Chapter 6: Endometrial Hyperplasia and Cancer

INTRODUCTION

Endometrial cancer is the most common malignancy of the female genital tract in the United States. Women have an overall lifetime risk of 2.5% of developing endometrial cancer. Fortunately, the majority of endometrial present at early stages with postmenopausal bleeding. Although obesity and estrogen excess remain the strongest risk factors for this disease, Lynch syndrome comprises the majority of inherited endometrial cancer cases; affected women have a 40% to 60% predicted lifetime risk of developing endometrial cancer.

For early-stage disease, standard management includes total abdominal hysterectomy, bilateral salpingo-oophorectomy, and staging. Management for women with advanced-stage disease primarily involves surgical resection and chemotherapy. Radiation therapy may be used for local control or in treating patients with positive lymph nodes, and hormonal therapies have been shown to be effective in a subset of patients. Several novel molecular-targeted therapies have been developed and evaluated for the treatment of endometrial carcinoma. The principal benefit to these drugs, at this time, has been to prolong stable disease.

EPIDEMIOLOGY

Key Points

1. Endometrioid endometrial carcinomas account for approximately 80% of cases and typically occur in perimenopausal or postmenopausal women, are often of lower histologic grade, are often confined to the uterus and have a more favorable prognosis.

2. Risk factors associated with the development of endometrioid endometrial cancer include obesity, tamoxifen use, chronic anovulation, exogenous estrogen administration, nulliparity, early menarche, and/or late menopause.

3. Type 1 and 2 endometrial carcinomas exhibit distinct molecular alterations. The most common molecular alteration associated with type 1 tumors is loss of PTEN, whereas in type 2 tumors, it is p53 mutations.

Incidence

Endometrial cancer is the most common gynecologic malignancy in the United States. An estimated 43,470 women will be diagnosed with uterine cancer in 2010, and it is estimated that 7950 of these women will die of the disease.¹ Endometrial adenocarcinoma typically affects women in their perimenopausal or postmenopausal years and is most frequently diagnosed in women between the ages of 50 and 65 years. However, approximately 5% of cases are diagnosed in women before the age of 40 years, and approximately 10% to 15% of women are diagnosed before the age of 50 years.² Women have an overall lifetime risk of 2.53% (1 in 40) of developing endometrial cancer.¹ Approximately 90% of uterine tumors arise within the endometrium and are categorized as endometrial carcinomas. Of the endometrial carcinomas, 80% are endometrioid adenocarcinomas, and 15% to 20% are of more rare subtypes: papillary serous, clear cell, mucinous, or mixed carcinomas. These uncommon subtypes are associated with a poorer prognosis and greater risk of extra-uterine metastases when compared with endometrioid adenocarcinomas.

Risk Factors

Multiple well-defined risk factors are associated with endometrial cancer and vary depending on the histologic subtype (Table 6-1). Type 1 endometrial cancer is ...