Endometrial cancer is the fourth-most-common cancer diagnosed in women in the United States, following breast, lung, and colorectal cancer in frequency. It accounts for 6% of all cancers in women, with an estimated 54,870 new cases in 2015. It is the most common gynecologic malignancy in the United States. One in 40 women will develop endometrial cancer in their lifetime, and the American Cancer Society estimated there would be 10,470 deaths from this disease in 2016. Endometrial cancer is typically a disease seen in perimenopausal and postmenopausal women. The likelihood of developing an endometrial cancer is rare before the age of 40 (<5%), and the risk increases thereafter, with median age at diagnosis of 63. Caucasian women are twice as likely to be affected.
Endometrial cancers can be divided into 2 categories: type 1 and type 2.1 Type 1 endometrial cancer includes endometrioid adenocarcinoma grades 1 and 2 and is more frequent. It is recognized to be estrogen related and hormonally dependent. It typically arises in patients with a hyperestrogenic state. Excess estrogen exposure can result from a variation of the normal reproductive physiology, as is seen in anovulatory cycles, polycystic ovary disease, prolonged perimenopause or late menopause with anovulatory bleeding pattern, or obesity. Alternatively, estrogen excess can be the result of iatrogenic administration or estrogen-secreting ovarian tumors. The risk of endometrial neoplasia is greater for nulliparous women. It is hypothesized that this process may be related to prolonged periods of infertility, correlating with anovulatory menstrual cycles, excessive serum levels of androstenedione, and lack of monthly sloughing of the endometrial lining. These tumors are typically estrogen and progesterone receptor (PR) positive and have a high sensitivity to progestins. Patients have a favorable prognosis, and 5-year survival of approximately 85%. Obesity in particular increases the risk of type 1 endometrial cancers.
Type 2 endometrial cancers represent the opposite end of the spectrum. These tumors are typically more aggressive. They do not need a hyperestrogenic environment for development. These cancers are high grade, display high-risk cell types, and are not hormonally driven. Examples include grade 3 endometrioid adenocarcinomas and serous, clear cell, and undifferentiated cancers. Type 2 tumors have a higher incidence of deep myometrial invasion and, in comparison to type 1, a higher metastatic potential. Because these tumors are frequently estrogen receptor negative, they have low response rates to progestins. They have a relatively poor prognosis, with a 5-year survival of 58%. Patients with type 2 cancers are typically thinner and older and have no apparent stigmata or history to suggest a hyperestrogenic state. Type 2 tumors are not associated with obesity.
EPIDEMIOLOGIC EVIDENCE SUPPORTING ROLE OF OBESITY IN ENDOMETRIAL CANCER
Over 60% of adults in the United States have a body mass index (BMI) over 25, making them either overweight or obese. In a UK study, data from the Clinical Practice Research Datalink (CPRD) was utilized to examine associations between BMI and risk of individual cancers, adjusting for potential confounders. Each 5-kg/m2 increase in BMI was linearly associated ...