Endometrial cancer develops when the cells that make up the inner lining of the uterus (the endometrium) become abnormal and grow uncontrollably.
Description
Endometrial cancer (also called uterine cancer) is the fourth most common type of cancer among women and the most common gynecologic cancer. Approximately 34, 000 women are diagnosed with endometrial cancer each year. In 1998, approximately 6, 300 women died from this cancer. Although endometrial cancer generally occurs in women who have gone through menopause and are 45 years of age or older, 30% of the women with endometrial cancer are younger than 40 years of age. The average age at diagnosis is 60 years old.
The uterus, or womb, is the hollow female organ that supports the development of the unborn baby during pregnancy. The uterus has a thick muscular wall and an inner lining called the endometrium. The endometrium is very sensitive to hormones and it changes daily during the menstrual cycle. The endometrium is designed to provide an ideal environment for the fertilized egg to implant and begin to grow. If pregnancy does not occur, the endometrium is shed causing the menstrual period.
More than 95% of uterine cancers arise in the endometrium. The most common type of uterine cancer is adenocarcinoma. It arises from an abnormal multiplication of endometrial cells (atypical adenomatous hyper-plasia) and is made up of mature, specialized cells (well-differentiated).
Less commonly, endometrial cancer arises without a preceding hyperplasia and is made up of poorly differentiated cells. The more common of these types are the papillary serous and clear cell carcinomas. Poorly differentiated endometrial cancers are often associated with a less promising prognosis.
Demographics
The highest incidence of endometrial cancer in the United States is in Caucasians, Hawaiians, Japanese, and African Americans. American Indians, Koreans, and Vietnamese have the lowest incidence. African-American and Hawaiian women are more likely to be diagnosed with advanced cancer and, therefore, have a higher risk of dying from the disease.
Causes and symptoms
Although the exact cause of endometrial cancer is unknown, it is clear that high levels of estrogen, when not balanced by progesterone, can lead to abnormal growth of the endometrium. Factors that increase a woman's risk of developing endometrial cancer are:
Age. The risk is considerably higher in women who are over the age of 50 and have gone through menopause.
Obesity. Being overweight is a very strong risk factor for this cancer. Fatty tissue can change other normal body chemicals into estrogen, which can promote endometrial cancer.
Estrogen replacement therapy. Women receiving estrogen supplements after menopause have a 12 times higher risk of getting endometrial cancer if progesterone is not taken simultaneously.
Diabetes. Diabetics have twice the risk of getting this cancer as nondiabetic women. It is not clear if this risk is due to the fact that many diabetics are also obese and hypertensive. One 1998 study found that women who were obese and diabetic were three times more likely to develop endometrial cancer than women who were obese but nondiabetic. This study also found that nonobese diabetics were not at risk of developing endometrial cancer.
Irregular menstrual periods. During the menstrual cycle, there is interaction between the hormones estrogen and progesterone. Women who do not ovulate regularly are exposed to high estrogen levels for longer periods of time. If a woman does not ovulate regularly, this delicate balance is upset and may increase her chances of getting uterine cancer.
Early first menstruation or late menopause. Having the first period at a young age (a 1997 Pediatrics article identified the mean age of menses as 12.16 years in African-American girls and 12.88 years in white girls) or going through menopause at a late age (over age 51 according to a 2001 Prevention article) seem to put women at a slightly higher risk for developing endome-trial cancer.
Tamoxifen. This drug, which is used to treat or prevent breast cancer, increases a woman's chance of developing endometrial cancer. Tamoxifen users tend to have more advanced endometrial cancer with an associated poorer survival rate than those who do not take the drug. In many cases, however, the value of tamoxifen for treating breast cancer and for preventing the cancer from spreading far outweighs the small risk of getting endometrial cancer.
Family history. Some studies suggest that endometrial cancer runs in certain families. Women with inherited mutations in the BRCA1 and BRCA2 genes are at a higher risk of developing breast, ovarian, and other gynecologic cancers. Those with the hereditary nonpolyposis colorectal cancergene have a higher risk of developing endometrial cancer.
Breast, ovarian, or colon cancer. Women who have a history of these other types of cancer are at an increased risk of developing endometrial cancer.
Low parity or nulliparity. Endometrial cancer is more common in women who have born few (low parity) or no (nulliparity) children. The high levels of progesterone produced during pregnancy has a protective effect against endometrial cancer. The results of one study suggest that nulliparity is associated with a lower survival rate.
Polycystic ovary syndrome. The increased level of estrogen associated with this abnormality raises the risk of cancers of the breast and endometrium.
The most common symptom of endometrial cancer is unusual vaginal spotting, bleeding or discharge. In women who are near menopause (perimenopausal), symptoms of endometrial cancer could include bleeding between periods (intermenstrual bleeding), heavy bleeding that lasts for more than seven days, or short menstrual cycles (fewer than 21 days). For women who have gone through menopause, any vaginal bleeding or abnormal discharge is suspect. Pain in the pelvic region and the presence of a lump (mass) are symptoms that occur late in the disease.
Diagnosis
If endometrial cancer is suspected, a series of tests will be conducted to confirm the diagnosis. The first step will involve taking a complete personal and family medical history. A physical examination, which will include a thorough pelvic examination, will also be done.
The doctor may order an endometrial biopsy. This is generally performed in the doctor's office and does not require anesthesia. A thin, flexible tube is inserted through the cervix and into the uterus. A small piece of endometrial tissue is removed. The patient may experience some discomfort, which can be minimized by taking an anti-inflammatory medication (like Advil or Motrin) an hour before the procedure.
If an adequate amount of tissue was not obtained by the endometrial biopsy, or if the biopsy tissue looks abnormal but confirmation is needed, the doctor may perform a dilatation and curettage (D & C). This procedure is done in the outpatient surgery department of a hospital and takes about an hour. The patient may be given general anesthesia. The doctor dilates the cervix and uses a special instrument to scrape tissue from inside the uterus.
The tissue that is obtained from the biopsy or the D & C is sent to a laboratory for examination. If cancer is found, then the type of cancer will be determined. The treatment and prognosis depends on the type and stage of the cancer.
Transvaginal ultrasound may be used to measure the thickness of the endometrium. For this painless procedure, a wand-like ultrasound transducer is inserted into the vagina to enable visualization and measurement of the uterus, the thickness of the uterine lining, and other pelvic organs.
Other possible diagnostic procedures include sonohysterography and hysteroscopy. For sonohysteroscopy, a small tube is passed through the cervix and into the uterus. A small amount of a salt water (saline) solution is injected through the tube to open the space within the uterus and allow ultrasound visualization of the endometrium. For hysteroscopy, a wand-like camera is passed through the cervix to allow direct visualization of the endometrium. Both of these procedures cause discomfort, which may be reduced by taking an anti-inflammatory medication prior to the procedure.
Treatment team
The treatment team for endometrial cancer may include a gynecologist, gynecologic oncologist, surgeon, radiation oncologist, gynecologic nurse oncologist, sexual
therapist, psychiatrist, psychological counselor, and social worker.
Clinical staging, treatments, and prognosis
Clinical staging
The International Federation of Gynecology and Obstetrics (FIGO) has adopted a staging system for endometrial cancer. The stage of cancer is determined after surgery. Endometrial cancer is categorized into four stages (I, II, III, and IV) which are subdivided (A, B, and possibly C) based on the depth or spread of cancerous tissue. Seventy percent of all uterine cancers are stage I, 10% to 15% are stage II, and the remainder are stages III and IV. The cancer is also graded (G1, G2, and G3) based upon microscopic analysis of the aggressiveness of the cancer cells.
The FIGO stages for endometrial cancer are:
Stage I. Cancer is limited to the uterus.
Stage II. Cancer involves the uterus and cervix.
Stage III. Cancer has spread out of the uterus but is restricted to the pelvic region.
Stage IV. Cancer has spread to the bladder, bowel, or other distant locations.
Treatments
The mainstay of treatment for most stages of endometrial cancer is surgery. Radiation therapy, hormonal therapy, and chemotherapy are additional treatments (called adjuvant therapy). The necessity of adjuvant therapy is a controversial topic which should be discussed with the patient's treatment team.
SURGERY.
Most women with endometrial cancer, except those with stage IV disease, are treated with hysterectomy. A simple hysterectomy involves the removal of the uterus. In a bilateral salpingo-oophorectomy with total hysterectomy, the ovaries, fallopian tubes, and uterus are removed. This may be necessary because endometrial cancer often spreads to the ovaries first. The lymph nodes in the pelvic region may also be biopsied or removed to check for metastasis. Hysterectomy is traditionally performed through an incision in the abdomen (laparotomy), however, endoscopic surgery (laparoscopy) with vaginal hysterectomy is also being used. Women with stage I disease may require no further treatment. However, those with higher grade disease will receive adjuvant therapy.
RADIATION THERAPY.
The decision to use radiation therapy depends on the stage of the disease. Radiation therapy may be used before surgery (preoperatively) and/or after surgery (postoperatively). Radiation given from a machine that is outside the body is called external radiation therapy. Sometimes applicators containing radioactive compounds are placed inside the vagina or uterus. This is called internal radiation therapy or brachytherapy and requires hospitalization.
Side effects are common with radiation therapy. The skin in the treated area may become red and dry. Fatigue, upset stomach, diarrhea, and nausea are also common complaints. Radiation therapy in the pelvic area may cause the vagina to become narrow (vaginal stenosis), making intercourse painful. Premature menopause and some problems with urination may also occur.
CHEMOTHERAPY.
Chemotherapy is usually reserved for women with stage IV or recurrent disease because this therapy is not a very effective treatment for endome-trial cancer. The anticancer drugs are given by mouth or intravenously. Side effects include stomach upset, vomiting, appetite loss (anorexia), hair loss (alopecia), mouth or vaginal sores, fatigue, menstrual cycle changes, and premature menopause. There is also an increased chance of infections.
HORMONAL THERAPY.
Hormonal therapy uses drugs like progesterone to slow the growth of endometrial
cells. These drugs are usually available as pills. This therapy is usually reserved for women with advanced or recurrent disease. Side effects include fatigue, fluid retention, and appetite and weight changes.
Prognosis
Because it is possible to detect endometrial cancer early, the chances of curing it are excellent. The five year survival rates for endometrial cancer by stage are: 90%, stage I; 60%, stage II; 40%, stage III; and 5%, stage IV. Endometrial cancer most often spreads to the lungs, liver, bones, brain, vagina, and certain lymph nodes.
Alternative and complementary therapies
Although alternative and complementary therapies are used by many cancer patients, very few controlled studies on the effectiveness of such therapies exist. Mind-body techniques such as prayer, biofeedback, visualization, meditation, and yoga, have not shown any effect in reducing cancer but they can reduce stress and lessen some of the side effects of cancer treatments. Clinical studies of hydrazine sulfate found that it had no effect on cancer and even worsened the health and well-being of the study subjects. One clinical study of the drug amygdalin (Laetrile) found that it had no effect on cancer. Laetrile can be toxic and has caused deaths. Shark cartilage, although highly touted as an effective cancer treatment, is an improbable therapy that has not been the subject of clinical study.
The American Cancer Society has found that the "metabolic diets" pose serious risk to the patient. The effectiveness of the macrobiotic, Gerson, and Kelley diets and the Manner metabolic therapy has not been scientifically proven. The FDA was unable to substantiate the anti-cancer claims made about the popular Cancell treatment.
There is no evidence for the effectiveness of most over-the-counter herbal cancer remedies. Some herbals have shown an anticancer effect. As shown in clinical studies, Polysaccharide krestin, from the mushroom Coriolus versicolor, has significant effectiveness against cancer. In a small study, the green alga Chlorella pyrenoidosa has been shown to have anticancer activity. In a few small studies, evening primrose oil has shown some benefit in the treatment of cancer.
For more comprehensive information, the patient should consult the book on complementary and alternative medicine published by the American Cancer Society listed in the Resources section.
Coping with cancer treatment
The patient should consult her treatment team regarding any side effects or complications of treatment. Vaginal stenosis can be prevented and treated by vaginal dilators, gentle douching, and sexual intercourse. A water-soluble lubricant may be used to make sexual intercourse more comfortable. Many of the side effects of chemotherapy can be relieved by medications. Women should consult a psychotherapist and/or join a support group to deal with the emotional consequences of cancer and hysterectomy.
Clinical trials
Because endometrial cancer is a common type of cancer there are many studies underway to optimize its treatment. Women should consult with their treatment team to determine if they are candidates for any ongoing studies.
Prevention
Women (especially postmenopausal women) should report any abnormal vaginal bleeding or discharge to the doctor. Controlling obesity, blood pressure, and diabetes can help to reduce the risk of this disease. Women on estrogen replacement therapy have a substantially reduced risk of endometrial cancer if progestins are taken simultaneously. Long-term use of birth control pills has been shown to reduce the risk of this cancer. Women who have irregular periods may be prescribed birth control pills to help prevent endometrial cancer. Women who are taking tamoxifen and those who carry the hereditary nonpolyposis colorectal cancergene should be screened regularly, receiving annual pelvic examinations.
Special concerns
Of special concern to the young woman with endometrial cancer is the impact that a hysterectomy will have on her fertility, sexuality, and body image. Depression is common. Symptoms caused by the sudden onset of menopause, due to removal of the ovaries, can be more severe than with natural menopause. Estrogen replacement therapy is not commonly used due to the potential risk of cancer recurrence. Without estrogen replacement, osteoporosis becomes a concern and calcium supplements should be considered. Weight bearing exercise and alendronate (Fosamax) will also decrease the development rate of osteoporosis. Vaginal stenosis following radiation treatment is a concern.
Resources
BOOKS
Bruss, Katherine, Christina Salter, and Esmeralda Galan, eds. American Cancer Society's Guide to Complementary and Alternative Cancer Methods. Atlanta: American Cancer Society, 2000.
Burke, Thomas, Patricia Eifel, and Muggia Franco. "Cancers of the Uterine Body." In Cancer: Principles & Practice of Oncology, ed. Vincent DeVita, Samuel Hellman, and Steven Rosenberg. Philadelphia: Lippincott Williams & Wilkins, 2001, pp.1573- 86.
Long, Harry. "Carcinoma of the Endometrium." In Current Therapy in Cancer, ed. John Foley, Julie Vose, and James Armitage. Philadelphia: W. B. Saunders Company, 1999, pp.162-66.
Primack, Aron. "Complementary/Alternative Therapies in the Prevention and Treatment of Cancer." In Complementary/Alternative Medicine: An Evidence-Based Approach, ed. John Spencer and Joseph Jacobs. St. Louis: Mosby, 1999, pp.123-69.
PERIODICALS
Bristow, Robert. "Endometrial Cancer." Current Opinion in Oncology 11 (September 1999): 388- 393.
Canavan, Timothy and Nipa Doshi. "Endometrial Cancer." American Family Physician 59 (June 1999): 3069-3077.
Elit, Laurie. "Endometrial Cancer: Prevention, Detection, Management, and Follow up." Canadian Family Physician 46 (April 2000): 887-892.
Hogberg, Thomas, Margareta Fredstorp, and Anuja Jhingran. "Indications for Adjuvant Radiotherapy in Endometrial Carcinoma." Hematology/Oncology Clinics of North America: Current Therapeutic Issues in Gynecologic Cancer 13 (February 1999): 189- 209.
ORGANIZATIONS
American Cancer Society, National Headquarters. 1599 Clifton Rd. NE, Atlanta, GA 30329. (800) 227-2345. <http://www.cancer.org/>.
Cancer Research Institute, National Headquarters. 681 Fifth Ave., New York, NY 10022. (800) 992-2623. <http://www.cancerresearch.org>.
Gynecologic Cancer Foundation. 401 North Michigan Ave., Chicago, IL 60611. (800) 444-4441. <http://www.wcn.org>.
National Cancer Institute, National Institutes of Health. 9000 Rockville Pike, Bethesda, MD 20892. (800) 422-6237. <http://cancernet.nci.nih.gov/>.
—A treatment done when there is no evidence of residual cancer in order to aid the primary treatment. Adjuvant treatments for endome-trial cancer are radiation therapy, chemotherapy, and hormone therapy.
Atypical adenomatous hyperplasia
—The over-growth of the endometrium. This precancerous condition is estimated to progress to cancer in one third of the cases.
Dilation and curettage (D & C)
—A procedure in which the doctor opens the cervix and uses a special instrument to scrape tissue from the inside of the uterus.
Endometrial biopsy
—A procedure in which a sample of the endometrium is removed and examined under a microscope.
Endometrium
—The mucosal layer lining the inner cavity of the uterus. The endometrium's structure changes with age and with the menstrual cycle.
Estrogen
—A female hormone responsible for stimulating the development and maintenance of female secondary sexual characteristics.
Estrogen replacement therapy (ERT)
—A treatment in which estrogen is used therapeutically during menopause to alleviate certain symptoms such as hot flashes. ERT has also been shown to reduce the risk of osteoporosis and heart disease in women.
Progesterone
—A female hormone that acts on the inner lining of the uterus and prepares it for implantation of the fertilized egg.
Progestins
—A female hormone, like progesterone, that acts on the inner lining of the uterus.
QUESTIONS TO ASK THE DOCTOR
What type of cancer do I have?
What stage of cancer do I have?
What is the 5-year survival rate for women with this type of cancer?
Has the cancer spread? What tests will be used to determine this?
What are my treatment options?
Is adjuvant therapy really necessary in my case?
What are the risks and side effects of these treatments?
What medications can I take to relieve treatment side effects?
Are there any clinical studies underway that would be appropriate for me?
What effective alternative or complementary treatments are available for this type of cancer?
How debilitating is the treatment? Will I be able to continue working?
How will the treatment affect my sexuality?
Are there any restrictions regarding sexual activity?
