Endometrial Cancer — What All Women Should Know

Circa 2005

According to the American Cancer Society, each year almost 650,000 American women find out they have cancer; of this group, roughly 84,000 have gynecologic cancers, including cancers of the ovary, endometrium (lining of the uterus), cervix (entrance to the uterus), fallopian tubes, vagina and vulva (external genitalia).

The term uterine cancer generally refers to endometrial cancer, although a small number of women develop cancers of other types of uterine cells, such as muscle cells. Endometrial cancer is the fourth most common cancer in women and the most common gynecologic cancer. It develops when the cells that line the uterus become abnormal and grow uncontrollably, eventually invading surrounding tissue and spreading throughout the body. Forty thousand women in the U.S. are diagnosed with endometrial cancer annually, and the disease is responsible for approximately 6,600 deaths each year. Chances of recovery are greater than 90 percent if the cancer is diagnosed and treated early, but that rate falls precipitously in later stages of illness.

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WHO IS AT RISK FOR ENDOMETRIAL CANCER?

While endometrial cancer can occur in women of any age, in most cases it develops in women who have already gone through menopause. It occurs more frequently in Caucasian women than in African-American, Latina, American Indian or Asian/Pacific Islander women; nevertheless, mortality rates are almost twice as high for African-American women as for women of other races.

Although the exact cause of endometrial cancer is not known, several factors have been shown statistically to increase the risk for its development. Most are thought to operate through greater exposure to the reproductive hormone estrogen, either naturally or from outside sources, particularly when it is not balanced with the hormone progesterone. There are several ways women can be exposed to higher amounts of estrogen. In general, the earlier a woman begins having menstrual cycles and the later she goes through menopause, the more estrogen she is exposed to and the greater her risk. Pregnancy, breastfeeding and birth control pills interrupt this estrogen stimulation and improve the balance with progesterone, thereby reducing the risk of endometrial cancer. Obesity increases the risk because fat tissue converts other hormones to estrogen in the body. Other medical conditions like diabetes and high blood pressure are statistically associated with higher rates of endometrial cancer, but it is thought that the risk may be caused by the increased rates of obesity in these illnesses. The breast cancer drug tamoxifen is structurally similar to estrogen and slightly increases the chances of endometrial cancer; however, the reduction in breast cancer recurrence for women who use this drug far outweighs the risk. Finally, women who choose to take estrogen for uncomfortable menopausal symptoms have a small increase in endometrial cancer risk unless they take progesterone at the same time.

As with many reproductive cancers, a family history of endometrial cancer or related cancers can be important in determining cases of increased risk where extra vigilance is warranted. A small percentage of women who get endometrial cancer carry a genetic mutation causing a syndrome called Lynch Syndrome or hereditary nonpolyposis colorectal cancer syndrome (HNPCC), which is associated with colon and endometrial cancers. In families passing on this mutation, multiple members are usually affected, often before the age of 50. Having a mutation doesn’t necessarily mean a woman is going to get cancer, but it does increase her risk, so women with multiple affected relatives may wish to be tested. Women with the mutation generally choose more rigorous screening; some have undergone prophylactic hysterectomy (preventive removal of the uterus) to decrease the chances of contracting cancer, but this step is controversial. Because the decision to get tested is highly personal, it should be discussed with a doctor who is trained in counseling patients about genetic testing.

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WHAT ARE THE SYMPTOMS?

One of the more frequent—but not universal—symptoms of endometrial cancer is abnormal bleeding. Any new onset bleeding in a post-menopausal woman should immediately prompt an evaluation for endometrial cancer. For pre-menopausal women or peri-menopausal women, endometrial cancer may produce bleeding in between periods or bleeding that is unusually heavy or longlasting. Unfortunately, diagnosis for these younger women is complicated by the fact that many common benign conditions can produce the same symptoms. For instance, this bleeding pattern can be seen with non-cancerous fibroid tumors of the uterus. Roughly a third of all women have received a diagnosis of uterine fibroids, and ultrasound studies show that by age fifty, 70 percent of Caucasian women and 80 percent of African-American women have developed these frequently uncomfortable but relatively harmless tumors.

Other symptoms may include abnormal vaginal discharge, pelvic or back pain, pain with urination or sexual intercourse, or blood in the stool or urine. Nevertheless, all of these symptoms are non-specific and could represent a variety of different conditions.

Because the rate of endometrial cancer increases after age 35, the American College of Obstetricians and Gynecologists currently recommends endometrial evaluation in any woman age 35 or older who has abnormal uterine bleeding. For younger women there is no smoking gun that dictates an evaluation for endometrial cancer, but women with symptoms or risk factors may wish to discuss an evaluation with their doctors.

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WHAT ABOUT SCREENING AND PREVENTION?

Unfortunately, no good tool yet exists to allow accurate, widespread endometrial cancer screening. Therefore, for asymptomatic women without a family history/genetic syndrome, the best way to prevent endometrial cancer is to alter the risk factors they have control over. For instance, women who are overweight can get weight loss assistance, limit animal fats, increase fruits and vegetables and get regular exercise. Women who wish to get pregnant should try to do so before age 30, and all women should consider using methods of birth control, like oral contraceptive pills (OCPs) or depoprovera injections, that provide progesterone balance. Multiple studies have confirmed that OCPs reduce the risk for endometrial cancer—as well as ovarian cancer, ectopic pregnancy, pelvic infections and a host of other gynecologic problems—and that the longer a woman takes them, the greater their preventive effect. Women who are carriers of the gene for Lynch Syndrome need more rigorous screening, with annual endometrial biopsies starting at age 35, but this level of screening has not been shown to be useful for women without the family cancer syndrome.

HOW IS ENDOMETRIAL CANCER DIAGNOSED AND STAGED?

The primary tool in evaluation when endometrial cancer is suspected is an endometrial biopsy, where a thin flexible tube is passed through the vagina and cervix into the uterus and a small amount of the endometrium is removed. The biopsy can be somewhat uncomfortable, but it does not require surgery or anesthesia and can be performed in the gynecologist’s office. Sometimes the endometrial biopsy does not provide enough tissue, and a dilatation and curettage (D&C) procedure is needed. D&Cs are done in the operating room under anesthesia. The doctor dilates the opening to the uterus and then uses a tool called a curette to scrape a sample from the lining.

Many times abnormal bleeding in younger women is first investigated with a transvaginal ultrasound. An ultrasound uses sound waves that bounce off tissues to provide a picture of whatever is being investigated. By inserting an ultrasound probe into the vagina, doctors can get a good visualization of the uterus, the fallopian tubes and the ovaries. A transvaginal ultrasound can identify ovarian abnormalities, uterine fibroid tumors and increased thickness of the endometrium that may indicate a need for biopsy.

To guide treatment and understand prognosis, staging is necessary. Surgical treatment and staging are generally done within the same operation, with a careful inspection of the uterus, other organs in the pelvis and the pelvic lymph nodes. Biopsy specimens are sent to a pathologist while the surgeon is still working, and staging is done according to a system established by the International Federation of Gynecologists and Obstetricians. Stage I cancer is confined to the body of the uterus, without any spread to the cervix; stage II cancer has spread to the cervix but not outside the uterus; stage III cancer has spread outside the uterus, but is confined to the pelvis without involving the bladder or rectum; stage IV cancer has spread to the bladder or rectum or has more distant metastasis (seeding) in other organs. While most aspects of staging are done at surgery, physicians sometimes order additional tests for clarification before or after surgery, such as CT scans or MRIs, a colonoscopy to examine the rectum and colon, or blood tests for cancer markers such as CA-125, which can suggest the presence of cancer outside the uterus. Every person’s case is different, so the combination of tests varies to allow doctors the best information available for planning successful treatment.

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WHAT TREATMENTS ARE AVAILABLE?

Almost all women with endometrial cancer have some type of surgery in the course of treatment, both to stage the cancer and to remove as much of it as possible. Most women undergo a hysterectomy (removal of the uterus) and bilateral salpingo-oophorectomy (removal of both ovaries and fallopian tubes), because there is always a risk of microscopic disease in both of the ovaries and the uterus. In young women who have very early cancer (stage IA), it is sometimes possible to maintain fertility by treating temporarily with other modalities, then remove the uterus and ovaries when child-bearing is finished. For women with stage I and stage II cancers, all visible areas of tumor can generally be removed during surgery. For women with more advanced cancers, even if some tumor remains after surgery, removing as much cancer as possible improves outcomes and can help decrease pain and lessen other symptoms.

Depending on the cancer stage, women with endometrial cancer often receive radiation treatment as well. Radiation therapy uses high energy rays to kill cancer cells and decrease chances that the cancer will come back. Radiation comes either from an external source (external beam radiation) or from an internal source (brachytherapy). External beam radiation requires patients to come in to a radiation treatment center five days a week for up to six or eight weeks. Patients receiving external beam radiation may also be offered brachytherapy (also called intracavitary irradiation), which allows a higher concentration of radiation directly at the tumor bed, providing increased effectiveness while sparing normal tissues. A tube is placed in the vagina, and a small radioactive source is place inside the tube. Various different protocols and techniques for brachytherapy are available, some using higher doses over shorter time periods and some using lower doses over longer time periods. It is important for each woman to get information about the range of radiation therapy options available for her individual case. Radiation treatment can cause the lining of the vagina to thin and may cause light bleeding after intercourse. Use of a dilator helps maintain stretch and minimizes the formation of scar tissue.

Chemotherapy, the use of anti-cancer medications, is reserved for women whose cancers are very advanced or recur after treatment with surgery and radiation. Some of these women may also receive hormone therapy if the pathology examination finds their tumor cells have receptors for estrogen or progesterone.

Women who have been treated for endometrial cancer need to be followed closely for recurrence. The highest risk is in the first three years after diagnosis, and followup during this period involves visits to a cancer specialist several times a year. A variety of monitoring methods may be used, including sampling of vaginal cells, ultrasound, CA-125 levels and/or CT scans, depending on the case. It is important for women to report any symptoms they experience.

Many questions remain unanswered about the best treatment protocols for endometrial cancer and the best ways to help detect it earlier, particularly in women who contract the cancer before menopause. The more women are able to educate themselves about the factors that put them at risk for gynecologic cancers, the symptoms and the methods of detection, the better they will be able to advocate for care that may save their lives.

by Gillian Friedman, MD

Women’s Cancer Network

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