eMedicine Specialties > Obstetrics and Gynecology > Gynecologic Oncology

Endometrial Carcinoma

Author: William T Creasman, MD, J Marion Sims Professor, Department of Obstetrics and Gynecology, Medical University of South Carolina
Contributor Information and Disclosures

Updated: Aug 3, 2009

Introduction

Background

Corpus cancer is the most frequently occurring female genital cancer. Approximately 40,100 cases of corpus cancer were predicted to occur in the United States in 2008, making it the fourth most common cancer among women; of these women, approximately 7,400 will die from the disease.¹

In developed countries, adenocarcinoma of the endometrium is the most common gynecological cancer; however, in developing countries, it is much less common than carcinoma of the cervix. In the United States in the early part of the 20th century, cancer of the cervix killed more women than any other cancer, but in the ensuing decades, the incidence for that malignancy decreased precipitously. This decrease has been credited to the impact of screening with the Papanicolaou test (Pap smear). In less-developed countries, screening for cervical cancer is performed very infrequently, and therefore, cancer of the cervix is quite prevalent.

Frequency

United States

The latest Surveillance, Epidemiology, and End Results (SEER) data note a total age-adjusted 25.2 incidence of 24.4 cases per 100,000 people, with the incidence in white women being cases per 100,000 persons and the incidence in black women being 22.6 cases per 100,000 persons.¹

Mortality/Morbidity

• Approximately 40,100 cases of corpus cancer were predicted to occur in the United States in 2008, making it the fourth most common cancer among women; of these women, approximately 7,400 will die from the disease.¹

Race

• Mortality is higher in black women than in white women, with a mortality ratio of 7.3 deaths per 100,000 persons in black women and only 3.8 deaths per 100,000 persons in white women.

Sex

• Endometrial carcinoma occurs only in females.

Age

• Endometrial adenocarcinoma occurs during the reproductive and menopausal years.
• The median age of persons with this malignancy is early in the seventh decade of life, although most patients are aged 50-59 years. Approximately 5% of women younger than 40 years have adenocarcinoma, and 20-25% of women are diagnosed before menopause.

Clinical

History

• Because approximately 75% of women with endometrial cancer are postmenopausal, the most common symptom is postmenopausal bleeding.
  • Investigate all bleeding during menopause unless the patient is on cyclic replacement therapy with normally anticipated withdrawal bleeding. The duration or amount (staining vs gross) of bleeding does not make any difference.
  • The fact that only approximately 20% of postmenopausal bleeding is due to cancer is appreciated, but obviously, the diagnosis must be eliminated in these patients.
• Because 25% of endometrial cancers are in patients who are perimenopausal or premenopausal, symptoms suggestive of cancer may be more subtle. The idea that any type of bleeding during the perimenopausal period is probably due to menopause is a common misconception. This irregular bleeding is often ignored by the patient and even health care providers. Remember that the normal bleeding pattern during this time should become lighter and lighter and further and further apart. Heavy frequent menstrual periods or intermenstrual bleeding must be evaluated.

Physical

• Because bleeding usually occurs from the endometrium, pelvic examination findings may be entirely normal, with no gross evidence of disease on the cervix and with a normal-sized uterus.
  • Bleeding leads to an evaluation of the endometrium. In the vast majority of cases, no gross evidence of disease is noted.
  • The uterus may be of normal size upon pelvic examination.
  • Cancer can be present upon cervical evaluation and, less frequently, in the upper vagina or periurethrally. In current practice, occult cervical involvement is very unusual, as is clinically evident metastasis, such as in the vagina.

Causes

• Endogenous factors
  • Obesity increases the risk for developing endometrial cancer, and some data suggest that a 2- to 3-fold increase in risk occurs if an individual is more than 50 lb heavier than the ideal weight for that person.
  • Nulliparity also increases risk 2- to 3-fold compared with parity.
  • An individual who has had a late menopause (aged >52 y) also appears to have an increased risk.
• Unopposed estrogen
  • Unopposed estrogen, either as replacement therapy or endogenously produced (eg, granulosa cell tumor, polycystic ovarian disease), increases the risk of endometrial cancer several times.
  • Obesity is known to increase endogenous estrogen because the presence of fat appears to be responsible for the conversion of androstenedione to estrogen compounds at a much higher rate than if fat is not present.
  • Anovulation, which may be secondary to unopposed estrogen, also appears to contribute to this situation.
• Tamoxifen
  • The most widely used anticancer drug is tamoxifen, and this drug has been suggested by some studies to cause an increased incidence of adenocarcinoma of the endometrium. These data were derived from retrospective analyses in which adenocarcinoma of the endometrium was not an end point in multiple prospective randomized studies evaluating the role of tamoxifen in patients with breast cancer.²
  • A case control study using the SEER database indicates that when confounding factors have been corrected, the risk of endometrial cancer does not appear to be increased in patients taking tamoxifen.³ This study is very reassuring because the potential for an increased number of women taking tamoxifen is becoming apparent, particularly as the prophylactic role of tamoxifen has been recommended for high-risk women.
• Combination oral contraceptives
  • In contrast to tamoxifen, increasing data indicate that the use of combination oral contraceptives (OCs) decreases the risk of developing endometrial cancer.
  • Several studies have noted that women who use OCs at some time have a 0.5 relative risk of developing endometrial cancer compared with women who have never used OCs.
  • This protection occurs in women who have used OCs for at least 12 months, and the protection continues for at least 10 years after OC use. Protection is most notable for nulliparous women.
• Cigarette smoking
  • Smoking apparently decreases the risk of developing endometrial cancer.
  • The effects of smoking are related to body weight. Heavier women who smoke have the greatest reduction in risk.
  • Women who smoke are known to undergo menopause 1-2 years earlier than women who do not smoke.
  • Although smoking apparently reduces the risk of developing early stages of endometrial cancer, this advantage is strongly outweighed by the increased risk of lung cancer and other major health problems associated with smoking.
• Associated medical conditions
  • Some associated medical conditions have been found to increase the incidence of endometrial cancer.
  • Breast, colon, and ovarian cancers are frequently observed in women with endometrial cancer.
  • Data suggest that women who have had breast cancer have a 2- to 3-fold increased risk of subsequently developing endometrial cancer.
  • Women who have hereditary nonpolyposis colon cancer (HNPCC) appear to have a markedly increased risk for developing endometrial cancer.
    • Women with HNPCC account for only 2-10% of all female cases of colon cancer, but approximately 5% of all endometrial cancers occur in women with this risk factor. These women have a 22-50% lifetime risk of developing endometrial cancer, and the disease tends to occur at a younger age (approximately 15 y earlier). The greatest risk of developing endometrial cancer in women with HNPCC occurs from age 40-60 years, at which time the absolute risk is greater than 1% per y.
    • Currently, no data indicate that annual screening of women with HNPCC will detect endometrial cancer at a sufficiently early stage to improve survival compared with those whose diagnosis is made when symptoms appear. Nevertheless, because of the high risk of endometrial cancer in these individuals and because of the potential life-threatening nature of this disease, HNPCC patients should be so informed and screening is certainly suggested. According to American Cancer Society guidelines, women with HNPCC should be offered screening with an endometrial biopsy by age 35 years.
• Family history: Individuals with a family history of endometrial cancer appear to be at increased risk.
• Phenotype characteristics
  • At one time, a classic phenotypic characteristic was thought to exist for a woman who would develop endometrial cancer. This phenotype included patients who were obese, nulliparous, and anovulatory in many instances. More recently, the existence of 2 pathogenic types of endometrial cancer was appreciated.
  • The first type occurs in women who fall into the classic category. These women are obese and have hyperlipidemia, signs of hyperestrogenism, uterine bleeding, infertility, and late onset of menopause. They may have hyperplasia of the ovary and endometrium. These patients tend to be white, obese, nulliparous, and have well-differentiated superficially invasive cancers that are sensitive to progesterone. They have a very favorable prognosis, and extrauterine disease is unusual in this group of patients. Fortunately, most women with endometrial cancer are in this category.
  • The second type occurs in women who have none of the disease states present in the classic presentation. These individuals tend to have poorly differentiated tumors, deep myometrial invasion, a high degree of metastasis to the lymph nodes and other sites, decreased sensitivity to progestins, and a poor prognosis. These patients tend to be thin, multiparous, and African American.

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