Endometrial: The Most Common Reproductive Cancer in Women

Everything you should know, from symptoms to risk factors to treatment, about the uterine cancer that claims thousands every year.

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The most common form of cancer of the female reproductive tract in the United States is endometrial carcinoma -- cancer of the lining of the uterus, or endometrium. Endometrial cancer accounts for over 95 percent of uterine cancers, which themselves represented approximately six percent of all cancers diagnosed among U.S. women in 2010. It is estimated that 46,470 women will be diagnosed with uterine cancer and that 8,120 will die of this disease in 2011. The median age at which women are diagnosed with endometrial cancer is 63.

Traditionally, women with endometrial cancers have been divided into two groups, depending on the form of cancer they have. Type I tumors are estrogen-dependent, meaning their growth is stimulated by estrogen, like some breast cancers. Usually women with Type I tumors are younger and have a better prognosis. Type II tumors account for 10-20 percent of all spontaneously occurring endometrial cancers (those without a family history). The prognosis for Type II tumors, unfortunately, tends to be poor.

In this article, we discuss the risk factors, symptoms, diagnosis, and treatment options for endometrial cancer. We also go over syndromes that are associated with a higher risk of endometrial cancer, like Lynch syndrome and Cowden syndrome, which also increase one's risk of other forms of cancer, including breast, ovarian, thyroid, and intestinal. As doctors learn more and more about the genetics and behavior of endometrial cancer, they are better equipped to determine one's risk of endometrial cancer, diagnose it earlier, and develop more effective means of treatment.

RISK FACTORS

The risk factors for Type I endometrial cancer include obesity, diabetes, high blood pressure, taking medications like Tamoxifen (a breast cancer medication), estrogen replacement therapy without progesterone, chronic anovulation (lack of periods), never being pregnant, late menopause, and genetics.

Patients with Type II endometrial carcinomas are usually older when they are diagnosed and they typically haven't had estrogen replacement therapy. The risk factors for Type II tumors are not as well defined as those of Type I endometrial carcinomas. The fact that Type II tumors are less common makes this cancer type more challenging for doctors to study and characterize. Several studies have reported that Type II cases are more likely to occur in older, normal weight women, and those who have been pregnant multiple times or African American women.

THE SYMPTOMS OF ENDOMETRIAL CANCER

A case history illustrates the risk factors and the symptoms associated with endometrial cancer:

A 45-year-old female who had been pregnant twice and given birth to one child came to her primary care physician complaining of worsening and excessive bleeding for the last six months. Five years earlier she had had her tubes tied in order to prevent further pregnancies. In the last 10 years, the patient had gained weight, her BMI increasing from 29 to 37 (normal is 18.5-24.9), and she developed type II diabetes and high blood pressure.

Upon reviewing her family history, her doctor learns that the patient had family members with cancer: her brother was diagnosed with colon cancer at the age of 47, and her mother was diagnosed with colon cancer at the age of 44. In addition, the patient's sister and maternal aunt were diagnosed with ovarian and endometrial cancer at the ages of 55 and 38, respectively.

After a thorough evaluation by an Ob/Gyn, the patient was found to have an enlarged uterus, a large fibroid, fluid in the endometrial cavity, and a growth in the lining of the uterus that was about an inch thick. An in-office biopsy revealed that it was indeed endometrial cancer.

One of the most common symptoms of endometrial cancer is abnormal vaginal bleeding, especially bleeding between periods or after menopause. Very long, heavy episodes of bleeding, abdominal or pelvic pain, and clear or white vaginal discharge after menopause are also regular symptoms. However, there can be other causes of any or all of these symptoms, so it is important to see your doctor if you experience any of them. As the case study above suggests, there can be a family or genetic predisposition for endometrial cancer if certain syndromes (like Lynch and Cowden) are present. These syndromes increase risk for a variety of cancers.

DIAGNOSING ENDOMETRIAL CANCER

As in the case history above, abnormal bleeding is the first symptom of more than 90 percent of cases of endometrial carcinomas, which luckily makes early diagnosis somewhat more likely. A physical or pelvic exam does not usually indicate much at all, although one's doctor might feel a slight enlargement of the uterus. An in-office biopsy of the lining of the uterus is often accurate (more than 90 percent sensitive) and detects many cases of endometrial carcinoma as well as precancerous lesions that are often precursors to the disease.

Pursuing the Warning Signs

With bleeding as the most common early warning sign, doctors must rule out all possible causes of bleeding, of which there can be several. Unusual bleeding in women over 35, as well as in a younger women who have a history of chronic missed periods are signs that should immediately prompt a doctor to test for endometrial cancer.

In some instances, women may have a negative biopsy but still have significant symptoms that suggest endometrial cancer. In these cases, doctors will often opt for a procedure called dilation and curettage (D&C), in which the lining of the uterus is scraped and the cells examined more closely. Another technique, called hysteroscopy, in which the uterus is evaluated with an endoscope (a camera on the end of a thin tube, inserted into the uterus through the vagina), may also be recommended.

A transvaginal ultrasound is another common technique, as it is sensitive and noninvasive. It can help evaluate postmenopausal patients with vaginal bleeding, and determine whether the bleeding is worrisome or not. Postmenopausal women who have a minor thickening of the endometrium, as visualized with ultrasound, generally have a low risk of endometrial disease. However, even in this group, if bleeding is recurrent or persistent, endometrial sampling must be carried out to rule out endometrial cancer or its precursor lesions.

After one is diagnosed with endometrial cancer, other lab tests may be done to look at blood counts and liver and kidney function. X-rays may also be taken to determine how advanced the disease is. Chest x-rays are often done to determine whether the cancer has spread to the lungs, since they are a common site of the metastasis of endometrial cancer.

Finally, a specific blood test may be done to measure levels of a glycoprotein called CA-125, since it can be elevated in the presence of endometrial cancer, as well as certain cervical and lung cancers. If it is elevated in endometrial cancer patients, it could mean that there is disease outside the uterus, and knowing this can help determine the best course of treatment.

Screening in High-Risk Women

Some doctors may choose to screen women who are at especially high risk. Women at risk include those who have a genetic predisposition, postmenopausal women who have been treated with estrogen replacement therapy without progesterone, premenopausal women with chronic missed periods that are untreated, and patients with estrogen-producing tumors. Taking the breast cancer medication Tamoxifen does not mean that a woman should automatically have endometrial "surveillance" with ultrasound or biopsy if they do not have other symptoms that could indicate endometrial cancer.

TREATMENT OPTIONS FOR ENDOMETRIAL CANCER

Endometrial cancer can be treated in a number of ways, including surgery, radiation therapy, hormone therapy, and chemotherapy. Depending on the type of cancer cell and the stage (I, II, III, or IV), these techniques can either be used alone or in combination with one another.

Surgery to Determine the Stage of Cancer

Patients who are healthy enough to do so typically have exploratory surgery so that one's doctor can determine how advanced the cancer is (that is, what stage it is), and begin to treat it. The doctor will also determine whether the patient is at low, intermediate, or high risk for cancer recurrence, based on various factors, like the stage of the cancer, the woman's age, and several variables having to do with the cancer cells themselves and whether or not they have spread. If the woman is determined to be at higher risk, chemotherapy and/or radiation may be required.

Presented by

Yevgeniya Ioffe & Israel Zighelboim

Yevgeniya Ioffe and Israel Zighelboim both work in the Division of Gynecologic Oncology at the Washington University School of Medicine and Siteman Cancer Center in St. Louis.

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