Treatments for Endometrial Cancer
There are a number of risk factors that have been reported. This is an attempt to summarize all of these risk factors, for those of you who are taking the Board. Obesity is clearly associated with endometrial carcinoma. We think because obesity leads to differences in the way hormonal agents are handled in the body. If the patient is over 30 pounds overweight there is a threefold increase in the risk of endometrial carcinoma. If they are overweight by more than 50 pounds that increases to a tenfold increase in risk. Nulliparity is increased with an increased risk twofold, late menopause 2.4-fold increase – by the way, this late menopause is after age 55 – a bloody menopause, that is, abnormal bleeding at the time of menopause a fourfold increase in risk. Diabetes is associated with endometrial carcinoma. A lot of the patients are diabetic. Diabetics have a 2.8-fold increase in risk. Hypertension, 1.5-fold increased risk. The two big ones though are: unopposed estrogen stimulation of the endometrium is associated with a 9.5-fold increase in risk, and if the patient has complex atypical hyperplasia, as we will discuss in more detail in a few moments, this lesion here is associated with a dramatic increase in the likelihood of developing full-blown endometrial carcinoma, twenty-nine-fold increase in risk. Now you know out of all this list, the three biggest increases in risk are associated with marked obesity, unopposed estrogen stimulation and documented presence of complex atypical hyperplasia. Those are your three principle risk factors.
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Now etiologically, unopposed estrogen stimulation and tamoxifen have both been associated. Tamoxifen is probably associated because it does have weak estrogenic effects. We’ve already mentioned there is clearly an increased risk of endometrial carcinoma with prolonged tamoxifen therapy, and we’ll look at this problem in a few minutes because you will probably see this on the Boards. The greatest cumulative risk for endometrial carcinoma occurs at about the five year point of tamoxifen use, which happens to be the period of duration of therapy for no negative breast cancer and was used in the breast cancer prevention trial. There was a publication from Yale about seven or eight years ago that suggested that the endometrial carcinomas that patients developed as a result of tamoxifen stimulation tended to be more advanced stage and higher grade lesions than normal. That is not the case. The rest of the literature suggests that in fact what we see is the same stage distribution that we see in sporadic endometrial carcinoma with no differences in stage, grade or prognosis of the endometrial carcinoma that develops. In other words, the risk of your patient dying of endometrial cancer as a result of tamoxifen is going to be very very low.