What a Menstrual Problem Could Mean

here's no way around it: Endometrial cancer is a dreaded, potentially lethal disease. Still, there is plenty of reason for optimism. If the cancer is caught soon enough—before it's had a chance to spread beyond the uterus—the odds of a cure are excellent. Eight out of 10 women treated at this stage of the disease can expect to go on with their lives for a minimum of 5 years. And happily, 3 out of 4 cases are discovered at this early, curable stage.

But make no mistake about it: The key word here is “early.” Keeping alert for the first signs of a problem is your best guarantee of successful treatment and long­term survival.

The telltale sign to watch for, as with so many other diseases of the reproductive system, is abnormal bleeding from the vagina. But what, exactly, does “abnormal” bleeding mean?

In this instance, what we're talking about is a relatively unalarming watery discharge that begins with some streaks of blood and may contain more blood later on. This symptom may seem somewhat vague, but that's no reason to dismiss it. When a woman encounters this problem, she should see a physician promptly, especially if she is entering or past menopause, when her menstrual periods end.

After menopause, when normal bleeding has stopped, any bleeding is considered “abnormal.” And cancer of the endometrium—the lining of the uterus—appears most often around or after menopause. So any irregular bleeding in a woman entering, or about to enter, menopause is not a routine matter. Approximately 25 percent of postmenopausal bleeding is due to some form of cancer of the uterus.

Endometrial cancer, however, can begin with no symptoms. If the disease progresses unnoticed to a more advanced stage, the first warning sign could be pelvic pain or pressure as fluid accumulates in the abdomen. Fortunately, it is usually discovered before reaching this point.

What is Endometrial Cancer?

Cancer is abnormal tissue growth brought about by uncontrolled division of the cells that make it up. In endometrial cancer the tissue involved is the inner lining of the uterus. When communication and interdependence break down among the cells of this lining, new cells develop faster than existing ones die. The excess cells continue trying to create tissue and perform their normal tasks, but have neither the room nor the regulation to do it properly.

Without order, they multiply, pile up, and eventually form excess tissue that has no function except to grow. As the tissue increases, it forms tissue masses, known as tumors. Some are benign (noncancerous), some malignant (cancerous). Cancerous tumors can destroy normal uterine tissue and break away to spread from one organ to another, invading other parts of the body. This spreading is called metastasis.

Endometrial cancer is one of two major cancers that occur in the uterus. In 3 out of 4 cases, it first develops in the glandular cells of the lining. Later, it may affect their supporting structure known as the stroma. If it spreads, it usually moves into the wall of the uterus, the myometrium. Further growth can project it into the cervix at the mouth of the uterus, and the bladder, bowel, and lower abdominal cavity. The lymph and blood systems may also circulate it to more distant areas of the body, such as the lung or the liver.

An entirely different form of uterine cancer called sarcoma begins in the smooth muscle of the uterine wall. It grows rapidly and may eventually reach the endometrium to involve the surface cells of the uterine lining. While sarcoma presently accounts for only about 5 percent of uterine cancer, its diagnosis is becoming more frequent. (See the nearby box on “Other Cancers of the Uterus.”)

WHERE UTERINE CANCER BEGINS

In nearly three-quarters of all cases, uterine cancer establishes its initial foothold in the glandular cells that line the surface of the endometrium. Uncontrolled multiplication of these cells leads first to hyperplasia—an excessive number of cells—then to tumors formed by a large mass of abnormal cells. If an endometrial tumor is cancerous, it will penetrate deep into the uterine wall, destroying normal tissue as it goes and eventually spreading to nearby organs. A totally unrelated type of tumor arises deep within the muscular wall of the uterus, reaching the endometrium at the surface only in its later stages. Called a sarcoma, this tumor spreads more quickly than endometrial cancer and is therefore more dangerous. Fortunately, it is also quite rare, accounting for only 1 uterine cancer in 20.

Distinct from endometrial cancer are the benign tumors known as fibroids. These abnormal growths seldom cause pain, but can become large enough to be uncomfortable as they press on organs around the uterus and eventually produce bleeding. They do not usually invade nearby tissues or organs, however, and can be removed surgically. (For more information, see Chapter 7, “Your Treatment Options for Fibroids.”)

Benign or Malignant?

Endometrial hyperplasia—an abnormal increase in the cells of the endometrium—is common among women who are nearing menopause and who seldom ovulate. It is not in itself cancerous, but can change progressively to become malignant.

Since it can be a forerunner of endometrial cancer, your doctor will investigate it carefully once it's discovered. Treatment—or lack of it—depends on which of three classes of hyperplasia is identified:

• Cystic hyperplasia is generally considered unlikely to become malignant, but will be monitored regularly.
• Adenomatous hyperplasia is likely to progress to cancer in 25 percent of women who develop it, and generally requires some type of treatment.
• Atypical hyperplasia is more serious yet, and may call for surgical removal of the uterus.

Endometrial cancer itself is broken down into four classifications: adenocarcinoma, adenosquamous carcinoma, papillary serous carcinoma, and clear cell carcinoma. Adenocarcinoma accounts for 3 of 4 cases of endometrial cancer. Fortunately, it is the easiest to treat, with the best chance of success.

Risks, Large and Small

As with most other cancers, how and why endometrial cancer develops is still an unsolved mystery. Because the most common variety, adenocarcinoma, appears far more frequently at and after menopause, usually in women in their 60s and 70s, it is considered a slow­growing cancer. The chances of developing it are greater for women who:

• Began to menstruate at an early age
• Went through menopause late (after the age of 53)
• Are considerably overweight
• Never had a child

While endometrial disease is not inherited, there is a tendency for it to appear more often in relatives. Women who develop ovarian tumors, which stimulate estrogen production, are also at higher risk, as are women with endometrial hyperplasia.

The Role of Excess Weight

Diabetes and/or high blood pressure are also common in those who develop endometrial cancer, but the excess weight that accompanies these problems is probably the factor at work. Women who are 50 pounds overweight are 9 times as likely to develop the disease as women of normal weight. Excess fatty tissue turns certain hormones into a form of estrogen, and women with high levels of estrogen are twice as likely to develop endometrial cancer.

Estrogen and Increased Risk

Heavy use of estrogen replacement therapy (ERT) is clearly a factor in the development of endometrial cancer in some women. This is especially true if the estrogen is not combined with progesterone, or a similar compound called progestin. Estrogen and progesterone are important controls in the reproductive cycle. Until menopause, estrogen stimulates a build­up of the endometrium to accept a woman's egg, then prompts it to shed the excess

tissue if conception does not take place. When estrogen levels decline after menopause, a woman faces problems ranging from depression and “hot flashes” to increased risk of coronary heart disease and osteoporosis (brittle and easily broken bones). ERT overcomes these effects, but it can also stimulate the endometrium to bleed and can increase the likelihood of endometrial hyperplasia, which in turn can progress to adenocarcinoma. To reduce this risk, doctors often supplement ERT with progestin treatment, which has been demonstrated to reverse endometrial hyperplasia.

Other Risk Factors

A history of certain other diseases also increases the chances of developing endometrial cancer. Polycystic ovarian disease, ovarian tumor, or colon or rectal cancer are among the culprits. Women who have had breast cancer are more prone to develop endometrial cancer; and the breast-cancerdrug tamoxifen has also been linked to an increased risk of endometrial disease. In fact, any history of cancer of a woman's reproductive organs increases the risk. Additionally, in the under 40 age group, this disease occurs 3 times as often in women with endometriosis, a disease of abnormal endometrial tissue development outside the uterus.

You can see that hormone levels affect many of these risk factors in some way. Nevertheless, it is unlikely that any single factor triggers the disease. In fact, 2 in 5 cases of endometrial cancer appear to have no connection to abnormal functioning of the system that produces the hormones.

When Does It Strike?

Endometrial cancer is diagnosed in nearly 40,000 women annually in the United States. It represents 6 percent of all cancers in women. It occurs more often than any other cancer of the reproductive tract, now exceeding cervical cancer, which for most of this century ranked number one.

Unlike endometriosis, which affects women almost entirely in their childbearing years, endometrial cancer occurs overwhelmingly in women who have reached or are reaching menopause. Three of 4 women with the disease are postmenopausal. Of these, the majority are between 61 and 75. Overall, it is

most often diagnosed in women who are between 55 and 60 years of age.

As our population ages, the number of endometrial cancer cases is increasing. However, fatalities from endometrial cancer are not keeping pace. In 1990, when 40,000 cases were diagnosed, only 4,000 women succumbed to the disease. By comparison, cervical cancer was diagnosed in only 13,500 women that year, but took the lives of 6,000. Overall, the mortality rate from endometrial cancer is now about 3 women in 100,000.

Endometrial cancer's lower death rate—despite its higher incidence—is primarily a result of early detection. Because bleeding usually provides a clear warning early in the disease, the cancer can be caught while it is still confined to the uterus. At this early stage, it is the easiest cancer to treat outside of skin cancer.

Stages Of Development

Endometrial cancer can progress through five stages, from tissue abnormalities like hyperplasia to cancer extended to the bladder, bowel, or other parts of the body. Among its targets as the cancer spreads are the wall of the uterus (called the myometrium), the cervix and vagina, the nearby lymph nodes, the bladder, the bowel, the abdominal cavity, and even more distant organs and lymph nodes. The fact that cancer spreads to distant areas of the body by way of the lymphatic system has focused a lot of attention in recent years on carefully checking the lymph nodes near the uterus and cervix, since seemingly unaffected nodes can still spread the malignancy.

If endometrial cancer does recur, it is likely to happen quickly. In 8 out of 10 women who have a recurrence, the new cancer develops in the first 2 years after the first was found and treated. The recurrence is usually in some organ distant from the uterus, due to metastasis by a cancer cell that was not destroyed or removed in the original treatment.

What Can You Do?

Though there is nothing you can do to treat endometrial cancer yourself, if you are aware of the early warning signs and know your degree of risk, you can certainly help prevent, or at the least, detect the disease. Make a list of your family risk factors. Do you, for example, have a close rel-

ative who developed cancer of the reproductive organs or breast? This information can help a doctor evaluate your risk. Take a look at the other risk factors discussed above, and add any to your list that apply to you. If you have diabetes and/or high blood pressure or if you are seriously overweight, get these factors under control with medication and diet.

If you are using estrogen replacement therapy, be sure you know how much you are taking. Have regular checkups by a physi-

cian. If you are a premenopausal woman who has several cancer risk factors, your physician may prescribe oral contraceptives to reduce the danger.

Above all, do not believe any old wives' tales about endometrial cancer—that it is a benign disease or that its spread to lymph nodes is not important. This disease is not benign. It is true that the 5­year survival rate is 8 out of 10 for women treated before the cancer has had a chance to spread beyond the uterus. Nevertheless, 1 in 4 women who have endometrial cancer eventually die from it.

Diagnosis: Difficult but Crucial

Accurate diagnosis must (1) differentiate endometrial cancer from other possible illnesses; (2) locate the particular cancer type; and (3) judge how far the disease has progressed. When you consider that benign conditions—fibroid tumors, endometrial hyperplasia, and the start of normal menopause—all produce symptoms similar to early cancer, and also consider that several other cancers of the uterus progress more rapidly than endometrial cancer, it is obvious that diagnosis is not easy.

The Examination

To begin with, the doctor will take a woman's medical history and review her symptoms. Next is a complete physical exam of the pelvis—the uterus, ovaries, fallopian tubes, vagina, bladder, and rectum. This allows the physician to evaluate the source of the bleeding and the condition of nearby organs that could likely affect or be affected by the uterus. Later, if endometrial cancer is found, the information obtained will help determine whether it has progressed. The doctor will also order routine blood and urine tests. Occasionally, if a woman is too frail or too

overweight for a routine examination, the doctor may use ultrasound to picture the inside of the uterus.

Taking a Biopsy

All other tests aside, the key to a definitive diagnosis is laboratory examination of a sample of endometrial tissue to check for abnormal cells. This procedure of removing and examining tissue is called biopsy. There are many ways of collecting the sample. Irrigation, suction, or brush techniques are all possibilities though they may not obtain enough tissue, and occasionally miss cancer cells or misidentify normal cells as cancerous. The PAP smear, used to detect cancer of the cervix, is accurate only half the time in identifying endometrial cancer, primarily because abnormal endometrial cells lose the features that clearly mark them by the time they reach the cervix, where the PAP smear is collected. Even the well­known dilation and curettage usually referred to as a D&C, in which the uterus is scraped or tissue snipped out while the woman is under anesthesia, can sometimes miss the diagnosis.

One newer alternative to a D&C is diagnostic hysteroscopy, in which a light­bearing telescope is inserted into the uterus so the physician can view the entire cavity and the surface of the endometrium. It is an outpatient procedure that requires a local anesthetic and lasts only a few minutes. Using this technique, the doctor is able to select specific tissue for removal and analysis.

Examining the Tissue

Once a biopsy is obtained, a pathologist examines the cellular make­up of the tissue to determine if it contains cancerous cells.

WHAT TO EXPECT FROM A “D&C”

The “D” portion of this procedure is dilation—opening up the cervix to permit access to the uterus. “C” stands for curettage, or scraping tissue samples from the surface of the endometrial lining of the uterus. To maintain a clear entry to the uterus, the doctor uses a speculum to brace open the walls of the vagina, and a tenaculum to hold back the lips of the cervix. A D&C helps in diagnosing endometrial cancer, but surgery is needed for a cure.

The pathologist decides what kind they are and what their stage of development is. The less­defined each cell and the more the cancer looks like a solid mass of cells instead of normal endometrial cells, the more severe the cancer is likely to be.

Other Tests

Prior to an operation, the biopsy is sometimes followed by more comprehensive testing. The doctor may decide to measure the size, location, and density of tumors with computed axial tomography, the so­called CAT scan. It can also show if the cancer has spread beyond the uterus into the pelvic lymph nodes. Intravenous pyelography (a type of x-ray) locates growths in the urinary tract. Magnetic resonance imaging or MRI supplies cross­sectional images of internal organs.

In addition, the tumor cells may be examined to determine their ability to accept progestin. If the cancer is due to overstimulation by estrogen, taking opposing progestin may become part of the treatment. Overall, comprehensive diagnosis takes less time than it might seem since many tests are conducted at the same time. A basic yes or no can often be given after the first visit to the doctor. From these diagnostic procedures, he or she can tailor a treatment plan to suit the woman and her disease.

Treatment Choices

The stage of the cancer's development is the key consideration in selecting a treatment. The decision is affected by both the degree to which the cancer has penetrated the wall of the uterus and the extent to which it has spread beyond it.

If a younger woman with a 0 stage malignancy (see the box on “Stages of Endometrial Cancer”) wants to keep her ability to have children, she may simply have a D&C com-

bined with progestin treatment. However, a hysterectomy or removal of the uterus before cancer has spread beyond it is the treatment most likely to produce a cure. For a postmenopausal woman, it may be combined with removal of the ovaries and fallopian tubes. There may be more extensive surgery to remove various lymph nodes if the disease has spread or was not diagnosed until it reached an advanced stage. Radiation therapy is another possibility. It may be given both internally and externally. Sometimes it begins before surgery and is resumed afterwards. In other cases, it may not start until after the original surgery. Radiation is used more frequently for advanced stages of cancer.

Chemotherapy is primarily a palliative, a means of reducing the effects of endometrial cancer and prolonging survival. It does not cure the cancer, and is more likely to become part of the treatment in the more advanced stages.

Hysterectomy

A successful hysterectomy—which requires 2 to 3 hours under general anesthesia—removes all cancerous tissue without spreading cancer cells to other tissues and organs. During the operation, the surgeon removes the uterus either through an incision in the lower abdomen or at the top of the vagina. Any suspicious tissue outside the uterus is also taken out and samples of tissue and fluid from the entire pelvic area are taken and analyzed for any cancerous cells. Both ovaries and fallopian tubes are also usually removed, so that the estrogen they produce can pose no further threat of stimulating new cancer.

Effects of Hysterectomy. The effects of a hysterectomy accompanied by removal of the ovaries include depression—even in women past menopause—as well as increased risk of coronary heart disease and osteoporosis. Getting out of bed and walking may be a little difficult the day after surgery, but it is important to try. Vaginal bleeding and discharge for a day or two is not unusual. While it will probably be possible to go home in 4 to 7 days, convalescence may last several weeks. Depending on the particular patient and the stage the cancer had reached, the physician may start her on estrogen replacement therapy within weeks or months with progestins prescribed to balance the estrogen. Follow-up visits to the doctor will be necessary every three to four months.

HOW HYSTEROSCOPY WORKS

A relatively new device called the hysteroscope allows doctors to do a direct visual examination of the endometrium. The lighted tip of the instrument is inserted through the vagina and cervix into the uterine cavity. There the doctor can inspect any abnormal tissues and, using a tiny electrified loop, can even take samples for later lab analysis.

Radiation Therapy.

The need to avoid vital organs and systems while removing cancerous tissue limits the extent of any surgery. Radiation thus takes on a bigger role in treatment of more advanced cancer that has spread beyond the uterus. However, it may also be used in early stages to destroy cancerous cells that are difficult for the surgeon to see or reach, and has even been used alone in some early­stage patients. (Success rates, however, are not as good.) There are two ways of administering the radiation. When treatment is from the outside, an x­ray machine aims a radiation beam at the pelvis, reaching the uterus, cervix, and pelvic lymph nodes. The external treatment usually is given once a day for 4 to 5 weeks. In internal radiation, a number of tiny metal cylinders containing the radioactive elements radium or cesium are implanted in the uterus for a few days.

Radiation will also successfully treat cancer in the peritoneum (the covering of the pelvic organs) or in the ovaries or vagina. At higher stages of cancer development, the doctor may use both internal and external radiation. It is often combined with hormones and chemotherapy to reach the areas to which the cancer has spread.

Experimental Treatments

Immunotherapy is being investigated in a number of clinical trials although it is not yet an accepted form of treatment. Immunotherapy may fight cancer in a variety of ways:

• Strengthening the body's immune system to resist cancer
• Eliminating or suppressing body reactions that allow cancer to grow
• Sensitizing a cancer cell so it is more easily destroyed

Also under study are biological response modifiers, natural substances the body makes to fight cancer, that have now been manufactured in the laboratory. Currently, they are being tested only in endometrial cancer patients whose disease is severe or has recurred.

Chemotherapy

Many drugs used in breast cancer treatment are also used to fight endometrial cancer. They may slow progression of the disease, causing tumors to shrink, but rarely provide a cure. They are used to reach areas not accessible through surgery with more precision than radiation affords. If a woman's individual profile suggests she may respond to several of them, the doctor may prescribe a combination.

Doxorubicin (Adriamycin, Ribex) is an antibiotic that has been in use for some time to fight widespread cancer growth.

Cyclophosphamide (Cytoxan) and cisplatin (Platinol) are injected to break up cancer cell development. They act on new cancer growths in endometrial, ovarian, and bladder cancer, and are often given together. Several studies have shown that half the patients with widespread cancer will respond to a combination of these two drugs and doxorubicin.

Mesna (Mesnex) and ifosfamide (Ifex) are used in treatment of advanced endometrial cancer on a small scale. They are injected together because Mesnex prevents the urinary tract inflammation produced by Ifex.

Tamoxifen , which has been used for almost 20 years to treat advanced breast cancer, is now under study for prevention of breast cancer, as well as for use against some endometrial cancers. Unfortunately, in several trials women treated for advanced breast cancer at the usual tamoxifen dosage had double the risk of developing endometrial cancer. That risk is the same as a woman on estrogen. Although tamoxifen, taken by mouth, appears to work against estrogen's promotion of breast cancer cell growth, it acts like estrogen in other systems of the body.

Hormonal Treatments

Megesterol (Megace) is a progestin taken by mouth to treat severe, widespread endometrial cancer. It balances or reduces any estrogen buildup that promotes tumor growth. Progesterone­based medroxyprogesterone (Amen, Cycrin, Depo­Provera, others) and hydroxyprogesterone do the same. Depo­Provera is given by injection; the others can be taken orally. In the type of endometrial cancer related to estrogen overstimulation and endometrial hyperplasia, where the disease is at stages 0 or I (see the box on “Stages of Endometrial Cancer”), this progestin treatment has stopped or reversed tumor growth. It may even allow women past menopause to begin or continue estrogen therapy as long as they have regular checkups.

Disease and Treatment Damage

Since radiation and chemotherapy affect normal cells as well as cancer cells, side effects are often severe. Chemotherapy may suppress bone marrow, from which blood cells are formed, and thereby cause anemia. Nausea and vomiting, resulting in loss of fluids, can cause kidney problems. Another

effect is inflammation of the inside of the mouth. In a few patients, urinary and rectal inflammation and fistulas (abnormal passages between organs) may show up months and even years after radiation. If the disease reaches a late stage, with cancerous growths in many areas of the body, the side effects of treatment added to the effects of the disease, can become nearly intolerable. However, doctors now have a number of strategies that help make therapy much more comfortable:

• Combining treatments
• Adding drugs that combat side effects
• Using lowest effective dosages
• Limiting radiation or drug therapy for certain patients

Any woman suffering from endometrial cancer and the effects of treatment needs a great deal of emotional and medical support. For sources of emotional and social assistance, see the “Directory of Support Groups” at the end of this book. For relief of physical pain and discomfort, the doctor can draw on a wide variety of medications and therapeutic techniques.

Pain Relief

Pain relievers—both narcotic and non­narcotic—are standard treatment for advanced endometrial cancer. Most frequently used are narcotic medications such as codeine, meperidine (Demerol), oxycodone (Percodan), and, particularly, morphine. If oral forms of these drugs cause nausea or vomiting, the doctor will prescribe injectable and suppository forms instead. For pain caused by pressure on nerves, transcutaneous (through the skin) electric nerve stimulation, called “TENS,” often gives relief.

The woman under treatment and her medical team must be continually alert to the adverse effects, of the more powerful painkillers. Other medications that help are antidepressants, tranquilizers, anti­inflammatory drugs, sedatives, and antinausea medications. The choice of medicines depends on the individual patient's problems.

Prospect for Recovery?

As long as cancer has failed to spread beyond the uterus, the outlook is encouraging. And since this depends on early recognition, prompt diagnosis is crucial. If you have abnormal vaginal bleeding, your doctor must take great care to establish the cause. The biopsy stage of the process is especially

important, since it's the step that determines whether there is a cancer, a benign tumor, or a forerunner of cancer.

Once you've been treated, the most important step you can take is getting regular follow­up care. The danger that some of the cancer was missed is, unfortunately, always a reality. As with any disease, thorough checkups are your best insurance for complete, long­lasting recovery.