General Information About Endometrial Cancer
Cancer of the endometrium is the most common gynecologic malignancy in the United States and accounts for 6% of all cancers in women. The majority of cases are diagnosed at an early stage and are amenable to treatment with surgery alone. However, patients with pathologic features predictive of a high rate of relapse and patients with extrauterine spread at diagnosis have a high rate of relapse despite adjuvant therapy.
Incidence and Mortality
Estimated new cases and deaths from cancer of the uterine corpus, which includes the endometrium, in the United States in 2017:
- New cases: 61,380.
- Deaths: 10,920.
Endometrial cancer is usually diagnosed and treated at an early stage. Cardiovascular disease is the most common cause of death in patients with endometrial cancer because of the related metabolic risk factors.
The endometrium is the inner lining of the uterus and has both functional and basal layers. The functional layer is hormonally sensitive and is shed in a cyclical pattern during menstruation in reproductive-age women. Both estrogen and progesterone are necessary to maintain a normal endometrial lining. However, factors that lead to an excess of estrogen, including obesity and anovulation, lead to an increase in the deposition of the endometrial lining. These changes may lead to endometrial hyperplasia, and, in some cases, endometrial cancer. Whatever the cause, a thickened lining will lead to sloughing of the endometrial tissue through the endometrial canal and into the vagina. As a result, heavy menstrual bleeding or bleeding after menopause are often the initial signs of endometrial cancer. This symptom tends to happen early in the disease course, allowing for identification of the disease at an early stage for most women.
Risk factors for endometrial cancer include the following:
- Endometrial hyperplasia.
- Hormone therapy.[3,4]
- Tamoxifen therapy.[5,6]
- Reproductive factors (nulliparity, early menarche/late menopause, or polycystic ovarian syndrome).
- Family history/genetic predisposition.[7,8]
Prolonged, unopposed estrogen exposure has been associated with an increased risk of endometrial cancer.[3,4] However, combined estrogen and progesterone therapy prevents the increase in risk of endometrial cancer associated with unopposed estrogen use.[10,11]
Tamoxifen, which is used for both the treatment and prevention of breast cancer (NSABP-B-14), is associated with an increased risk of endometrial cancer related to the estrogenic effect of tamoxifen on the endometrium.[5,6] It is important that patients who are receiving tamoxifen and experiencing abnormal uterine bleeding have follow-up examinations and biopsy of the endometrial lining. The U.S. Food and Drug Administration released a black box warning that includes data about the increase in uterine malignancies associated with tamoxifen use. (Refer to the Lynch Syndrome (LS) section in the PDQ summary on Genetics of Breast and Gynecologic Cancers for more information about risk factors for LS-associated endometrial cancer.)
Irregular vaginal bleeding is the most common presenting sign of endometrial cancer. It generally occurs early in the disease process, and is the reason why most patients are diagnosed with highly curable stage I endometrial cancer.
The following procedures may be used to detect endometrial cancer:
- Transvaginal ultrasound.
- Endometrial biopsy.
- Pelvic exam.
- Dilatation and curettage (D&C).
To definitively diagnose endometrial cancer, a procedure that directly samples the endometrial tissue is necessary.
The Pap smear is not a reliable screening procedure for the detection of endometrial cancer, even though a retrospective study found a strong correlation between positive cervical cytology and high-risk endometrial disease (i.e., high-grade tumor and deep myometrial invasion). A prospective study found a statistically significant association between malignant cytology and increased risk of nodal disease.
Prognostic factors for endometrial cancer include the following:
- Tumor stage and grade (including extrauterine nodal spread).
- Hormone receptor status.
Tumor stage and grade (including extrauterine nodal spread)
The following table highlights the risk of nodal metastasis based on findings at the time of staging surgery:
Table 1. Risk of Nodal Metastasis in Clinical Stage I Endometrial Cancer
|Prognostic Group||Patient Characteristics||Risk of Nodal Involvement|
|A||Grade 1 tumors involving only endometrium||<5%|
|No evidence of intraperitoneal spread|
|B||Grade 2–3 tumors||5%–9% pelvic nodes|
|Invasion of <50% of myometrium|
|No intraperitoneal spread||4% periaortic nodes|
|C||Deep muscle invasion||20%–60% pelvic nodes|
|High-grade tumors||10%–30% periaortic nodes|
A Gynecologic Oncology Group study related surgical-pathologic parameters and postoperative treatment to recurrence-free interval and recurrence site. Grade 3 histology and deep myometrial invasion in patients without extrauterine spread were the greatest determinants of recurrence. In this study, the frequency of recurrence was greatly increased with the following:[15,16]
- Positive pelvic nodes.
- Adnexal metastasis.
- Positive peritoneal cytology.
- Capillary space involvement.
- Involvement of the isthmus or cervix.
- Positive periaortic nodes (includes all grades and depth of invasion). Of the cases with aortic node metastases, 98% were in patients with positive pelvic nodes, intra-abdominal metastases, or tumor invasion of the outer 33% of the myometrium.
When the only evidence of extrauterine spread is positive peritoneal cytology, the influence on outcome is unclear. The value of therapy directed at this cytologic finding is not well founded,[17-22] and some data are contradictory. Although the collection of cytology specimens is still suggested, a positive result does not upstage the cancer. Other extrauterine disease must be present before additional postoperative therapy is considered.
Involvement of the capillary-lymphatic space on histopathologic examination correlates with extrauterine and nodal spread of tumor.
Hormone receptor status
Progesterone and estrogen receptors, assessed either by biochemical or immunohistochemical methods, are included, when possible, in the evaluation of patients with stage I and stage II cancer.[25-27]
One report found progesterone receptor levels to be the single most important prognostic indicator of 3-year survival in clinical stages I and II disease. Patients with progesterone receptor levels above 100 had a 3-year disease-free survival (DFS) of 93%, compared with a 36% DFS for a level below 100. After adjusting for progesterone receptor levels, only cervical involvement and peritoneal cytology were significant prognostic variables.
Other reports confirm the importance of hormone receptor status as an independent prognostic factor. Additionally, immunohistochemical staining of paraffin-embedded tissue for both estrogen and progesterone receptors has been shown to correlate with Féderation Internationale de Gynécologie et d’Obstétrique (FIGO) grade and survival.[25-27]
Other prognostic factors
Other factors predictive of poor prognosis include the following:[27,30,31]
- A high S-phase fraction.
- Absence of PTEN.
- PIK3CA mutation status.
- p53 mutation status.
- Her-2/neu overexpression.
- Oncogene expression (e.g., overexpression of the Her-2/neu oncogene has been associated with a poor overall prognosis).
A general review of prognostic factors has been published.
- American Cancer Society: Cancer Facts and Figures 2017. Atlanta, Ga: American Cancer Society, 2017. Available onlineExit Disclaimer. Last accessed October 13, 2017.
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- Morrow CP, Bundy BN, Kurman RJ, et al.: Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study. Gynecol Oncol 40 (1): 55-65, 1991. [PUBMED Abstract]
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- Hetzel DJ, Wilson TO, Keeney GL, et al.: HER-2/neu expression: a major prognostic factor in endometrial cancer. Gynecol Oncol 47 (2): 179-85, 1992. [PUBMED Abstract]
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