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2003 Meet the Expert: Getting Ahead of the Curve: New Strategies in Cancer Prevention and Screening
Introduction
Cancer Advances
Information From the Experts
New York – April 2003
Getting Ahead of the Curve: New Strategies in Cancer Prevention and Screening
As the leading society of medical professionals who treat people with cancer, the American Society of Clinical Oncology (ASCO) is committed to improving cancer care and prevention. As part of this mission, ASCO has developed patient resources, such as the Cancer Advances series, to help consumers become better educated about various aspects of cancer including its prevention, screening, diagnosis, treatment, and care.
This issue of Cancer Advances focuses specifically on cancer risk, prevention, and screening. Over the past several decades, much progress has been made in understanding the causes of cancer, as well as our ability to screen for various types of cancer.
For instance, we now know that the risk of developing cancer can be greatly reduced by avoiding certain things that are known to cause cancer, such as smoking, second-hand smoke, and overexposure to the sun. We also know that other factors, such as good nutrition and regular exercise, help lower the risk of many different cancers.
Regardless of the type of cancer, it is clear that early detection of the disease is key to improved survival. Screening—including going for regular check-ups, performing self exams, and following guidelines for additional screening tests, such as mammography and colonoscopy—is essential to early detection.
The following is a look at five specific types of cancer, and an overview of the various prevention and screening methods that are currently available for each. In addition, each section features a look ahead to some of the new techniques that are being studied as possible prevention and screening methods for the future.
The information contained in this publication is based on expert presentations from the ASCO Meet the Experts session held in New York in April 2003. This information is not intended as medical advice or as a substitute for the treating physician's own professional judgment; nor does it imply ASCO endorsement of any product or company.
Colorectal Cancer
Colorectal cancer is the second most common cancer and third leading cause of cancer death in the United States. In 2003 alone, it is estimated that colorectal cancer will kill approximately 57,000 Americans. However, when colorectal cancer is detected early, it can often be cured.
Colorectal cancer is a disease in which normal, healthy cells in the colon or rectum begin to grow uncontrollably. If these cells are not treated or removed, they may eventually form a growth or tumor.
Colorectal cancer can begin in either the colon or the rectum. The vast majority of colorectal cancers begin as polyps. Polyps are non-cancerous growths that may occur on the inner wall of the colon and rectum as people get older. "The best way to prevent colorectal cancer is to detect and remove polyps before they become cancerous," said Bernard Levin, MD, Chair of ASCO's Cancer Prevention Committee and Vice President for Cancer Prevention at The University of Texas M.D. Anderson Cancer Center.
Risk and Prevention
While the exact cause of colorectal cancer is unknown, certain risk factors appear to increase a person's risk of developing the disease. Some risk factors can be controlled, such as smoking or physical inactivity. Other risk factors, such as a person's age, cannot be changed.
"People at average risk for colorectal cancer have no known risk factors other than age," explained Dr. Levin.
People who have a personal or family history of colorectal polyps, colorectal cancer, or inflammatory bowel disease have a higher risk of developing colorectal cancer. These people are advised to have a colonoscopy every five years beginning at the age of 40.
People can lower their risk of developing colorectal cancer by managing certain risk factors. For instance, a high-fiber, low-fat diet may reduce colorectal cancer risk. It is important to eat plenty of fruits, vegetables, and whole grain foods. Increasing physical activity and maintaining a healthy body weight can lower risk of colorectal cancer as well.
In addition, chemoprevention—the use of natural and man-made substances to prevent the onset of cancer—may play a role in preventing colorectal cancer. The following therapies are currently being studied for the prevention of colorectal cancer: - Many studies suggest that the regular use of nonsteroidal anti-inflammatory agents (NSAIDS), such as aspirin, may reduce the development of colorectal polyps in people at high risk for colorectal cancer. NSAIDs appear to protect against cancer by blocking COX-2 enzymes, which play a role in cancer growth.
- Some studies suggest that increasing calcium intake by taking supplements or consuming low-fat dairy products will lower risk of colorectal cancer in people who have already been diagnosed with polyps.
- Vitamin D and folic acid, naturally occurring substances, may also protect against colorectal cancer.
- A decreased risk of colorectal cancer has been associated with postmenopausal estrogen replacement therapy, with or without the hormone progesterone. However, this association requires further study, especially given the fact that recent research suggests that hormone replacement therapy can cause other health problems.
Screening
Colorectal cancer screening has been shown to save lives by detecting cancer at an early stage, when it is more easily treated and has a better prognosis.
Undergoing colorectal screening tests is recommended for those 50 years of age and older because the incidence of colorectal cancer begins to rise after age 50.
Recommended screening tests for this population include: - An annual fecal occult blood test.
- Flexible sigmoidoscopy every five years, or a colonoscopy every 10 years.
Unfortunately, rates of colorectal cancer screening are poor.
Only about 30% of people in the U.S. take advantage of colorectal cancer screening, according to Dr. Levin. "It's fair to say that if we used some, or all, or any combination of colorectal cancer screening methods, we would be doing far better than we are currently doing."
There are several different methods currently used to screen for colorectal cancer: - A fecal occult blood test (FOBT) looks for hidden blood in the stool, an early sign of colorectal cancer. The test itself is simple to perform, but requires the patient to follow a restricted diet and collect a stool sample for evaluation. Patients often find this unpleasant to do.
- A flexible sigmoidoscopy allows doctors to examine the rectum and the lower portion of the colon. During this test, doctors insert a thin tube with a light and camera at its tip to detect any abnormalities. Patients must prepare for this test by having an enema, following a diet of clear liquids for two days, and taking laxatives.
- A colonoscopy is an examination that is similar to a sigmoidoscopy. However, during a colonoscopy, a doctor uses a longer tube to examine the entire colon. During a colonoscopy, polyps or other growths can be removed. This prevents polyps from progressing to colorectal cancer. Similar to a sigmoidoscopy, patients must prepare for this test by having an enema, following a diet of clear liquids for two days, and taking laxatives.
"Colonoscopy is unique among screening tests in that it is also a therapeutic procedure," said Dr. Levin. "You can remove the polyps that are likely to develop into cancer, and, by doing so, you are extremely likely to prevent cancers from ever developing."
However, there is low compliance in the public despite the effectiveness of colonoscopy. Patients often find the colonoscopy embarrassing or uncomfortable. - A double contrast barium enema (DCBE) is a diagnostic technique in which a liquid substance, called barium sulfate, is introduced into the large bowel. This procedure helps detect abnormalities by outlining the colon and rectum on X-rays. The doctor then takes a series of X-rays of the colon and rectum.
- A virtual colonoscopy is an emerging technique that uses CT scans—scans that capture multiple internal images of the body—and uses a computer to put them together to create a three-dimensional image that can be used to look at the bowel. Virtual colonoscopy, which is also called CT colonography, does not offer the opportunity to remove polyps that might be found during the examination.
"Virtual colonoscopy, in my opinion, is a promising technique. The reasons for this are that we're having faster and faster scanners all the time that have been able to incorporate more data, it reduces the amount of radiation, and it's less invasive," said Dr. Levin.
"Having said all that, I want to stress my own bias at the moment, which is that [virtual CT scans] are not ready for routine use and that the billboard ads that offer CT scans of the body, CT scans of the lungs, CT scans of the heart, or CT scans of the colon, are commercially motivated," added Dr. Levin. "Outside of a trial, it's not ready for primetime use."
Though there are several methods to screen for colon cancer, getting people to use any test at all is a challenge. "Colorectal cancer screening is not something most people like to think about, talk about, and certainly don't practice," said Dr. Levin.
There are many reasons for poor screening rates, but the most common is that many people are embarrassed or uncomfortable with the tests themselves because they are invasive.
"We can debate the merits of these tests and their relative limitations, but what we cannot debate is the fact that they're not being used as much as they should be...we could eliminate probably one half of all deaths due to colorectal cancer if we actually implemented the use of these tests."
It is important to remember that these tests offer the best opportunity to detect colorectal cancer.
Research on the Horizon
New knowledge about the causes of colorectal cancer is helping researchers develop new methods of detection that will benefit patients. Many of these new approaches are based on identifying abnormal genes and proteins that play a role in colorectal cancer. By identifying cancer early, doctors have a better chance of curing colorectal cancer.
Breast Cancer
Breast cancer is the most commonly diagnosed cancer in women in the United States, and is second only to lung cancer in causes of death by disease among women. Men can also develop breast cancer, but male breast cancer is rare, accounting for less than 1% of all breast cancer cases.
If diagnosed at an early stage, breast cancer has a high cure rate. Nearly 97% of women diagnosed with localized breast cancer (breast cancer that has not spread beyond the breast) will live more than five years beyond their diagnosis.
About 90% of all breast cancers occur in the ducts or lobes of the breast. Ducts are narrow, tube-like structures through which breast milk flows. Each breast is made up of 15 to 20 lobes, and within each lobe is one milk duct. Almost 75% of all breast cancers begin in the cells lining the milk ducts. These cancers are called ductal carcinomas. Cancers that begin in the lobes are called lobular carcinomas.
Fortunately, there has been much progress against breast cancer. "Today, there are more breast cancer survivors than ever before because there's been a dramatic decrease in mortality related to breast cancer," said Olufunmilayo I. Olopade, MBBS, Director of the Center for Clinical Cancer Genetics at The University of Chicago Medical Center in Illinois.
In fact, since 1989, the numbers of deaths from the disease have steadily fallen. "As we continue to refine our screening methods to detect breast cancer in its earliest stages, when it's most likely to respond to treatment, we are poised to see an ever greater decline," said Dr. Olopade.
Risk and Prevention
While we still do not know exactly what causes the majority of breast cancers, we do know that certain identifiable risk factors can contribute to breast cancer's development. Women who have these risk factors are more likely to develop breast cancer.
The following factors increase a woman's risk of breast cancer:- In general, breast cancer risk increases with age, with the majority of breast cancers developing in women over the age of 50.
- Breast cancer risk is higher among women whose close blood relatives have or had breast cancer. "A number of epidemiology studies and observational studies suggest that for each breast cancer patient that's diagnosed, about one in three of them will have at least one relative who has had breast cancer," Dr. Olopade explained.
"However, given that breast cancer is very common, and it's a disease of women, you might, in fact, find that in any family there will be one or two women who have had breast cancer. So the question remains, is having a family history of breast cancer equal to a high risk for breast cancer? I think we have to qualify that because of the fact that breast cancer is so common," cautioned Dr. Olopade.
- Women who began menstruating before the age of 12, or who go through menopause after the age of 50, are at higher risk. This is because their breast cells have been exposed to estrogens for relatively longer periods of time. Estrogen has been linked to the development of breast cancer.
- Women who have never had a full-term pregnancy have a higher risk of developing breast cancer. However, pregnancy after the age of 30 increases a woman's risk of developing breast cancer more so than had she not become pregnant at all.
- Women who have been diagnosed with proliferative breast disease, a non-cancerous condition resulting from the overgrowth of cells lining either the ducts or the lobes of the breast, have a slightly higher risk of developing breast cancer. Atypical hyperplasia, a condition of abnormal breast cells, increases a woman's breast cancer risk by four to five times.
- Obesity is associated with an increased risk of developing breast cancer, especially in women after menopause. Having more fat tissue may increase estrogen levels, and therefore increase the likelihood of developing breast cancer.
- Women who as children or young adults have had radiation therapy to the chest area as treatment for another cancer are at a significantly increased risk for breast cancer.
- Many studies have shown that recent use of hormone replacement therapy (HRT), or the long-term use of HRT, may increase a woman's risk of developing breast cancer. However, a woman's breast cancer risk appears to return to normal within five years of discontinuing HRT.
- Mutations to the BRCA1 or BRCA2 genes—abbreviations for "Breast Cancer Gene 1" and "Breast Cancer Gene 2"—are associated with increased breast cancer risk. These mutations are present in about 5% to 10% of women with breast cancer.
"A number of genes have been identified beyond BRCA1 and BRCA2, but none of them really carries as high a contribution to breast cancer as BRCA1 and BRCA2," said Dr. Olopade. "You might hear about [the proteins] p-53, p-10, but there's still a lot of work to be done in terms of finding genetic contributions to breast cancer."
Currently, there are no proven means to prevent breast cancer. A woman's best chance of surviving breast cancer is to detect it early, through regular self and clinical breast exams, and mammography. However, for women at higher risk than normal of developing breast cancer, new drugs have been shown to reduce the risk of developing the disease.
Hormonal Treatments
Estrogen is a hormone that is necessary for sexual development and functioning of female organs important for childbearing, such as the ovaries and the uterus. Estrogen also helps maintain the health of the heart and bones. However, a woman's risk for breast cancer is associated with increased levels of estrogen.
"Many breast cancers are hormone-dependent, which means that estrogen stimulates their growth by 'switching on' estrogen receptors in the cancer cells. Without estrogen, the cancer cells do not grow and eventually die," explained Dr. Olopade.
During the years between puberty and menopause, the ovaries produce estrogen. After menopause, body fat becomes the primary source of estrogen.
"Recent studies continue to support the theory that breast cancer risk is associated with a lifetime exposure to estrogen," said Dr. Olopade. "For instance, women who began menstruating early and had a late menopause are at an increased risk for breast cancer because they were exposed to estrogen for a longer period of time. Another example is women who gain weight just before or after menopause: after menopause, when the ovaries no longer make estrogen, body fat is the primary source for estrogen made by the body. Women with a higher level of body fat during the post-menopausal years have a higher level of estrogen in the body than do thinner women," she added.
Anti-estrogen therapy uses drugs to block the effects of hormones—especially estrogen—that have the ability to promote the growth of breast cancer. The goal of anti-estrogen therapy is to deprive cancer cells of the estrogen that triggers their growth and multiplication.
A promising new class of anti-estrogen drugs that may prevent breast cancer is called "selective estrogen receptor modulators" (SERMS). Drugs that fall into this class include tamoxifen (Nolvadex) and raloxifene (Evista). "Though SERMS act like hormone estrogen in some ways, they also block its effect on the body," explained Dr. Olopade.
In the late 1990s, tamoxifen was shown to reduce the risk of breast cancer by 49% in women at high risk. However, because tamoxifen was also associated with serious side effects, such as blood clots and endometrial cancer, researchers are now comparing it to raloxifene in the ongoing national Study of Tamoxifen and Raloxifene (STAR) Trial to see if raloxifene can reduce the risk of breast cancer without causing such serious side effects.
Researchers are also examining a variety of different factors that may enhance or reduce a woman's exposure to estrogen, including factors such as diet, alcohol consumption, birth control pills, and physical activity.
Screening
There has been much debate surrounding breast cancer screening. However, it is generally agreed upon that women at an average risk of breast cancer should undergo the following screening tests:- A clinical breast exam—a breast exam performed by a doctor—at least every three years between the ages of 20 and 40, and every year starting at age 40.
- An X-ray of the breast, also called a mammogram, every year, starting at age 40.
For women with an increased risk of breast cancer, experts recommend mammograms beginning at age 30, or five years before the earliest onset of the disease in their family.
Women who have been shown to have mutations in the BRCA1 and BRCA2 genes may choose to undergo additional screening and prevention strategies, such as:- Screening earlier and more frequently than women at average risk for breast cancer.
- Undergoing preventive surgery to remove the ovaries and fallopian tubes. This surgery has been shown to reduce breast and ovarian cancer risk by 75% in women with mutations in the BRCA genes.
Screening Tests
There are many different ways to screen for breast cancer, including the following:- Conventional mammography is the standard screening test for breast cancer. Although it is not 100% accurate, it detects many early breast cancers. It can also be used to spot tiny deposits of calcium in the breast—called microcalcifications—that cannot be felt, but may indicate the presence of cancer.
- Digital mammography is a relatively new test that was approved for use by the U.S. Food and Drug Administration in 2000. Using this technology, breast images are displayed on a computer monitor and can be manipulated by a radiologist to magnify or zoom in on an area to examine differences between tissues. A large study is under way to compare the effectiveness of digital versus conventional mammography.
- Ultrasound is not routinely used for breast cancer screening, but can sometimes distinguish solid tumors from fluid-filled cysts. Ultrasound cannot detect microcalcifications.
- Contrast-enhanced magnetic resonance imaging (MRI) is not used for routine breast cancer screening, but clinical trials are evaluating it for screening certain women, such as young women at high risk for breast cancer. An MRI uses a magnetic field to produce the image of an internal organ on a computer. Breast MRI is used primarily to evaluate breast implants for leaks or ruptures, and to assess abnormal areas seen on a mammogram or felt after breast surgery or radiation therapy.
- Positron emission tomography (PET) scanning creates computerized images of chemical changes that take place in tissue. While not routinely used for breast cancer screening, PET scans may be used to determine whether a breast mass is cancerous, and to evaluate breast cancer that has recurred. A National Cancer Institute–sponsored clinical trial is evaluating PET scanning in women with breast cancer and comparing the results with findings from other imaging and diagnostic techniques. This trial is also studying the effectiveness of PET scanning to track a tumor's response to treatment.
- Ductal lavage is an experimental technique of collecting samples of cells from breast ducts for analysis. The cells are checked under a microscope to identify changes that may indicate cancer or changes that may increase the risk for breast cancer. The usefulness of ductal lavage is still under study.
Research on the Horizon
Aromatase inhibitors are another kind of anti-estrogen drug being studied to prevent breast cancers. Drugs that fall into this class of drugs include anastrozole (Arimidex) and letrozole (Femara).
Aromatase inhibitors work by lowering the body's production of estrogen. These types of drugs are only used in women who've gone through menopause because they lower the amount of estrogen that's produced outside the ovaries, such as in muscle and fat tissue.
Currently, aromatase inhibitors are only used in the treatment of breast cancer. "The question is: why wait until women develop breast cancer? Can we move these drugs into the prevention setting?" suggested Dr. Olopade. While these drugs have shown some promise in preventing breast cancer in clinical trials, they have also been associated with a significantly increased risk for the development of osteoporosis.
Several other studies are currently being conducted to test other therapies that may be effective in preventing breast cancer. "The list goes on and on in terms of drugs that are in the pipeline to test as prevention," said Dr. Olopade.
Lung Cancer
Each year, 172,000 people in the United States are diagnosed with lung cancer. In 2003, lung cancer will cause more than 157,000 deaths, making it the leading cause of cancer deaths in both men and women.
There are two major types of lung cancer: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). The term "small cell" refers to how the cancer cells appear under a microscope.
NSCLC is the most common kind of lung cancer and affects the epithelial cells. Epithelial cells line the airways and produce mucus, a substance that protects the lung. SCLC is believed to begin in the nerve cells or hormone-producing cells.
Risk and Prevention
"Lung cancer is the most preventable of all cancers because the vast majority of cases are caused by tobacco use," said Paul A. Bunn, Jr., MD, ASCO President and Director of the University of Colorado Cancer Center. Smoking is, by far, the leading risk factor for lung cancer.
"Over 90% of the people who become addicted to nicotine do so when they are a teenager, and it does appear you're more likely to become addicted when you are a teenager," said Dr. Bunn. He indicated that the good news is that the number of youth who smoke is less than in 1997, but the bad news is that it's still higher than it was a decade ago.
"The really bad news is that the percentage of youth who are smoking is higher than the percentage of adults who are smoking, and that means that in the future, these youth will become adult smokers," Dr. Bunn explained. "So if you think we're making tremendous leaps and bounds forward in the United States, think again."
Lung cancer death in men has been decreasing due to a corresponding decline in the use of tobacco products by men since the Surgeon General's report on smoking was released in 1964. Today, 25% of American men smoke.
At the time of the Surgeon General's report, only 19% of American women smoked, compared to approximately 23% today. In the 1980s, lung cancer overtook breast cancer as the number-one cause of cancer death in women, and while breast cancer deaths in women continue to decline, lung cancer deaths in women are only beginning to plateau. "Within five years, there will be twice as many lung cancer deaths as breast cancer deaths," said Dr. Bunn.
"We do know that the more you smoke, the greater your risk of lung cancer," said Dr. Bunn. "And if you're a heavy smoker—say two packs a day—your risk is more than 20 times that of someone who never smoked."
Nearly 87% of lung cancers are directly caused by smoking. Another three to five percent are believed to be caused by environmental, or second-hand, smoke. Second-hand smoke is the smoke a non-smoker inhales in the presence of someone who is smoking. "There's absolutely no question that second-hand smoke or passive smoking exposure causes a percentage of lung cancer cases," said Dr. Bunn.
Currently, tobacco-related deaths account for four million deaths worldwide. About a million and half of those are related to lung cancer, while the others are related to cardiovascular disease, stroke, or lung disease.
"By 2030, tobacco use will kill 10 million people worldwide, and that's far more than any other disease or problem, including AIDS, or SARS, and all the viruses put together," said Dr. Bunn.
Therefore, the most effective way to prevent lung cancer is to avoid smoking altogether. For people who smoke, the best way to reduce lung cancer risk is to quit. "Smokers who quit can reduce their risk of lung cancer immediately, but the level of risk declines slowly and will never reach those of a non-smoker," said Dr. Bunn.
Chemoprevention
Researchers are investigating the use of several chemopreventive therapies to determine if they might prevent lung cancer in former smokers. Chemoprevention is the use of specific natural or man-made substances to reverse or prevent cancer growth. "Chemoprevention is an area of active clinical research, but it is not a standard therapy," said Dr. Bunn.
There have been intensive studies of chemoprevention in lung cancer, but so far, none of these treatments have been shown to reduce lung cancer.
The following chemopreventive therapies are currently being investigated in clinical trials:- Budesonide, a steroid drug used to treat asthma, is currently in clinical trials to see if it can prevent precancerous lung tissue from becoming cancerous.
- Some research has shown that nonsteroidal anti-inflammatory agents (NSAIDs), such as the common household drug aspirin, may reduce lung cancer risk.
- Preliminary prevention trials show that certain drugs that block the actions of a protein called the epidermal growth factor receptor (EGFR) may prevent lung cancer. EGFR is necessary for the growth of many cancer cells, including lung cancer.
While cigarette smoking is the main cause of lung cancer, there are also other causes of lung cancer, and non-smokers can develop lung cancer as well. For example, asbestos is another risk factor for lung cancer. Asbestos is a generic name given to six minerals that have been used in a variety of products, including insulation, vehicle brakes, and cement. People who work with asbestos have a higher risk of getting lung cancer. If they also smoke, their risk is greatly increased. Fortunately, the government has practically eliminated the use of asbestos in the work-place and in home products altogether.
Exposure to radon—an invisible and odorless natural gas—has also been linked to lung cancer. Most hardware stores have kits that test home radon levels, and basements can be treated to reduce radon exposure.
Yet smoking remains the number-one cause of lung cancer. For this reason, many researchers believe that prevention offers the greatest opportunity to fight lung cancer, according to Dr. Bunn.
Studies are currently underway to look at how best to help people quit smoking through counseling, nicotine replacement, and medications. Other studies are exploring ways to convince young people never to begin smoking in the first place.
Screening
When lung cancer is diagnosed, it is often in an advanced stage. This means that the cancer has already metastasized, or spread beyond the lung, to another part of the body.
There are currently no effective screening tests for lung cancer. However, Dr. Bunn indicated a number of screening methods are being studied in clinical trials.- The National Lung Screening Trial (NLST) is comparing conventional chest X-rays with a technology called spiral (or helical) computed tomography (CT) to determine their effectiveness in detecting early lung cancers in long-time, heavy smokers. Spiral CT scan is a newer version of a conventional CT scan. A CT scan is a type of X-ray that uses a computer to produce a three-dimensional picture of the exact size and location of a tumor. Unlike the conventional CT, during the spiral CT the X-ray beam remains on continuously and rotates around the patient as the patient is moved through the image chamber.
Both chest X-rays and spiral CT scans have been used to find lung cancer early. So far, neither chest X-rays nor spiral CT scans has been shown to reduce a person's chance of dying from lung cancer. The NLST study, which will enroll up to 50,000 people over an eight-year period, will aim to show if either test is better at reducing deaths from this disease.
- The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, sponsored by the National Cancer Institute (NCI), is comparing conventional chest X-rays to no screening at all, with the hope of combining its results with those of the NLST. This would allow a complete comparison of spiral CT, conventional chest X-rays, and no screening.
- Methylated DNA is a genetic marker that may be a sign of early lung cancer. Studies are underway to see if detecting methylated DNA in the sputum (mucus coughed up from the lungs) or blood can be used to detect the disease early.
Research on the Horizon
Because lung cancer is most curable in its early stages, researchers are interested in screening patients for lung cancer before they show any symptoms of the disease. There are currently no tests effective in screening the general population for lung cancer. However, many advances in imaging techniques are currently being studied, with the hope that they might result in a more sensitive and specific method for detecting lung cancer early. In addition, molecules detected in the blood or sputum may suggest the presence of lung cancer before it is even detectable on a CT scan.
Cervical Cancer
Cervical cancer, or cancer of the cervix, used to be one of the most common causes of cancer death in American women. However, when found and treated early, cervical cancer often can be cured. Between 1955 and 1992, the number of deaths from cervical cancer in the U.S. declined by 74%.
"The main reason for this change is the use of the Pap test to find cervical cancer early," said Caroline D. Runowicz, MD, Vice Chairman of the Department of Obstetrics and Gynecology at St. Luke's-Roosevelt Hospital Center in New York.
Cervical cancer begins in the lining of the cervix. The cervix is the lower part of the uterus. There are two main types of cervical cancer: squamous cell carcinomas and adenocarcinomas. About 85% to 90% of cervical cancers are squamous cell carcinomas. The other 10% to 15% are adenocarcinomas. There are also a few other rare types of cancer of the cervix.
Cervical cancer does not form suddenly, but typically grows very slowly. "Over a period of several years, some cells on the surface of the cervix begin to change from normal to abnormal, and then to cancer," explained Dr. Runowicz.
Some of the abnormal changes may go away without treatment, but others are pre-cancerous and need treatment to stop them from becoming cancer. This pre-cancerous phase is called "dysplasia."
Risk and Prevention
Most cervical cancer can be prevented. The first way to prevent cervical cancer is by preventing pre-cancers. This is best done by avoiding infection of the cervix with the human papilloma virus (HPV), a virus that is spread through sexual contact.
Certain types of HPV cause genital warts. The types of HPV that cause raised external genital warts are not linked with cancer. Other types can cause abnormal skin changes on the genital skin, usually on a female's cervix.
"It is clear that HPV is the underlying cause of cervical cancer, but it's insufficient in and of itself; it has to have a co-factor," said Dr. Runowicz. "Co-factors include things like smoking, the birth control pill, and other infections, to name a few."
However, while most cervical cancer is caused by HPV, Dr. Runowicz noted that most cases of HPV will not lead to cancer.
She offered the following tips for lowering risk of HPV:- Limit the number of sexual partners. HPV is easily transmitted during sex, and the risk of infection increases if women have many sexual partners.
- Don't have sex with people who have genital warts. "However," Dr. Runowicz warns, "HPV does not always produce warts or other symptoms, so it's hard to tell if someone is infected."
- Quit smoking. "Smoking may raise the risk of cervical cancer in women exposed to HPV by slowing the body's efforts to get rid of HPV infection and damaging cervical cells," Dr. Runowicz explained.
Screening
The second way to prevent cervical cancer is through the early detection of abnormal cells with a Pap test, a screening test for cervical cancer. There are two types of Pap tests:- The regular Pap test, in which cells are scraped from a woman's cervix and smeared on a microscope slide for laboratory analysis.
- The liquid-based Pap test, in which the cells are scraped from a woman's cervix and placed in a special liquid before being transferred onto the slide.
Pap tests can detect abnormal cervical cells early when they are easiest to treat. In 2002, the American Cancer Society issued the following screening recommendations:- All women should begin having Pap smears when they become sexually active, or at age 21, whichever comes first. The test should be done every year if the regular Pap test is used, or every two to three years if the newer, liquid-based Pap test is used.
- "If you're older than the age of 30 years, and you've had three normal tests, then you can increase your interval to every two to three years," said Dr. Runowicz.
"If you're older than the age of 70, and you've had three normal tests, you can stop screening," said Dr. Runowicz.
Research on the Horizon
Because cervical cancer is highly treatable when detected early, researchers are developing better ways to detect cervical cancer. Though the Pap smear test is a useful screening tool for cervical cancer, it can also miss early evidence of cancer. Recently, researchers have found that combining it with a test to detect HPV lowers the error rate. In March 2003, an FDA panel recommended that Pap tests and HPV tests be used together when screening for cervical cancer in women over 29 years of age. The HPV test is already being used as a secondary test in women with abnormal Pap test results.
Several studies also show that nutrition is playing an increasing role in cervical cancer prevention. However, some research shows that supplementing a woman's diet with folic acid or beta-carotene may actually have a negative effect. "So it's really good to eat six fruits and vegetables everyday and not overuse supplements," advised Dr. Runowicz.
Promising research is also currently being conducted to evaluate a vaccine against HPV-16, a type of HPV that affects 20% of all adults and that has been linked to cervical cancer. A recent study in the New England Journal of Medicine showed that the vaccine reduced the occurrence of becoming infected with either HPV or cervical intraepithelial neoplasia (CIN), an infection of the cervix.
While Dr. Runowicz found these findings exciting, she also cautioned against the vaccine's widespread use in young women, saying there are a lot of questions that still need to be addressed.
Ovarian Cancer
Ovarian cancer is the fifth leading cause of death in women. However, when ovarian cancer is diagnosed before it has spread beyond the ovaries, a woman's chance of living five years beyond her diagnosis is more than 90%.
"Unfortunately, there are still 14,000 deaths each year from ovarian cancer, and it is the most lethal of the gynecological cancers," said Dr. Runowicz.
Ovarian cancer begins in a woman's ovaries. The ovaries are part of a woman's reproductive system. Every woman has two ovaries, located on either side of the uterus. The ovaries produce the eggs that are needed for reproduction, and are the primary source of the female sex hormones, estrogen and progesterone.
There are two types of ovarian tumors: benign and malignant. Benign ovarian tumors are not cancerous. They can be eliminated by removing the ovary or the part of the ovary where the tumor is located. However, the other type of ovarian tumors—malignant tumors—are cancerous.
There are three types of malignant ovarian tumors:- Epithelial carcinomas, which make up 85% to 90% of ovarian cancers, start in the cells on the outer surface of the ovary. Epithelial carcinomas are difficult to diagnose, and 70% of these types of ovarian cancers are not found until the disease has moved from the ovaries into another part of the body.
- Germ cell tumors develop on the inside part of the ovary, where the eggs are produced. Germ cell tumors are an uncommon form of ovarian cancer.
- Stromal tumors are a rare form of ovarian cancer that develop in the tissue cells that hold the ovaries together.
Early cancers of the ovary often have no symptoms, which is why ovarian cancer is often referred to as the silent killer. "Patients, when they present with symptoms, present with symptoms that are very vague and not necessarily pointing toward the ovary as the source of the symptoms," said Dr. Runowicz.
For this reason, and because the ovaries are deep within the body (making tumors difficult to detect), only 25% of all ovarian cancers are found at an early stage.
Risk and Prevention
While doctors do not yet know what causes ovarian cancer, they have identified certain factors involved in either increasing or decreasing ovarian cancer risk.
The following factors have been shown to reduce ovarian cancer risk:- Taking birth control pills for at least five years reduces ovarian cancer risk.
- Pregnancy and breastfeeding seem to lower the risk of ovarian cancer, especially when a woman has her first child before age 30.
- Women who have had a hysterectomy (the removal of the uterus and cervix) or a tubal ligation (having the fallopian tubes tied to prevent pregnancy) may have a lower risk of developing ovarian cancer.
- "Sometimes women with a very strong family history of ovarian cancer may choose to have surgery to remove both ovaries," said Dr. Runowicz. This type of surgery is called a prophylactic oophorectomy.
However, cautions Dr. Runowicz, "Removing the ovaries lowers the risk of ovarian cancer, but does not eliminate it entirely since cancer can still form in the cells lining the pelvic cavity where the ovaries were located."
Research has shown the following factors to increase the risk of ovarian cancer:- The most significant risk factor for developing ovarian cancer is age.
- A woman whose mother or sister has had ovarian cancer has a higher than average risk of developing ovarian cancer.
- Some research has linked hormone replacement therapy (HRT), also called hormone therapy, to an increased risk of ovarian cancer in postmenopausal women.
- Doctors now know that changes in certain genes can increase a woman's risk of ovarian cancer.
Researchers are continuing to develop better ways to detect these changes, so women who have these genetic differences may consider preventive surgery or other measures to reduce their risk.
"Most cases of ovarian cancer are not explained by any known risk factors," said Dr. Runowicz. "Take, for instance, a family history. This is one of the risk factors associated with ovarian cancer, and yet 90% to 95% of women diagnosed with ovarian cancer have no family history of the disease."
Research on the Horizon
Researchers and clinicians are constantly working to create better diagnostic procedures and treatments. Currently, there are no effective methods to screen for ovarian cancer in the general population.
However, there is ongoing research at a number of cancer centers specifically evaluating new genetic markers for the early detection of ovarian cancer. For example, a proteomic analysis, a blood test that pinpoints differences in protein patterns, is currently being studied in women with ovarian cancer and is showing promise for detecting early-stage disease. The test seeks patterns in the tens of thousands of proteins circulating in the bloodstream.
For women at high risk for ovarian cancer, transvaginal ultrasound is now being used to screen for the disease. Transvaginal ultrasound is a diagnostic technique that uses sound waves to detect abnormalities, including tumors. A computer creates a picture based on sound waves emitted from a transducer inserted into the vagina. The value of this technique in decreasing ovarian cancer death is currently being studied in women at high risk for ovarian cancer when used in conjunction with blood tests for CA125, a protein that may become elevated in women with ovarian cancer. However, because CA125 levels may also rise in response to other conditions, the test for the protein is not specific to ovarian cancer.
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