Clinical Pearls & Morning Reports
Published November 18, 2020
Unlike most other cancers in the United States, endometrial cancer is rising in both incidence and associated mortality. Read the NEJM Review Article here.
Q: Name an important risk factor for endometrial cancer.
A: Obesity is one of the most important risk factors for this disease, and as rates of obesity have risen, rates of endometrial cancer have also increased. In the United States, 57% of all endometrial cancers are attributable to obesity. As compared with all other cancers, endometrial cancer has the strongest association with obesity. Endometrial cancer is increasingly being diagnosed in young obese women. Although the average age at diagnosis is 63 years, data from the Surveillance, Epidemiology, and End Results program from 1990 to the present show a sustained rise in cases among women under the age of 50 years.
Q: What is the lifetime risk of endometrial cancer in women with the Lynch syndrome?
A: Women with the Lynch syndrome, diagnosed on the basis of a germline mutation in an MLH1 or MSH2 mismatch-repair gene, have a lifetime risk of endometrial cancer of 40 to 60%, with a median age at onset of 48 years. Identification of the Lynch syndrome in patients with endometrial cancer has become increasingly important, since immune checkpoint blockade has been approved for the treatment of advanced disease with high microsatellite instability. Another factor favoring identification of patients with the Lynch syndrome is that they are at increased risk for colon cancer.
A: Endometrial carcinoma arises from the lining of the uterus and can broadly be divided into two types: endometrioid, affecting approximately 80% of patients, and nonendometrioid, affecting approximately 20% of patients. In both premenopausal and postmenopausal patients, endometrioid tumors typically arise from endometrial complex atypical hyperplasia with epithelial atypia. Relative estrogen excess, such as that associated with obesity, the use of unopposed estrogen for hormone-replacement therapy, and estrogen-producing tumors (e.g., ovarian granulosa-cell tumors), predispose women to the development of endometrioid-type endometrial carcinoma. Nonendometrioid tumors, in contrast, have a hormone-independent pathogenesis and no known precursor lesions. Nonendometrioid endometrial carcinomas include endometrial serous carcinoma, clear-cell carcinoma, and carcinosarcoma. Endometrial serous carcinoma is the most common of the nonendometrioid tumors and typically has a poor prognosis. Carcinosarcomas typically have worse outcomes than endometrioid, clear-cell, and serous carcinomas.
A: The rates of endometrial cancer and associated mortality are rising among women of all backgrounds, but during the past decade, the rates have risen most sharply among Black women. Because Black women have higher rates of hysterectomy than White women, hysterectomy-adjusted rates of endometrial cancer highlight the disproportionate rise in incidence. Of particular concern is the higher rate of increase among Black women of tumors with aggressive, nonendometrioid histologic features. The cause of this increase in unclear. Although older, thin Black women often present with uterine serous cancer, a population-based analysis showed that Black women under the age of 50 years, as compared with White women in the same age group, were more likely to present with higher-grade, nonendometrioid tumors, as well as later-stage tumors. After adjustment for stage and histologic features, young Black women with early-stage tumors had a 24% higher likelihood of dying, as compared with their White counterparts.