New Treatments for Endometrial Cancer
From the data in adjuvant studies of tamoxifen in breast cancer and also breast cancer prevention trial data, what we come up with is this. That the hazard rate for endometrial carcinoma rises, from about 0.2 to 1.6 cases per thousand. Now in the actual NSABP prevention trial it was a rise from 0.9 to 2.0. If you look at the rest of the literature, the rise is roughly from 0.2 to 1.6. That’s a relative risk of 7.5, a dramatic increase in the likelihood of developing endometrial carcinoma, although the incidence still remains low. Two or fewer cases per thousand. The reduction in breast cancer relapse in patients who were taking tamoxifen for adjuvant therapy was in 227.8 cases per thousand, down to 123.5 cases per thousand. Now the reduction in second primary breast cancers fell from 40.5 to 23.5 cases per thousand. So the overall impact, taking the bad and the good together, is that there is a 38% reduction in the five year cumulative hazard rate if patients take tamoxifen, for either breast cancer prevention or prevention of recurrence, than if they don’t take tamoxifen. So the weight of evidence still favors the use of tamoxifen even though there is an increased risk for the development of endometrial carcinoma.
The current position taken by the American College of Obstetrics and Gynecology does not suggest periodic endometrial sampling, but simply close follow-up and asking about symptomatology, such as abnormal vaginal bleeding or discharge. If that appears, then that would be a reason for a gynecologic evaluation, including sampling of the endometrium and it would be a red flag for the potential presence of endometrial carcinoma.
Endometrial hyperplasia is a lesion that is associated with the development of endometrial cancer. This is classified as simple, complex or atypical. And atypical is divided into simple atypical hyperplasia and complex atypical hyperplasia. The risk of progression to malignancy for each of these is 1% of patients with simple hyperplasia will go on to develop endometrial carcinoma. Complex hyperplasia, 3% will go on to develop endometrial carcinoma. With simple atypical hyperplasia, 8% and with complex atypical hyperplasia, 20%. The standard of care, particularly for the complex atypical hyperplasia is hysterectomy. There have been some suggestions that an alternative approach to this would be to give progestins. That actually is an approach that is under evaluation now in the gynecologic oncology group in a formal clinical trial. But the standard of care remains hysterectomy for atypical endometrial hyperplasia, particularly complex atypical endometrial hyperplasia.