Zanmbeel

Friday, October 12, 2007

Colonoscopy

INTRODUCTION — Patients who require colonoscopy may have some questions and concerns about the procedure. This handout will provide information about colonoscopy and answers to questions that patients often ask.

Colonoscopy is a safe procedure that provides information other tests may not be able to give. A colonoscopy is an examination of the lower part of the gastrointestinal tract, which is called the colon or large intestine (bowel). It is performed by an endoscopist, a physician with special training in endoscopy procedures. The colonoscope is inserted into the anus and advanced through the entire colon (to the cecum) and possibly a short distance into the small intestine. The procedure generally between twenty minutes and one hour.

REASONS FOR COLONOSCOPY — The most common reasons for colonoscopy are to evaluate the following: As a screening exam for anyone over age 50 Blood in the stool or rectal bleeding Dark/black stools Persistent diarrhea Iron deficiency anemia (a decrease in blood count due to loss of iron) Significant, unexplained weight loss, accompanied by gastrointestinal symptoms A family history of colon cancer To follow up an abnormal barium enema A history of previous colon polyps or colon cancer Surveillance in people with ulcerative colitis For the medical management of chronic inflammatory bowel disease Chronic, unexplained abdominal pain.

PREPARATION — The endoscopy unit will provide specific instructions about how to prepare for the examination. The instructions are designed to maximize safety during and after the examination, minimize possible complications, and allow the endoscopist to fully view the colon.

It is important to read the instructions ahead of time and follow them carefully; patients who have questions should speak with their healthcare provider or the endoscopy unit.

The inside lining of the colon must be cleaned of stool to permit the endoscopist to complete a thorough examination. This is accomplished by restricting what is eaten and by using purgatives. What to eat — As a general rule, patients should not eat any solid food for at least one day before the examination. Only clear liquids (such as juices without pulp, bouillon, ginger ale) or clear gelatin (flavored is fine, but without added fruit) are recommended. The doctor's office or endoscopy unit will supply a list of fluids that are allowed. Purgatives — There are two methods commonly used to empty the bowel of stool. The first involves drinking a gallon of an undigestible solution (Go-Lytely®, and others) that causes temporary diarrhea. It comes in several flavors, which, unfortunately, only partially mask a somewhat unpleasant taste. Refrigerating the solution may make it more palatable. Drinking such a large volume of cold solution may cause a patient to feel chilled, but the sensation is temporary. Do not add flavoring to the solution. Many patients say that drinking the purgative solution is the most unpleasant part of the examination.

The second method involves drinking a solution called Fleets® Phosphosoda, along with several cups of liquid. This preparation is easier to consume than the purgative described above. However, the solution contains a large amount of phosphorus, which may be a problem for people with heart or kidney conditions. Medications — Some medications, such as aspirin and iron preparations, should be discontinued for one to two weeks before the examination. Aspirin and pain killers such as Motrin (which contains ibuprofen) slightly increase the risk of bleeding. Patients who take a blood thinning medication should consult with their doctor as to when they should stop taking it. Patients should also ask about medications for diabetes, heart or lung disease, high blood pressure, or seizure disorders. Some medications should not be stopped, and many of them can be taken the examination. Patients who take antibiotics before dental procedures should ask if they will be needed before colonoscopy. Transportation home — Patients need to arrange for someone to escort them safely home after the examination. Although patients will be awake by the time of discharge, the sedative medications cause changes in reflexes and judgment that cause a person to feel well but can interfere with the ability to make decisions, similar to the effect of alcohol.

WHAT TO EXPECT — Prior to the endoscopy, a nurse will ask questions to ensure the patient understands the procedure and the reason it is planned. The nurse will ask questions to ensure the patient has prepared properly for the procedure. A doctor will also review the procedure, including possible complications, and will ask patients to sign a consent form.

The nurse will start an intravenous line (insert a needle into a vein in the hand or arm) to administer medications. The intravenous line insertion feels like a pin prick, similar to having blood drawn. The vital signs (blood pressure, heart rate, and blood oxygen level) will be monitored before, during, and after the examination. The monitoring is not painful. Some patients will be given oxygen during the examination.

THE PROCEDURE — The colonoscopy will be performed while the patient lies on their left side. Medications will be administered through the intravenous line. Most endoscopy units use a combination of a sedative (to help patients relax), and a narcotic (to prevent discomfort). Many people sleep during the examination while others are very relaxed, comfortable, and generally not aware of the examination.

The colonoscope is a flexible tube, approximately the size of the index finger. It has a lens and a light source that allows the endoscopist to look into the scope or at a TV monitor. The image on the TV monitor is magnified many times so the endoscopist can see small changes in tissue.

The endoscope contains channels that allow the endoscopist to obtain biopsies (small pieces of tissue), remove polyps and to introduce or withdraw fluid or air. Polyps are extra growths of tissue that can range in size from the tip of a pen to several inches (doctors measure them in millimeters and centimeters). Most polyps are benign (not cancerous) but can turn into cancers if left to grow for a very long time. As a result, they are usually removed so they can be analyzed under the microscope. This does not hurt since the lining of the colon does not sense pain.

Air is introduced through the scope to open up the colon so that the scope can be moved forward and to allow the endoscopist to see. Patients may experience a feeling of bloating or gas cramps from the air as it distends the colon. Try not to be embarrassed about releasing the air through the rectum; patients should let their physician know if they are uncomfortable

RECOVERY — After the colonoscopy, a patient will be observed until the effects of the sedative medication are gone. The most common discomfort after colonoscopy is a feeling of bloating and gas cramps. Patients may also feel groggy from the sedation medications. Patients should not return to work that day. Most patients are able to eat a regular diet after the examination. Patients should ask about when it is safe to restart aspirin or blood thinning medications.

COMPLICATIONS — Colonoscopy is a safe procedure and complications are rare, but can occur: Bleeding can occur from biopsies or the removal of polyps, but it is usually minimal and stops quickly or can be controlled. The colonoscope can cause a tear or hole in the tissue being examined, which is a serious problem, but, fortunately, very uncommon. Adverse reactions to the medications used to sedate you are possible. The endoscopy team (doctors and nurses) will ask about previous medication allergies or reactions and about health problems such as heart, lung, kidney, or liver disease. The medications can also produce irritation in the vein at the site of the intravenous line. If redness, swelling, or warmth occur, warm to hot wet towels applied to the site may relieve the discomfort. If the discomfort persists, notify the endoscopy unit.

The following symptoms should be reported immediately: Severe abdominal pain (not just gas cramps) A firm, distended abdomen Vomiting Fever Bleeding greater than a few tablespoons.

AFTER COLONOSCOPY — Although patients worry about discomforts of the examination, most people tolerate it very well and feel fine afterwards. Some fatigue after the examination is common. Patients should plan to take it easy and relax the rest of the day.

The endoscopist can describe the result of their examination before the patient leaves the endoscopy unit. If biopsies have been taken or polyps removed, the patient should call for results within one to two weeks.

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine

(www.nlm.nih.gov/medlineplus/healthtopics.html)
The American Society of Gastrointestinal Endoscopy

(www.askasge.org)

[1-3]

Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Rex, DK, Johnson, DA, Lieberman, DA, et al. Colorectal cancer prevention 2000: screening recommendations of the American College of Gastroenterology. American College of Gastroenterology. Am J Gastroenterol 2000; 95:868.
2. Lieberman, DA, Weiss, DG, Bond, JH, et al. Use of colonoscopy to screen asymptomatic adults for colorectal cancer. Veterans Affairs Cooperative Study Group 380. N Engl J Med 2000; 343:162.
3. Singh, H, Turner, D, Xue, L, et al. Risk of developing colorectal cancer following a negative colonoscopy examination: evidence for a 10-year interval between colonoscopies. JAMA 2006; 295:2366.

Colonoscopy

Colon polyps

THE SIGNIFICANCE OF POLYPS — The presence of polyps in the colon or rectum often raises questions for patients and their family. What is the significance of finding a polyp? Does this mean that I have, or will develop, colon or rectal (colorectal) cancer? Will a polyp require surgery?

Some types of polyps (called adenomas) have the potential to become cancerous while others (hyperplastic or inflammatory polyps) have virtually no chance of becoming cancerous.

When discussing colon polyps, the following points should be considered: Polyps are common (they occur in 30-50 percent of adults) Not all polyps will become cancer It takes many years for a polyp become cancerous Polyps can be completely and safely removed

The best course of action when a polyp is found depends upon the type, size, and location of the polyps and the way in which they were removed. Most people who have an adenoma removed will require a follow up examination; this allows the clinician to be sure that all adenomas have been removed.

CAUSES — Polyps are very common in men and women of all races who live in industrialized countries, which suggests that dietary and environmental factors are important in their development.

Lifestyle — Although the exact causes are not completely understood, lifestyle risk factors include the following: A high fat diet A diet high in red meat A low fiber diet Cigarette smoking Obesity

On the other hand, use of aspirin and other NSAIDs and calcium intake may protect against the development of colon cancer. (See "Patient information: Screening for colon cancer").

Aging — Colorectal cancer is uncommon before age 40. Ninety percent of cases occur after age 50, with men and women being equally affected; therefore, colon cancer screening usually begins at age 50 for both sexes. It takes approximately 10 years for a small polyp to grow and develop into cancer.

Family history and genetics — Polyps and colon cancer tend to run in families, which suggests that genetic factors are also important in their development. Research on the genetic basis of colon cancer is ongoing.

Any history of colon polyps or colon cancer in the family should be discussed with a healthcare provider, particularly if cancer developed at an early age, in close relatives, or in multiple family members. As a general rule, screening for colon cancer begins at an earlier age in people with a family history of cancer or polyps.

Rare genetic diseases can cause high rates of colorectal cancer relatively early in adult life. One disease that causes multiple colon polyps is familial adenomatous polyposis (FAP). Hereditary Non-Polyposis Colon Cancer (HNPCC) also significantly increases the risk of colon cancer, often beginning in the 20s and 30s, but does not cause a large number of polyps. Testing for these genes may be recommended for families with high rates of colorectal cancer, but is not generally recommended for other groups.

TYPES OF POLYPS — The two most common types of polyps are hyperplastic and adenomatous polyps. Other types of polyps can also be found in the colon, although these are far less common and are not discussed here.

Hyperplastic polyps — Hyperplastic polyps are usually small, located in the end-portion of the colon (the rectum and sigmoid colon), have no potential to become malignant, and are not concerning (show figure 1). It is not always possible to distinguish a hyperplastic polyp from an adenomatous polyp based upon appearance, which means that hyperplastic polyps are often removed or biopsied to allow microscopic examination.

Adenomatous polyps — Two-thirds of colon polyps are adenomas. Most of these polyps do not develop into cancer, although they have the potential to become cancerous. Adenomas are classified by their size, general appearance, and their specific features as seen under the microscope.

As a general rule, the larger the adenoma, the more likely it is to eventually become a cancer; large adenomas may already contain cancer cells. As a result, large polyps are usually biopsied (a small sample of tissue is removed) or removed completely to allow for microscopic examination.

DIAGNOSIS — Polyps usually do not cause symptoms. They are most commonly detected during a colon cancer screening examinations (such as flexible sigmoidoscopy or colonoscopy, show endoscopy 1) or during testing after a positive stool blood test. Polyps can also be detected on a barium enema x-ray, although small polyps are less often seen on x-ray and cannot be removed during the examination.

Colonoscopy is the best way to evaluate the colon because it allows the physician to see the entire lining of the colon and remove any polyps that are found. During colonoscopy, a physician inserts a very thin flexible tube with a light source and small camera into the anus. The tube is advanced through the entire length of the large intestine (colon). (See "Patient information: Colonoscopy").

The inside of the colon is a tube-like structure with a flat surface with curved folds. A polyp appears as a lump that protrudes into the inside of the colon (show endoscopy 1). The tissue covering a polyp may look the same as normal colon tissue, or, there may be tissue changes ranging from subtle color changes to ulceration and bleeding. Some polyps are flat ("sessile") and others extend out on a stalk ("pedunculated").

Colonoscopy is also the best test for the follow-up examination of polyps. New technologies are being developed that show promise for detecting polyps (including molecular genetic tests and "virtual colonoscopy" using CT or MRI technology). Further study is needed before these tests are recommended to the general public.

POLYP REMOVAL — Colorectal cancer is the second leading cause of cancer deaths in the United States, accounting for 14 percent of cancer deaths. Colorectal cancer is preventable if precancerous polyps (ie, adenomas) are detected and removed before they become malignant (cancerous). Over time, small polyps can change their structure and become cancerous. Polyps are removed when they are found on colonoscopy, which eliminates the potential for them to become malignant.

Procedure — The medical term for removing polyps is polypectomy. Most polypectomies can be performed through a colonoscope. Small polyps can be removed with an instrument that is inserted through the colonoscope and snips off small pieces of tissue (show endoscopy 2). Larger polyps are usually removed by placing a noose, or snare, around the polyp base and burning through it with electric cautery (show endoscopy 3). The cautery also helps to stop bleeding after the polyp is removed.

Polyp removal is not painful because the colon does not have the ability to feel pain. In addition, a sedative medication is given before the colonoscopy to prevent pain and induce sleep. Rarely, a polyp will be too large to remove during colonoscopy, which means that a surgical procedure will be needed at a later time.

Complications — Polypectomy is very safe, but it has a few risks and potential complications. The most common complications of polypectomy include bleeding and perforation (creating a hole in the colon). Fortunately, this occurs infrequently (one in a thousand patients having colonoscopy). Bleeding can usually be controlled during colonoscopy by cauterizing (applying heat) to the bleeding site; surgery is sometimes required for perforation.

After polyp removal — Medications that can increase bleeding, including aspirin, ibuprofen (Advil®, Motrin®), and naproxen (Aleve®), should be avoided for two weeks after polypectomy. Acetaminophen (Tylenol®) is safe to take. People who require anticoagulant medications such as warfarin (Coumadin®) should discuss how and when to resume this medication after polypectomy with their clinician.

A follow up appointment or phone call is usually scheduled after the polyp removal to discuss the results of the tissue analysis and the need for a repeat examination.

PREVENTION

Follow up examination — People with adenomatous polyps have an increased risk of developing more polyps, which are likely to be adenomatous. There is a 25 to 30 percent chance that adenomas will be present on a repeat colonoscopy done three years after initial polypectomy. Some of these polyps may have been present during the original examination, but were too small to detect. Other new polyps may also have developed.

After polyps are removed, repeat colonoscopy is recommended, usually three to five years after the initial colonoscopy. However, this time interval depends upon several factors: Characteristics of the polyps when they are analyzed under the microscope Number and size of the polyps The appearance of the colon during the colonoscopy. A bowel preparation is needed before colonoscopy to remove all traces of feces (stool). If the bowel prep was not completed, feces may remain in the colon, making it more difficult to see small to moderate size polyps. In this situation, follow up colonoscopy may be recommended sooner than three to five years later.

Persons who undergo screening (and re-screening) for colon cancer are much less likely to die from colon cancer. Thus, following screening guidelines is one of the most important measures.

Preventing colon cancer — Intensive research is underway to develop ways to prevent polyps and colon cancer with diet or with medications. A number of nutrients and medications have been identified that may reduce the risk of colon cancer. Guidelines issued by one of the major medical societies in the United States (the American College of Gastroenterology) suggest the following to prevent polyps from recurring: Eat a diet that is low in fat and high in fruits, vegetables, and fiber Maintain a normal body weight Avoid smoking and excessive alcohol use Consider taking a dietary supplementation with 3 g of calcium carbonate

(See "Patient information: Diet and health" and see "Patient information: Smoking cessation").

IMPLICATIONS FOR THE FAMILY — First-degree relatives (a parent, brother, sister, or child) of a person who has been diagnosed with an adenomatous polyp (or colorectal cancer) before the age of 60 years are at increased risk for adenomatous polyps and colorectal cancer compared to the general population. Thus, family members should be made aware if adenoma or colon cancer are diagnosed. While screening for polyps and cancer is recommended for all people at risk (typically beginning at age 50), those at increased risk should begin screening earlier, typically at age 40.

Relatives can be told the following: People who have one first-degree relative (parent, brother, sister, or child) with colorectal cancer or adenomatous polyps at a young age (before the age of 60 years), or two first-degree relatives diagnosed at any age, should begin screening earlier, typically at age 40, or 10 years younger than the earliest diagnosis in their family, whichever comes first. Screening should be repeated every five years. People who have one first-degree relative (parent, brother, sister, or child) with colorectal cancer or adenomatous polyps at age 60 or later should begin screening at age 40, and screening should be repeated similar to a person with an average risk of colon cancer. (See "Patient information: Screening for colon cancer" section on "Average risk"). People with a second-degree relative (grandparent, aunt, or uncle) or third-degree relative (great-grandparent or cousin) with colorectal cancer may be screened similar to a person with an average risk. (See "Patient information: Screening for colon cancer" section on "Average risk").

Some conditions, such as hereditary nonpolyposis colorectal cancer, familial adenomatous polyposis, and inflammatory bowel disease (eg, ulcerative colitis, Crohn's disease) significant increase the risk of colonic polyps or cancer in family members. Colon cancer screening in this group is discussed separately. (See "Patient information: Screening for colon cancer" section on "Increased risk").

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine

(www.nlm.nih.gov/medlineplus)
The American Gastroenterological Association

(www.gastro.org)
The American College of Gastroenterology

(www.acg.gi.org)
The American Society of Colon and Rectal Surgeon

(www.fascrs.org)

[1-3]

Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Winawer, S, Fletcher, R, Rex, D, et al. Colorectal cancer screening. Gastroenterology 2003; 124:544.
2. Winawer, SJ, Zauber, AG, Ho, MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy. N Engl J Med 1993; 329:1977.
3. Bond, JH. Polyp guideline: Diagnosis, treatment, and surveillance for patients with colorectal polyps. Am J Gastroenterol 2000; 95:3053.

Colon polyps

Tamoxifen and raloxifene for the prevention of breast cancer

INTRODUCTION — Approximately 210,000 women in the United States are newly diagnosed with breast cancer each year. Certain risk factors may increase the likelihood that a woman will develop breast cancer, including advancing age and a strong family history of breast cancer, among others. Based upon a careful risk assessment, healthcare providers sometimes recommend therapy with one of two medications (tamoxifen or raloxifene) to reduce the chance of developing breast cancer for women at increased risk. The term chemoprevention is applied to the use of a medication to prevent cancer from developing in a high-risk individual. (See "Patient information: Risk factors for breast cancer").

The following is a discussion of studies evaluating the effectiveness of both tamoxifen and raloxifene for breast cancer chemoprevention, possible adverse effects, and information about which women should consider taking one of these agents.

HOW DO TAMOXIFEN AND RALOXIFENE WORK? — Both tamoxifen and raloxifene are members of a drug class called Selective Estrogen Receptor Modulators (SERMs). The use of SERMs to prevent breast cancer in high-risk women came about because of the success of tamoxifen in reducing the occurrence of new cancers in the opposite breast of women who had early breast cancer. This finding suggested that tamoxifen might play a role in the prevention of breast cancer in women who have not yet developed breast cancer.

Drugs like SERMs work as breast cancer chemopreventive agents because they are able to interfere with the effect of the female hormone estrogen on certain tissues, such as the breast. Besides influencing the growth of breast tissue, estrogen performs a variety of other functions in a woman's body, including sexual development, proper functioning of the reproductive system, and maintaining bone strength.

Many cells in the body, especially within estrogen-sensitive tissues like the breast, contain specialized proteins that bind estrogen. These proteins are known as estrogen receptors (ERs). Both normal cells and cancerous cells within breast tissue may contain ERs; the binding of estrogen to these ERs stimulates the cells to grow and divide.

SERMs such as tamoxifen and raloxifene do not just prevent estrogen from interacting with its receptor. SERMS actually interact with ERs in different ways in different tissues of the body. Depending on the specific tissue, the effect can either be to block the effects of estrogen (called antiestrogenic effects, such as occurs in the breast tissue), or to mimic the effects of estrogen (called estrogenic effects). Thus, in the same person, a SERM such as tamoxifen can be antiestrogenic in some tissues and estrogenic in others (show figure 1). These effects can be both beneficial and detrimental: Both tamoxifen and raloxifene have antiestrogenic actions on both normal and cancerous breast tissue. This is beneficial because taking tamoxifen decreases cancer growth in women with breast cancer. In women at high risk of breast cancer, both tamoxifen and raloxifene can prevent new ER positive breast cancers. Tamoxifen and raloxifene also have antiestrogenic activity on certain parts of the brain. This can lead to many of the menopausal symptoms (eg, hot flashes, sweating, insomnia) that occur in 30 to 40 percent of women who take them. Tamoxifen and raloxifene are estrogenic in the bones of postmenopausal women. They can prevent loss of bone mass and decrease the risk of developing bone fractures of the spine. (See "Patient information: Osteoporosis causes, diagnosis, and screening" and see "Patient information: Osteoporosis prevention and treatment").

However, in premenopausal women, tamoxifen has an antiestrogenic effect on bones and can cause slight bone loss, which is generally reversible when the drug is stopped (if the woman is still menstruating). Tamoxifen and raloxifene are estrogenic in the liver, and they increase the liver's production of blood-clotting proteins. This results in a slight increase in the risk of stroke, particularly in women who are at high risk for these events (ie, cigarette smokers, those with a past history of blood clots). Higher levels of clotting proteins also increase the risk of blood clots in the major veins of the leg (deep vein thrombosis) and migration of such a blood clot to the lungs (pulmonary embolus). The risk may be slightly lower with raloxifene compared with tamoxifen. (See "Patient information: Venous thrombosis"). Tamoxifen is estrogenic in the endometrium (the lining of the uterus). Although most of the conditions that result from the growth of endometrial tissue are benign (eg, thickening of the lining of the uterus, or polyps), the risk of cancer of the uterus is increased by two- to threefold in women taking tamoxifen. Tamoxifen therapy may cause other bothersome side effects, including vaginal discharge and uterine bleeding.

In contrast, raloxifene is antiestrogenic in the endometrium, and does not appear to increase the risk of uterine cancer.

EFFECTIVENESS

Tamoxifen — One American and three European research studies have examined the effectiveness of tamoxifen for the prevention of breast cancer. Overall, the evidence from these studies suggests that tamoxifen can prevent hormonally responsive (ie, ER-positive) breast cancers from developing in women at risk for the disease.

The largest trial examining the benefit of tamoxifen, known as the NSABP P-1 study, included over 13,000 American women age 35 years and older who were at increased risk for breast cancer because of their age, family history, or personal history of breast disease.

The women who participated were randomly assigned to tamoxifen at a dose of 20 milligrams (mg) per day or an inactive substance (placebo). The study was stopped early when researchers determined that there was a 50 percent decrease in the risk of developing breast cancer in women who took tamoxifen [1].

Despite the evidence that it reduces the risk of developing breast cancer in high-risk women, tamoxifen has not been widely accepted for chemoprevention largely because of the lack of evidence that survival is improved in women who receive tamoxifen as a chemopreventive agent, and a small risk of serious adverse events, including uterine cancer and blood clots in the legs or lungs.

Raloxifene — Raloxifene is currently used for the prevention and treatment of osteoporosis in postmenopausal women. Several studies suggest that in postmenopausal women at high risk of developing breast cancer, raloxifene can reduce the risk of developing an invasive hormonally-responsive (ER positive) breast cancer.

Raloxifene was directly compared to tamoxifen in a large trial involving postmenopausal women at high risk of breast cancer (called the Study of Tamoxifen and Raloxifene, or STAR trial). Participants were postmenopausal women over the age of 35 with a risk of breast cancer of at least 1.66, as determined by the Gail model, or a prior history of a precancerous breast condition, lobular carcinoma in situ (LCIS). Both tamoxifen and raloxifene were equally effective at preventing invasive breast cancer but raloxifene had less effect on the uterus and lower risk of blood clots than tamoxifen [2]. However, raloxifene has only been tested in postmenopausal women; its benefit in premenopausal women is unknown.

PRECAUTIONS — Tamoxifen and raloxifene are not recommended for some women, including those who: Have a history of deep vein thrombosis or pulmonary embolism Require anticoagulant or blood thinning medications Smoke Are pregnant, planning on becoming pregnant, or breastfeeding (tamoxifen may cause birth defects if taken during pregnancy)

Women who use tamoxifen prior to menopause should use a non-hormonal method of birth control (such as condoms and a diaphragm), since oral contraceptives or other hormonal methods may alter the effectiveness of tamoxifen. A woman should immediately notify her doctor if she becomes pregnant while on tamoxifen. (See "Patient information: Contraception").

Women who use tamoxifen or raloxifene should be closely monitored by their healthcare provider. In particular, women should: Have an annual gynecologic examination, including a breast examination and, if recommended, a yearly mammogram and Pap smear (screening of the cervix for cancerous or precancerous cells). Any woman who finds a new breast lump should speak with her health care provider about the need for diagnostic testing (mammogram, ultrasound, biopsy). Immediately report any abnormal gynecologic symptoms, such as menstrual irregularities, abnormal vaginal bleeding or spotting, staining, or pelvic pressure or pain. (See "Patient information: Abnormal uterine bleeding"). Immediate medical care is needed if signs or symptoms of a blood clot develop, such as calf tenderness, swelling, pain, or severe, unexplained breathlessness.

AROMATASE INHIBITORS — Aromatase inhibitors such as anastrozole (Arimidex®), letrozole (Femara®), and exemestane (Aromasin®) are often used to treat women with hormone responsive breast cancer. Although data are not yet available, these agents are currently being studied in several trials for prevention of breast cancer.

SUMMARY

Who should consider chemoprevention? — We suggest chemoprevention with a SERM in premenopausal and postmenopausal women who meet the definition of high risk for breast cancer. At present, this includes women with a history of a precancerous breast condition called lobular carcinoma in situ (LCIS) and those who have a calculated five-year risk of developing breast cancer of 1.66 percent or higher, according to a system called the Gail model. The Gail model uses a woman's current age; age at menarche; age at first live birth; the number of first degree relatives with a history of breast cancer; and the number and pathologic findings of any breast biopsies to estimate the probability of breast cancer over time.

A computer program to calculate an individual woman's risk is available at 1-800-4CANCER, or online at www.cancer.gov/bcrisktool/Default.aspx [3]. This risk assessment tool was developed for health professionals; patients who use it on their own should speak with their clinician for help interpreting the results. In addition, the presence of breast cancer risk factors does not mean that cancer is inevitable. Many women with risk factors never develop breast cancer.

An important issue is that these models do not consider the risk of cancer associated with inherited breast cancer-predisposing genes such as BRCA1 and BRCA2. Preliminary data suggest that there is benefit of tamoxifen for women with these mutations, at least in the reduction of breast cancer in the opposite breast of women with a history of breast cancer. (See "Patient information: Genetic testing for breast and ovarian cancer").

In general, the following women are candidates for tamoxifen or raloxifene: All women who are older than 60 years Postmenopausal women who are between 35 and 59 and who have an increased risk of breast cancer of at least 1.66 (as determined by the Gail model) Postmenopausal women who are 35 or older and have a history of LCIS

Premenopausal women at high risk of developing breast cancer who wish to use a medication to reduce their risk should consider tamoxifen because there are no data about the safety of raloxifene in premenopausal women.

The optimal duration of tamoxifen or raloxifene therapy for the primary prevention of breast cancer is not known. Based upon studies in women with breast cancer, the current recommendation is five years.

Tamoxifen or raloxifene?

Compared to tamoxifen, raloxifene is associated with a significantly lower risk of cataracts and blood clots in the legs and lungs but more muscle and bone pain, pain with sexual intercourse, and weight gain.

Raloxifene probably does not increase the risk of uterine cancers. In addition, other gynecologic problems such as uterine bleeding and need for a hysterectomy, hot flashes, and urinary incontinence problems are less common with raloxifene.

Raloxifene is currently approved for the prevention and treatment of osteoporosis, but not yet for breast cancer prevention. However, raloxifene is being used more frequently for chemoprevention in postmenopausal women due to the lower risk of some of the most severe side effects associated with tamoxifen. At present, raloxifene is not used for breast cancer chemoprevention in premenopausal women because of the lack of data regarding safety in this population.

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. People Living With Cancer: The official patient information

Web site of the American Society of Clinical Oncology
(www.plwc.org/portal/site/PLWC)
National Comprehensive Cancer Network

(www.nccn.org/patients/patient_gls.asp)
National Cancer Institute

1-800-4-CANCER
(www.nci.nih.gov)
American Cancer Society

1-800-ACS-2345
(www.cancer.org)
Susan G. Komen Breast Cancer Foundation

(www.komen.org)

[1-17]

Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Fisher, B, Costantino, JP, Wickerham, DL, et al. Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and bowel Project P-1 Study. J Natl Cancer Inst 1998; 90:1371.
2. Vogel, VG, Constantino, JP, Wickerham, DL, et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes. JAMA 2006; 295:2727.
3. Breast cancer risk asssessment tool available online at at www.cancer.gov/bcrisktool/Default.aspx. (Accessed April 27, 2006).
4. Chlebowski, RT, Col, N, Winer, EP, et al. American Society of Clinical Oncology technology assessment of pharmacologic interventions for breast cancer risk reduction including tamoxifen, raloxifene, and aromatase inhibition. J Clin Oncol 2002; 20:3328.
5. Chemoprevention of breast cancer: recommendations and rationale. Ann Intern Med 2002; 137:56.
6. Gail, MH, Costantino, JP, Bryant, J, et al. Weighing the risks and benefits of tamoxifen treatment for preventing breast cancer. J Natl Cancer Inst 1999; 91:1829.
7. Cuzick, J. First results from the International Breast Cancer Intervention Study (IBIS-I): a randomised prevention trial. Lancet 2002; 360:817.
8. Veronesi, U, Maisonneuve, P, Rotmensz, N, et al. Italian randomized trial among women with hysterectomy: tamoxifen and hormone-dependent breast cancer in high-risk women. J Natl Cancer Inst 2003; 95:160.
9. Powles, T, Eeles, R, Ashley, S, et al. Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial. Lancet 1998; 352:98.
10. Cuzick, J, Powles, T, Veronesi, U, et al. Overview of the main outcomes in breast-cancer prevention trials. Lancet 2003; 361:296.
11. Cummings, SR, Eckert, S, Krueger, KA, et al. The effect of raloxifene on risk of breast cancer in postmenopausal women. Results from the MORE randomized trial. JAMA 1999; 281:2189.
12. Fisher, B, Costantino, JP, Wickerham, DL, et al. Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 2005; 97:1652.
13. King, MC, Wieand, S, Hale, K, et al. Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2. JAMA 2001; 286:2251.
14. Reis, SE, Costantino, JP, Wickerham, DL, et al. Cardiovascular effects of tamoxifen in women with and without heart disease: Breast Cancer Prevention Trial. J Natl Cancer Inst 2001; 93:16.
15. Wysowski, DK, Honig, SF, Beitz, J. Uterine sarcoma associated with tamoxifen use. N Engl J Med 2002; 346:1832.
16. Bergman, L, Beelen, ML, Gallee, MP, et al. Risk and prognosis of endometrial cancer after tamoxifen for breast cancer. Comprehensive Cancer Centres' ALERT Group. Assessment of Liver and Endometrial cancer Risk following Tamoxifen. Lancet 2000; 356:881.
17. ACOG committee opinion. Tamoxifen and endometrial cancer-Number 169, February 1996. Int J Gynaecol Obstet 1996; 53:197.

Tamoxifen and raloxifene for the prevention of breast cancer

Screening for breast cancer

INTRODUCTION — Cancer screening refers to the use of tests to detect cancer at an early stage, before it causes symptoms and hopefully at a time when it is curable. More than 200,000 women in the United States are newly diagnosed with breast cancer each year. About 40,000 women die each year of breast cancer, making it second only to lung cancer in cancer deaths among women.

The death rate from breast cancer has declined about 20 percent over the past decade [1]. This is due, in part, to the ability of increased screening to find the disease at earlier stages when the chances of successful recovery are higher. In fact, there is more scientific evidence supporting the use of screening tests for breast cancer than for any other type of cancer.

The information presented here is for women at usual risk of breast cancer. Women with a known genetic mutation, like BRCA1 and BRCA2, or who have several close relatives with breast cancer should see "Patient information: Genetic testing for breast and ovarian cancer" for information about screening recommendations.

SCREENING METHODS — There are three main methods of screening for breast cancer: mammography, clinical breast examination, and breast self-examination.

Mammography — A mammogram is a breast x-ray that is the best screening test for reducing the risk of dying from breast cancer. Early concerns about the radiation exposure from mammograms have lessened with the use of modern mammography equipment that exposes the breast to extremely low levels of radiation. The current level of radiation exposure is unlikely to significantly increase the risk of developing breast cancer.

The cost of mammograms is covered by most private insurances, Medicare, and Medicaid. The American Cancer Society has information about low cost mammograms that are available in most communities (1-800-ACS-2345).

Technique — Before the mammogram, patients are asked to undress from the waist up and wear a hospital gown. Each breast is x-rayed individually. The breast is flattened between two panels, which allows the radiologist to more easily see abnormalities. This can be uncomfortable, though the discomfort lasts for only a few seconds. Mammograms are most uncomfortable when done just before or at the beginning of the menstrual period; women should try to avoid scheduling their mammogram at these times, if possible.

Findings — The mammogram is interpreted by a radiologist. Sometimes the radiologist is present at the time of the mammogram; in these cases, a patient may be asked to wait a few minutes while the radiologist determines if anything requires further evaluation. So, a woman may be asked to have additional x-rays. All mammography facilities are required to send results within 30 days; patients must be contacted within five days if the mammogram is abnormal.

Breast cancer cannot be diagnosed by mammography alone. Women usually require further testing (eg, ultrasound or biopsy) if the mammogram shows a mass, new calcium deposits, or other abnormal findings. These findings do not always mean that a cancer has been found. One study found that 11 percent of mammograms performed in the United States require additional evaluation; the area in question was not cancer in more than 90 percent of these cases [2].

The abnormalities that radiologists typically look for on mammograms are calcifications and masses (show figure 1 and show figure 2). Macrocalcifications are large calcium deposits that most often represent degenerative changes in the breast such as might occur with aging or with previous trauma or inflammation. Macrocalcifications are common, particularly in women over the age of 50, and generally do not require a biopsy. Microcalcifications are small specks of calcium that sometimes suggest the presence of breast cancer. Depending upon the shape and pattern of microcalcifications, the radiologist may recommend a biopsy of the affected area or a repeat mammogram in three to six months. Masses that appear on mammograms may represent cancer or a variety of benign disorders such as cysts or fibroadenomas. Ultrasound or needle aspiration is often recommended to determine if a mass is a cyst. If it is not a cyst, biopsy may be necessary.

Clinical breast examination — Clinical breast examination is the visual and manual examination of the breasts by a health care provider. Both clinical breast examination and mammography appear to be important; studies show that about 50 percent of breast cancers found on screening were detected by both examination and mammography. Five to 10 percent are detected with examination and missed by mammography, and about 40 percent are detected by mammography and missed by examination.

Clinical breast examination is typically performed at the yearly physical examination. Healthcare providers usually inspect the breasts for any changes in size or shape and then palpate (feel) the breasts and the area under both arms for any change in texture or the presence of lumps.

Breast self-examination — Breast self-examination is a means of detecting changes in your breasts. It typically is performed at the same time each month. For women who are menstruating, this may be about one week after the menstrual period ends, when the breasts are least lumpy. In postmenopausal women who are not menstruating, this may be on the same day each month.

Most studies have not found breast self-examination to be beneficial. One large randomized trial found breast self-examination did not reduce the risk of dying from breast cancer but did result in women undergoing more breast biopsies for benign lumps [3]. Nevertheless, some women feel that practicing breast self-examination regularly improves their ability to detect subtle changes that would otherwise not have been appreciated. Breast self-examination is not a substitute for mammography or clinical breast examination by a health care professional.

The studies that have been performed to date suggest that performing breast self-examination correctly is important. Patients who want to perform self-examinations should ask their health care provider to demonstrate how to do it and how to tell the difference between normal tissue and suspicious lumps.

Breast MRI — Magnetic resonance imaging (MRI) uses a strong magnet rather than x-rays or radiation to create a detailed image of a part of the body. Breast MRI may be recommended to aid in the diagnosis of breast cancer in selected situations (show radiograph 1) [4]. MRI is not recommended to detect breast cancer in women who do not have a high risk of breast cancer because of the increased risk of a falsely positive result (when the MRI shows a suspicious mass that is not cancer). In addition, MRI is not as good as mammogram in detecting certain breast conditions, such as ductal carcinoma in situ.

RECOMMENDATIONS — All major North American groups that make recommendations about breast cancer screening recommend routine screening with both mammography and clinical breast examination for women ages 50 years and older. There is controversy about routine screening among women in their 40s, although over time, more and more groups are recommending screening for women in their 40s as well. The American Cancer Society, American College of Radiology, American Medical Association, United States Preventive Services Task Force, and American College of Obstetrics and Gynecology all recommend starting routine screening at age 40 years. The US Preventive Services Task Force and American Academy of Family Physicians recommends screening mammography every one to two years for women ages 40 and older [5]. The American College of Physicians and The Canadian Task Force on the Periodic Health Examination recommend beginning routine screening at age 50 years. A 1997 National Institutes of Health Consensus Development Conference Panel Report on breast cancer screening in women ages 40 to 49 years recommended that women in this age group decide individually about breast cancer screening with their health care provider [6]. A 2007 guideline from the American College of Physicians makes a similar recommendation [7].

Defining routine screening — Most North American expert groups suggest that women over age 50 be screened every year. Groups that recommend screening for women in their 40s have tended to shift from recommending every one to two years to recommending every year because of the evidence of more rapid tumor growth in younger women.

There are no clear data on the effectiveness of routine screening mammography in women over age 70 years. Some researchers believe that mammography is less useful in these women because they have a reduced life expectancy and tumor growth is usually slower in older women. However, most expert groups recommend that because the risk for breast cancer increases as women age, routine screening should be continued as long as a woman has a life expectancy of at least 10 years. The recommended interval for women over the age of 70 is one to two years, depending upon a woman's individual risk of breast cancer. (See "Patient information: Risk factors for breast cancer").

The bottom line — All women should discuss mammograms with their clinician starting at age 40. Mammograms have the highest rate of detecting breast cancer. Virtually every well-performed study to date has found that screening mammography in women ages 50 and older reduces the risk of dying from breast cancer. A summary of trials found a 22 percent reduction in mortality in women in this age group who had regular mammography compared with women who did not [8]. For women in their 40s, the protection is somewhat less, both because breast cancer is less common and because it is harder to find with screening (examination and imaging tests) in younger women.

There are trade-offs between the benefits and risks of mammography in detecting: Breast cancers (that may end a woman's life prematurely) Precancerous lesions such as ductal carcinoma in situ (DCIS) (that often do not progress) False-positive results (that cause anxiety and potentially require unnecessary testing)

All women, especially those in their 40s, should discuss their situation with a health care provider and decide together when to start screening. Some useful information when considering mammography screening is presented in the figures (show figure 3A-3B). This figure shows what happens when 1000 women ages 40, 50, or 60 get annual mammograms for 10 years. It is possible to compare the number of women saved from death from breast cancer with the number of false-positive mammograms or diagnosis with DCIS.

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Cancer Institute

1-800-4-CANCER
(www.nci.nih.gov)
National Comprehensive Cancer Network

(www.nccn.org/patients/patient_gls.asp)
American Cancer Society

1-800-ACS-2345
(www.cancer.org)
National Library of Medicine

(www.nlm.nih.gov/medlineplus/healthtopics.html)
Susan G. Komen Breast Cancer Foundation

(www.komen.org)

Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Chu, KC, Tarone, RE, Kessler, LG, et al. Recent trends in U.S. breast cancer incidence, survival, and mortality rates. J Natl Cancer Inst 1996; 88:1571.
2. Brown, ML, Houn, F, Sickles, EA, et al. Screening mammography in community practice: positive predictive value of abnormal findings and yield of follow-up procedures. AJR Am J Roentgenol 1995; 165:1373.
3. Thomas, DB, Gao, DL, Ray, RM, et al. Randomized trial of breast self-examination in shanghai: final results. J Natl Cancer Inst 2002; 94:1445.
4. Saslow, D, Boetes, C, Burke, W, et al. American Cancer Society guidelines for breast cancer screening with MRI as an adjunct to mammography. CA Cancer J Clin 2007; 57:75.
5. U.S. Preventive Services Task Force. Guide to Clinical Preventive Services, Third Edition. www.ahrq.gov/clinic/uspstfix.htm (Accessed 3/7/05).
6. National Institutes of Health Consensus Development Conference Statement Jan 21-23,1997. 103. Breast cancer screening for women ages 40-49. consensus.nih.gov/cons/103/103_intro.htm (Accessed October 26, 2005).
7. Qaseem, A, Snow, V, Sherif, K, et al. Screening mammography for women 40 to 49 years of age: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2007; 146:511.
8. Humphrey, LL, Helfand, M, Chan, BK, Woolf, SH. Breast cancer screening: A summary of the evidence for the US Preventive Services Task Force. Ann Intern Med 2002; 137:347.

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Friday, October 12, 2007