New Treatments for Endometrial Cancer. Part 2
From the standpoint of the molecular biology of the disease, frankly this disease is not well characterized. What is not on this slide here but you should remember is this is a hormonally influenced disease; estrogen and progesterone receptors are present in endometrial tissue and also in tissue associated with endometrial carcinoma. We’ll tell you a little more in a few minutes about the frequency of that and what impact that has on outcome with hormonal treatments. But remember that that is a part of the molecular biology of endometrial carcinoma. Endometrial carcinoma is also a part of the Lynch type II syndrome, as we pointed out in the talk on ovarian carcinoma. That syndrome has an increased frequency of breast, colorectal, endometrial and ovarian carcinomas. An over-expression of HER2/neu, we really don’t know what the facts are here. The frequency of HER2/neu over-expression ranges from 10% to 85%, depending upon what article in the literature you want to pull and look at. All of these are relatively small series so we don’t know the true frequencies yet. As is the case in both breast and ovarian carcinomas, HER2 over-expression is a poor prognostic factor. We have no idea as yet what role the monoclonal antibody might play in this disease or what over-expression of HER2/neu will tell us about the source of treatments we ought to be applying to these patients.
The disease presents in the peri and postmenopausal age groups, beginning at about age 40 and rising in incidence as you proceed into the postmenopausal years. As we’ve mentioned from the risk factor slide, associated factors are obesity, hypertension and diabetes. As a result of this, this has come to be known as a fragile patient population that does not tolerate aggressive treatment approaches well. Frankly, within the gynecologic oncology group we’ve not found that that’s the case. We started our trials of chemotherapy in these patients 25 years ago with very modest doses. The doses we use now are pretty much the doses we would use in breast cancer, ovarian cancer, and other diseases where those same drugs are appropriate. So despite the fact that this patient population does have comorbid conditions, the patients do appear to be able to tolerate reasonably aggressive approaches.
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The principal presenting manifestation of the disease is bleeding, and this accounts for why we are able to diagnose this disease process at an early stage in the vast majority of patients. If your patient presents with abnormal bleeding of any kind, particularly in the peri or postmenopausal years, that patient should be considered to have endometrial carcinoma until proven otherwise. That is an indication for sampling of the endometrium by your friendly gynecologist. The key prognostic factor for these patients is the extent of disease at the time of diagnosis or the stage. The staging system of endometrial carcinoma currently is a surgical/pathological staging system. This is an abbreviated version; stage I disease is disease confined to the corpus, stage II disease is disease that has extended to involve the cervix, stage III is regional spread to involve the adnexa, the serosa, positive peritoneal cytology, involvement of the vagina or the perimetrium. Stage IV disease is either bladder or rectal mucosal involvement, which is stage IVa, or spread outside the pelvis, which is stage IVb. Stages I, II and III are subdivided according to grade as well, so that the grade needs to be specified in order to get a good handle on what prognosis you might be dealing with. You’ll note that survival figures out here show that 90% of the patients who present with stage I disease will be cured, 60% with stage II, 40% for stage III and less than 10% for stage IV. The actual figures show that 75% of these patients are diagnosed as stage I, another 13% as stage II. So that’s 88% of all patients will have either stage I or stage II disease, which is amenable to surgical and radiotherapy approaches. Stage III disease accounts for 9% of all cases, and stage IV disease, 3% of all cases. So this is a disease process that’s diagnosed usually at an early stage of development because of the presenting manifestation of bleeding.