Everybody in this room is probably familiar with the risk factors of endometrial cancer, the number one risk factor would be obesity in the postmenopausal group, the reason for obesity being a risk factor is as androstene dione is peripherally converted to estrone in the adipose tissue, so the more adipose tissue you have, the potential for more estrone production you have, therefore more stimulation of your endometrial cavity. Nulliparity has always been a risk factor for endometrial cancer, it is unclear whether it’s because patient’s who do develop endometrial cancer may be anovulatory or they have no interruption of their hormonal stimulation of their endometrium. It has been shown that women who have been on oral contraceptives for at least 12 months at some point during their life, have a protective mechanism against endometrial cancer, so they feel that nulliparity is probably a lack of interruption of the constant estrogen stimulation of the endometrium.
If we look at late menopause again, this is a subjective symptom, sometimes you will have women who come in and say, well I have been bleeding and their 65 years old, well obviously they haven’t gotten with the program that they are having abnormal bleeding, they have gone through the change but they are having abnormal bleeding. Diabetes and hypertension is disease processes that are associated with the elderly and also associated with the obese. So it’s unclear whether diabetes and hypertension actually have a cause and effect relation with endometrial cancer, they tend to present with the patient package of an elderly patient who is overweight, who has adult onset diabetes and therefore has adult onset hypertension caused from her obesity. The number one risk factor for endometrial cancer is unopposed estrogen, and this is for the garden variety endometrial cancer, adenocarcinoma, it does not hold true for papillary or clear cell carcinomas, the run of the mill adenocarcinoma is associated with unopposed estrogen.
In recent years, there has been a lot of use with tamoxifen therapy in breast cancer prevention and in patient’s who have breast cancer to prevent the other breast from receiving tamoxifen in order to be protective against receiving another breast cancer in the opposite breast. There has been a lot of controversy in the literature saying that if you are on tamoxifen, your risk of developing endometrial cancer is seven times that of normal, and indeed that is true. However, of all the patient’s if you take 1000 patient’s who are on tamoxifen therapy for breast cancer prevention, out of the thousand, only two will develop endometrial cancer, therefore, 998 patient’s who are on tamoxifen will not get endometrial cancer. The type of endometrial cancer that patient’s get while they are on tamoxifen is exactly identical to what they get if they are not on tamoxifen. The present with postmenopausal bleeding and therefore, have an early warning sign that allows you to sample them. Patient’s who are on tamoxifen who develop endometrial cancer frequently will present with postmenopausal spotting and when you work them up, they will have a well differentiated tumor and a very early cancer that is very treatable with hysterectomy or radiation, whatever the case may be. Therefore, it is felt that the benefits of tamoxifen therapy far outweigh the risks and therefore, though there is a seven time increased risk of developing endometrial cancer on tamoxifen, the overall risk for patient’s on tamoxifen is actually quite low.