutaneous skin cancers are highest in fair-skinned people of European origin and lowest in dark-skinned people of African origin. According to Judith Mackay and colleagues, the rate of skin melanoma in Australia (with a predominance of English descendents) is 51 in 100,000 compared with 2 in 100,000 in Zimbabwe, which also lies near the equator, but has mainly African descendents (2006, p. 36).

1.2.1.3. Heredity

It is estimated that 5–10% of cancers are due to an inherited gene mutation or deletion. However, a much higher proportion of cancers (perhaps 30–40%) may be due to moderately penetrant cancer susceptibility genes coupled with exposures to carcinogens.

1.2.1.4. Gender

Cancer risks are typically higher in men than in women. Drs. Zahm and Fraumeni (1995) postulate that the higher rates of cancer in men might be explained by their higher rates of tobacco and alcohol use, which are linked with a variety of malignancies. Exceptions are thyroid cancer and gallbladder cancer, both of which occur more frequently in women, which suggest hormonal triggers.

1.2.1.5. Chronic Medical Conditions

Some chronic diseases or medical conditions can, over time, lead to certain forms of cancer. One such condition is colitis, which is a series of inflammations in the colon that is associated with a 30% lifetime risk of colorectal cancer. There are also conditions which can be triggered by the same mechanisms that lead to malignancy, such as the increased rate of diabetes in families with familial pancreatic cancer.

1.2.1.6. Chromosomal Anomalies

Individuals with Down syndrome (trisomy 21), Klinefelter syndrome, and Turner syndrome have increased risks for developing specific forms of cancer. Children with Down syndrome have a 10–20-fold increased risk to develop acute lymphoblastic leukemia (ALL) as well as an increased risk of acute myeloid leukemia and a rare form of leukemia termed acute megakaryocytic leukemia. Males with Klinefelter syndrome (47, XXY) are known to be at higher risk of breast cancer and extragonadal germ cell tumors and they may also have higher risks of non-Hodgkin lymphoma and lung cancer. Females with Turner syndrome (45, X0) are at increased risk for developing Wilms’ tumor, leukemia, gonadal tumors, neurogenic tumors, and if they take unopposed estrogen, uterine cancer.

1.2.2. MODIFIABLE RISK FACTORS

Carcinogens are identified on the basis of epidemiology studies or by testing in animals. The term carcinogen refers to an exposure that can increase the incidence of malignant tumors. Carcinogens rarely cause cancer at all times under all circumstances. For example, spending a few weeks painting the exterior of your house does not increase your risk of cancer; in contrast, professional house painters are at a decidedly increased risk of cancer due to chronic exposures to airborne carcinogens. The actual level of cancer risk depends on the carcinogenic potential of the agent as well as the intensity and duration of the exposure. Figure 1.2 illustrates the variety of carcinogenic potential in animal studies based on the amount and timing of specific exposures.

FIGURE 1.2. Outcome of various sequences of experimental exposure to initiating agents and promoting agents in mouse skin.

Source: Okey et al. (2005, p. 27). Reproduced with permission from McGraw-Hill.

The study of potential carcinogens in humans is hampered by many inherent difficulties. Allan Okey et al. (2005) list the following challenges to identifying human carcinogens:

The time interval between exposure to a potentially carcinogenic agent and the detection of a tumor may be 10–20 years. The long latency period in humans makes it difficult to link tumors with particular exposures.

It is often difficult to quantify the level of exposures to specific agents, especially if it has occurred many years earlier. Most exposures do not leave any long-term traces of contamination with which to measure.

Humans are exposed to a variety of chemicals and other agents over their lifetime. These complex exposures may influence the carcinogenic effects and can confound attempts to attribute a tumor to a particular agent.

People may have very different susceptibilities to cancer despite similar exposures. This may make it difficult to ascertain the true carcinogenicity of a particular agent.

Proving statistical causality requires an extremely large population group unless the agent has an extraordinarily high tumor potential. Establishing causality of agents that have low or moderate carcinogenic potential will be more difficult.

The United States-based National Toxicology Agency and the International Agency for Research on Cancer (IARC) both publish annual lists of known and suspected human carcinogens. The major cancer-causing agents are presented in the succeeding sections.

1.2.2.1. Tobacco Use

It is estimated that one in five cancer deaths are caused by cigarettes, cigars, and smokeless tobacco (chewing tobacco or snuff). Tobacco smoke contains about 4000 substances, more than 50 of which are known or suspected to cause cancer in humans. Secondhand exposure to tobacco, termed passive smoking, has also been determined to be carcinogenic. Acute myeloid leukemias and malignancies in the following organs have been directly linked to tobacco use: nasopharynx, nasal cavity and paranasal sinuses, lip, pharynx, uterus, cervix, kidney, lung, larynx, oral cavity, esophagus, bladder, stomach, and pancreas. The American Cancer Society estimates that a staggering 80% of lung cancers in men and 50% of lung cancers in women are directly related to tobacco exposure.

1.2.2.2. Alcohol Use

Heavy use of alcohol is linked to increased rates of cancer in the oral cavity, esophagus, colon, liver, and upper respiratory tract. Moderate use of alcohol is associated with an increased risk of breast cancer.

1.2.2.3. Unhealthy Diet

It is estimated that 30% of cancers in developed countries are due to a Western diet, that is, a diet that is high in saturated fats and low in fruits and vegetables. The Western diet increases the risk of breast, colon, prostate, and esophageal cancers. In developing countries, salt-preserved foods can cause stomach cancer, Chinese-style salted fish can cause nasopharynx cancer, and repetitive ingestion of very hot drinks and food can cause cancers of the oral cavity, pharynx, and esophagus.

1.2.2.4. Obesity

Obesity is a significant cancer risk factor in developed countries and is linked to an unhealthy diet and physical inactivity (a triad known as the Western lifestyle). Obesity, defined as a body mass index (BMI) over 30.0, has been associated with an increased risk of endometrial, kidney, gallbladder, and breast cancers.

1.2.2.5. Physical Inactivity

A sedentary lifestyle is associated with an increased risk of colon cancer. In women, a lack of exercise may also increase the risk of breast cancer.

1.2.2.6. Infectious Agents

About 18% of cancers worldwide are caused by an infectious agent. In developing countries, approximately one in four cancers are caused by a bacterial, viral, or parasitic infection. Table 1.15 provides a list of the most common infectious agents that cause specific types of cancer. The most significant infectious agents are Helicobacter pylori (stomach cancer), human papillomaviruses (cervical cancer), and the hepatitis B and C viruses (liver cancer).

TABLE 1.15. INFECTIOUS AGENTS KNOWN OR SUSPECTED TO BE CARCINOGENIC TO HUMANS

Source: National Toxicology Program, Department of Health and Human Services (2011).

1.2.2.7. Ultraviolet Radiation

The main source of ultraviolet radiation is sunlight, although another source is radon, which is a gas produced from decaying uranium. Levels of radon, which is naturally emitted from rocks and soil, vary greatly around the globe. For urban dwellers, radon levels are generally highest in the basement and are often associated with poor ventilation. Long-term exposures to sunlight and other forms of ultraviolet radiation (including sunlamps and tanning beds) increase the risks of skin, lip, and lung cancer. The risk of skin cancer is higher in people with pale skin and/or if exposure occurs in childhood.

1.2.2.8. Ionizing Radiation

Excessive exposure to ionizing radiation, such as repeated X-rays and radiation therapy, is associated with increased rates of leukemia, bone cancer, and other solid tumors. (See Section 2.3.2 for more information about radiation therapy.)

1.2.2.9. Occupational Exposures

Between 2% and 4% of cancer cases are attributed to occupational exposures (see Table 1.16). Exposures to carcinogenic particles and gases can lead to a variety of cancer types, although lung cancer is the most common. Many of these carcinogens require moderate to high levels of exposure over a specified length of time. Exposures to carcinogens occur in a variety of jobs, from X-ray technicians to dry cleaners. Two of the most hazardous professions in terms of cancer risks are manufacturing and mining:

Manufacturing—Factory workers can be exposed to a variety of carcinogenic agents, usually airborne. For example, workers in the dye industry are exposed to aromatic amines, benzidine, and napthylamine, and therefore have higher risks of mesothelioma and cancers of the lung, nasal passages, and sinuses. Manufacturers of shoes, hardwood floors, and furniture have documented increased risks of cancer, particularly lung cancer.

Mining—Miners are continually exposed to air that is chock-full of minerals and dust. This can include arsenic, radon, polycylic hydrocarbons, and hematite. Miners are at increased risk for developing lymphoma and cancer of the skin, lung, liver, and nasal sinus.

TABLE 1.16. OCCUPATIONAL AND EXPOSURE CIRCUMSTANCES KNOWN OR SUSPECTED TO BE CARCINOGENIC TO HUMANS

Source: National Toxicology Program, Department of Health and Human Services (2011).

1.2.2.10. Environmental Pollution

About 1–4% of cancer cases are caused by pollution of the air, water, and soil. This is a more serious problem in urbanized countries than in developing countries.

1.2.2.11. Medicinal Drugs

In the 1950s, expectant mothers were given a new drug called diethylstilbestrol (DES) to prevent miscarriage. Twenty years later, it was recognized that women exposed to DES in the womb (so-called DES daughters) have higher rates of vaginal and cervical cancers. Estrogen is a key ingredient in birth control pills and hormone replacement therapy, but is associated with increased risks of both endometrial and breast cancer. Certain medications may also be carcinogenic. For example, alkylating agents, which are used for chemotherapy, can lead to increased risks of leukemia. (See Chapter 2, Section 2.3.3.1 for more information about alkylating agents.)

1.2.2.12. Food Contaminants

A small proportion of cancers are due to food contaminants. These contaminants can be naturally occurring, such as aflatoxins, or man made, such as polychlorinated biphenyls (PCBs). Aflatoxins, which are by-products of Aspergillus fungus, are commonly found in grains and legumes and can cause liver cancer. PCBs, which are commercially produced chemical mixtures, seldom degrade fully and are now widespread through the aquatic food chain because of toxic dumping in rivers and oceans prior to 1977. Human ingestion of high levels of PCBs can cause multiple problems, including liver cancer. Other sources of food contaminants are pesticide sprays, bacteria, and food additives.

1.3. CASE EXAMPLES

Case 1: Everyone in my old neighborhood has gotten cancer.

Monica, a counselor with 10 years’ experience in cancer genetics, greeted her first client of the afternoon and smiled at the woman’s colorful macaroni necklace, the result of an earlier kindergarten luncheon with her grandson. The woman, Joan Smith, age 67, had recently moved from a small town in Maine to southern Massachusetts to be nearer to her daughter and four grandchildren. In fact, her main motivation for the genetic counseling visit was to clarify their possible risks of cancer.

Joan had been diagnosed with estrogen and progesterone (ER/PR)-positive breast cancer at age 60, 1 year after her twin sister had been diagnosed with ductal carcinoma in situ. Their mother also had breast cancer at age 72, but had recently celebrated her 90th birthday. No one else in this large family had been diagnosed with breast or ovarian cancer. The family was of French Canadian and Irish ancestry.

After completing the family history, Monica explained how frequently breast cancer occurred in the general population and reassured her client that the pattern of breast cancer in her family was unlikely to be indicative of a strong underlying inherited factor (e.g., a BRCA1 or BRCA2 mutation). She then asked Joan if she agreed with this assessment.

Joan (who had an annoying habit of calling everyone dear, but was sweet-natured enough to get away with it) was relieved to learn she didn’t need the genetic test that her doctor had badgered her about. However, she did raise another concern.

Pulling out a well-worn manila envelope, Joan began handing newspaper clippings to the genetic counselor. I’m not concerned about that breast cancer gene, dear, but I am really worried about my family’s risks of cancer because of where we grew up. I saw a movie once where this factory dumped chemicals into a nearby river and people got cancer from drinking contaminated water. Did you see the film? She looked expectantly at the genetic counselor, who admitted that she had seen the film Erin Brokovich.

Well dear, that got me worrying about my family, because everyone in my old neighborhood has gotten cancer! First, there’s the neighbor in the house next door to me on the left who died from prostate cancer—here is his obituary. And then the next-door neighbor on my right got lung cancer—here is her obituary. Two doors down from us, Mr. Smith and his wife both had colon cancer a few years back; he died but she didn’t. In the house on the corner, the family had a son who died from a brain tumor in his thirties; they had moved away by then but he had grown up in the neighborhood. The neighbors across the street lost a daughter to breast cancer and I recently learned that one of their sons has testicular cancer—or is it prostate cancer?—in his fifties. Then there are the breast cancer cases in our family. Isn’t that a lot of cancer on one street?!

Monica looked down at the stack of newspaper clippings sitting in her lap, then up at Joan’s anxious face. She agreed that a lot of cancer had occurred on her street, but gently reminded her that collectively, cancer was a common disease. She reviewed the family history with Joan, noting that the cancers were varied, with most cases occurring over the age of 50. In addition, the one paper mill in the client’s town had not been active for several decades.

Monica explained that exposures to carcinogens, such as contaminated drinking water, often caused clusters of similar types of cancer at younger than usual ages. The genetic counselor then said that she did not think the pattern of cancer in Joan’s old neighborhood represented a true cancer cluster, but said she understood why the client had been concerned. Monica also encouraged the client to contact the Department of Public Health in Maine if she felt the situation warranted further scrutiny. Joan said that the conversation was a load off her mind and decided not to pursue it further.

Case 1 wrap-up: This case describes genetic counseling strategies for dealing with a possible (albeit unlikely) environmental cluster of cancer.

Case 2: Yes, I know why people in my family get cancer. It’s from the [fill in the blank].

Deena, a recent genetic counseling graduate in her first job, still found it intimidating to provide group counseling, but allowed herself a brief moment of satisfaction at how smoothly the session was going. She had just finished collecting an extensive family history that cataloged four generations of breast and ovarian cancer in the Riske family. The three adult sisters, their mother, and a maternal aunt had all chimed in with information, which made it a chaotic process, but had allowed the counselor to see them interact together. The mother had undergone radical mastectomies in her thirties because of bilateral breast cancer and was the best candidate for testing, but all of the women seemed eager to gain control over the disease that had claimed so many of their relatives.

As a way of transitioning the discussion to genetic testing, Deena asked her clients if they knew why so many female relatives had developed cancer. Anticipating the response that cancer was clearly running through their family, the counselor began mentally preparing her mini lecture on the BRCA1/2 genes and logistics of testing. The mother’s answer was so unexpected, Deena asked her to repeat it, wondering if she had heard her correctly.

Yes, I know why people in my family get cancer. It’s from the cheese, said the mother emphatically. The other women in the family all nodded in agreement.

The cheese…? asked the genetic counselor in a puzzled voice.

My family is originally from Wisconsin and they were dairy farmers. They ate a lot of cheese. All kinds of cheese—Gouda, cheddar, Edam, Brie, Monterey Jack. My sisters and I grew up eating cheese with every meal and I admit that I also fed my kids a lot of cheese.

We all did, interjected the maternal aunt with a nod. Good for growing bones, that’s what we were always told.

One of the sisters leaned forward and asked, Maybe the type of cheese makes a difference; remember that Aunt Louise only ate cheddar. The family immediately began going through the family tree cataloging the average daily consumption of cheese (and which types) each female relative had eaten prior to developing cancer.

Unsure of how to steer the conversation back to genetics without seeming rude, Deena waited until there was a lull in the conversation.

Anyway I’ve told my daughters to limit how much cheese they eat, but is there anything else they should be doing? concluded the mother.

Deena saw her opening and grabbed it. You know, it’s hard to point to one risk factor and say with certainty that it’s the culprit, it’s the cause of cancer. In general, breast cancer and ovarian cancers are caused by a combination of factors. It could be that your family has more than one risk factor. The factor that increases breast and ovarian cancer risk by the greatest amount is not diet, but rather family history or genetic susceptibility.

Deena went on to discuss the BRCA1 and BRCA2 genes. She’d never convince the family that the cheese consumption did not partially cause their cancers, but did get them to realize they might also have an inherited risk.

Case 2 wrap-up: This case describes ways to discuss inherited factors while being respectful of the family’s theories for why cancer occurred.

1.4. FURTHER READING

American Cancer Society. 2006. Cancer Facts & Figures 2006. American Cancer Society, Atlanta, GA. http://www.cancer.org/Research/CancerFactsFigures/CancerFactsFigures/cancer-facts-figures-2006.

American Cancer Society. 2011. Cancer Facts & Figures 2011. American Cancer Society, Atlanta, GA. http://www.cancer.org/Research/CancerFactsFigures/CancerFactsFigures/cancer-facts-figures-2011.

Gould, SJ. 2004. The median isn’t the message. Ceylon Med J 49:139–140.

Jemal, A, Bray, F, Center, MM, et al. 2011. Global cancer statistics. CA: A Cancer Journal for Clinicians 61:69–90.

Lopez, AD, Mathers, CD, Ezzati, M, et al. 2006. Systematic analysis of population health data. Lancet 367:1747–1757.

Mackay, J, Jemal, A, Lee, NC, and Parkin, DM. 2006. The Cancer Atlas. American Cancer Society, Atlanta, GA.

McLaughlin, J, and Gallinger, S. 2005. Cancer epidemiology. In Tannock, I, Hill, RP, Bristow, RG, and Harrington, L (eds), The Basic Science of Oncology, 4th edition. McGraw-Hill Co, New York, 4–24.

Minino, AM, Heron, MP, and Smith, BL (eds). 2006. Deaths: Preliminary Data for 2004. National Vital Statistics Report. National Center for Health Statistics. Hyattsville, MD, vol. 54, no. 19.

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CHAPTER 2

Cancer Detection and Treatment

We must stop speaking of cancer in whispers, as if it is something shameful. For when it is brought out into the brilliant light of day it seems to shrink, to pull back, to diminish. Above all, know this: Cancer is a beatable, treatable, survivable disease.

(Girard, 2004, p. 3)

A cancer genetic counseling session often begins with hearing the client’s cancer story: the symptoms that led to the suspicion of cancer, the way in which the diagnosis was made, and the subsequent treatment regimen. This chapter describes the process of making a cancer diagnosis, the system used to classify tumors, and the current strategies for cancer treatment.

2.1. THE DIAGNOSIS OF CANCER

This section provides the information necessary to understanding a cancer diagnosis, from how cancer is diagnosed to the nomenclature used to describe the tumor.

2.1.1. CANCER DETECTION

A diagnosis of cancer often begins with a worrisome symptom or problem on a medical intake or screening test. For example, a physical exam may reveal swollen lymph glands or unusual tenderness. A routine screening test, such as a colonoscopy, cervical Pap smear, or blood test, may identify the presence of atypical cells or an unusually high number of cells. For example, a blood specimen that shows a dramatically high count of blasts (immature white blood cells) in a young child may point to the presence of acute lymphoblastic leukemia.

In many cases, the patients have noticed warning signs of cancer (see Table 2.1). They may note a new worrisome physical finding, such as a breast lump or they have health problems that are not abating over time (such as a persistent cough) or even getting worse (such as gastrointestinal upset).

TABLE 2.1. COMMON WARNING SIGNS OF CANCER

Source: American Cancer Society (2010).

People are more likely to experience symptoms or warning signs if their tumor:

is pressing on neighboring tissue and causes pain

is interfering with the functioning of normal tissue

has invaded the blood vessels to cause abnormal bleeding

has grown large enough to be seen or palpated

A malignant tumor can be present for months, even years, before it is detected. The reasons why cancer detection can be so difficult are presented in the succeeding sections.

2.1.1.1. Lack of Warning Signs

There may be no physical symptoms that signal the presence of early-stage cancer. Observable signs of cancer are more likely to be noticed as the cancer progresses. Unfortunately, this means that the hallmarks of cancer, such as a lump, bleeding, or pain, often indicate a malignancy that is already in an intermediate or advanced stage.

2.1.1.2. Imperfect Screening Methods

To be effective, screening tests need to be easily performed, affordable, and accurate in detecting disease cases while limiting the number of falsely positive tests. The cancers must be detectable at early (more curable) stages and must occur at a frequency that justifies population screening. For example, the Pap smear is an effective screening test for cervical cancer, because it is a fairly common disease and early diagnosis has been shown to make a significant difference in survival. In contrast, it is no longer recommended that smokers obtain annual chest X-rays because detecting lung tumors by X-ray rather than waiting until symptoms develop does not seem to alter lung cancer mortality rates. Screening tests for less common forms of cancer, such as retinoblastoma, are offered only to children known to be at high risk, both because it is a rare disease and screening occurs under general anesthesia, which carries its own risks.

2.1.1.3. Elusive Premalignant Cells

Few organs can be readily and repeatedly sampled, which makes it difficult to monitor the organs for malignant or (even better) premalignant cells. At this point, only a few screening tests reliably detect premalignant cells, with the Pap smear (which identifies abnormal cells of the cervix) being one of the best examples.

2.1.2. MAKING THE DIAGNOSIS OF CANCER

The workup for cancer typically begins when other more likely explanations have been ruled out. For example, the differential diagnosis of frequent headaches includes vision problems, allergies, and stress. More serious possibilities, such as a brain tumor or neurological problem, are less likely to be entertained at the outset because of their relative rarity. Unfortunately, a common complaint among members of families with hereditary cancer syndromes is that signs of cancer were initially ignored or downplayed by their providers.

The method by which the cancer will be identified depends on the tumor type (see Table 2.2). The presence of cancer may be suggested by physical exam, imaging studies, specialized blood tests (tumor markers, chromosome studies), or invasive procedures. Biopsy is required to make a definitive diagnosis. For example, the diagnosis of renal cell carcinoma may start with an abnormal urine test and an ultrasound of the kidneys, but it is the biopsy and subsequent pathologic analysis that will make the diagnosis.

TABLE 2.2. EXAMPLES OF MEDICAL TESTS THAT CAN LOOK FOR EVIDENCE OF CANCER

Source: Dollinger et al. (2002).

Tumor marker tests look for the presence of proteins in the bloodstream that can be produced by specific tumors. (See Table 2.3.) The higher the level of proteins detected, the more worrisome it is that the person might have an active tumor. A few of the tumor marker tests are accurate enough to be used for screening, such as the alpha-fetoprotein (AFP) test for liver cancer. However, tumor markers are mainly used to look for evidence of recurrent disease.

TABLE 2.3. A LIST OF COMMONLY ORDERED TUMOR MARKERS

Source: Dollinger et al. (2002).

Individuals will be referred to a medical oncologist either when the suspicion of cancer has been raised or following the initial diagnosis. As with most medical specialties, clinical oncology is divided into many subspecialties. Other members of the cancer care team include surgeons, radiologists, radiation oncologists, pathologists, and mental health professionals; the care of individuals with cancer requires a multidisciplinary team.

Cancer can be a high-burden disease on both patients and their families. Learning that one has cancer can engender feelings of shock, anger, intense sadness, and extreme anxiety. As patients enter cancer treatment, they often need to make major adjustments in terms of their family responsibilities and workload. At many cancer centers, patients and their families have the opportunity to meet with a social worker or psychologist. Patient support groups may also be helpful.

2.1.3. CANCER TERMINOLOGY

It is not naming as such that is pejorative or damning, but the name cancer. As long as a particular disease is treated as an evil, invincible predator, not just a disease, most people with cancer will indeed be demoralized by learning what disease they have. The solution is hardly to stop telling cancer patients the truth, but to rectify the conception of the disease, to de-mythicize it.

(Sontag, 1977, p. 7)

Hippocrates named the hard gray tumor tissue that extends into normal tissue Carcinoma for its crablike appearance. The Latin word for crab is cancer, which continues to be used to describe all carcinomas and melanomas.

The terminology used to describe specific tumors can be daunting and it may be helpful to consider how these names are derived. Tumor nomenclature provides information about where in the body and in what type of tissue and cell the cancer originated.

2.1.3.1. Site of Origin

The medical term for a tumor is a neoplasm, which literally means new growth. Neoplasms can develop in almost every tissue of the body. The name of a neoplasm will first indicate the site in the body where the tumor has originated. As examples, a hepatocellular carcinoma is a liver cancer and a rhabdomyosarcoma is a tumor of the striated muscle.

2.1.3.2. Tissue Type

The rationale underlying the name and classification of tumors can be found in embryology (see Table 2.4). In the early embryo there are three layers of germ cells termed the ectoderm, the mesoderm, and the endoderm.

Ectoderm—The ectoderm forms the outer layer of cells that comprise the skin and nervous