Chapter 1: Epidemiology of Gynecologic Cancers, Clinical Trials, and Statistical Considerations

EPIDEMIOLOGY OF GYNECOLOGIC CANCERS

The burden of cancer on our population is expected to rise sharply over the next 20 years. This is the result of the aging and growth of the world's population, alongside an increasing adoption of cancer-causing behaviors, particularly smoking and increasing obesity. Overall, cancer incidence is expected to increase by 45% between 2010 and 2030, with the greatest increase borne by older adults and minorities. By 2030, approximately 70% of all cancers will be diagnosed in older adults, and 28% of all cancers will be diagnosed in minorities.¹ Resources will be required to effect and optimize cancer prevention, screening, and early detection. Meaningful improvements in cancer therapy and/or prevention strategies will be required to prevent a dramatic increase in the number of cancer deaths over the next 20 years.

Uterine Corpus Cancer

Endometrial cancer is the most common gynecologic cancer and the fourth most common cancer of women in the United States; 43,470 new cases diagnosed are predicted for 2010, with 7950 deaths.² A 50-year old woman in the United States has a 1.3% probability of being diagnosed with endometrial cancer before age 70 years.

Eighty-seven percent of all endometrial cancers are of endometrioid histology. The most common nonendometrioid histology is papillary serous (10%), followed by clear cell (2%-4%), mucinous (0.6%-5%), and squamous cell (0.1%-0.5%). Some nonendometrioid endometrial carcinomas behave more aggressively than the endometrioid cancers such that even women with clinical stage I disease often have extrauterine metastasis at the time of surgical evaluation.³ Features of type 1 (endometrioid) carcinoma include increased exposure to estrogen (nulliparity, early menarche, chronic anovulation, and unopposed exogenous estrogen), obesity, and responsiveness to progesterone therapy. Patients more often are white, younger in age, present with a low-grade cancer, and have a better prognosis. The precursor to this malignancy is endometrial hyperplasia. Type 1 endometrial cancers often have a phosphatase and tensin homolog (PTEN) mutation and a higher incidence of microsatellite instability. In contrast, type 2 endometrial cancers are unrelated to estrogen exposure and occur in older, thinner women. The most common forms of type 2 endometrial cancer include uterine papillary serous carcinoma and clear cell carcinoma. Uterine papillary serous cancers are aggressive, with an increased incidence of p53 and HER-2/neu overexpression.

Risk factors for endometrial cancer include diabetes, obesity, hypertension, nulliparity, polycystic ovarian syndrome, unopposed estrogen therapy, tamoxifen usage, infertility or failure to ovulate, and late menopause.⁴ A number of studies have reported a positive association between diabetes and incidence of mortality from endometrial cancer.⁵ Diabetes mellitus (both types 1 and 2) has been associated with up to a 2-fold increased risk of endometrial cancer.

Adult overweight/obesity is one of the strongest risk factors for endometrial cancer. In affluent societies, adult obesity accounts for approximately 40% of the endometrial cancer incidence.⁶ In postmenopausal women, adiposity is ...