In terms of molecular biology, we don’t have a lot of hard information on ovarian carcinoma. Things that you probably ought to take note of are that any mutations of P53 seen in ovarian carcinomas are probably a late change and have nothing to do with etiology. Number two, ras mutations are associated with borderline tumors of the ovary, which we will comment on in just a few moments. And number three, the frequency with which HER2/neu is over expressed is probably considerably lower in ovarian carcinoma than is the case in breast cancer. The GOG currently is running a trial looking at Herceptin ovarian carcinoma. We’ve had to screen 550 patients just to find 25 who are either 2+ or 3+ or HER2 and therefore candidates for clinical trial. And out of those 25 there has been only one responder to Herceptin. So it would appear that HER2/neu is going to be much less of an important factor in ovarian carcinoma than appears to be the case in breast cancer. As yet we have no unifying model relative to molecular factors.

In terms of environmental factors; there are a number of proposed risk factors, none of which have been confirmed. High dietary intake of meat and animal fat has been associated. A high ratio of lactose consumption to red blood cell galactose 1-phosphate uridyltransferase has been postulated. Again not proven. Consumption of coffee, tobacco and alcohol have all been studied. There are some positive reports in the literature but there are a lot of others that deny an association. Then finally, there have been associations reported with industrial exposure, radiation and talcum powder used at surgery. Also mumps. But none of these are confirmed. There are no clear environmental factors that have been directly related to the disease process as yet.

In the area of prevention, there have been four methods proposed; use of oral contraceptives, the use of fenretinide, tubal ligation and prophylactic oophorectomy. And we’ll dispense with these middle two very quickly. There is an ongoing trial in Europe looking at fenretinide and there will soon be a randomized trial in the United States looking at this as a means of preventing ovarian carcinoma, but as yet we have no proof of efficacy. Tubal ligation is associated with a clear reduction in the risk of ovarian carcinoma, and this gets back to what we talked about earlier. That it is reducing the exposure of the peritoneal cavity to external agents. At least we think that’s the case. There is a clear reduction in risk with tubal ligation.

The other two topics have been looked at a good bit more in the literature. First of all, oral contraceptives; it’s clear that a five-year, five consecutive years of use, of oral contraceptives will reduce the risk of nulliparous women to that of multiparous women who don’t use birth control pills. So the use of birth control pills for five or more consecutive years is associated with a risk reduction. The use of birth control pills for ten or more years by patients with a positive family history will reduce their risk to below that of patients who don’t use oral contraceptives and who have negative family histories. The hazard ratio for women with positive family histories who use birth control pills as compared to those who do not is 0.5. A 50% reduction at 10 years, in the risk of developing ovarian carcinoma. Now there are no hard and fast recommendations on whether or not to use oral contraceptives. More importantly, we do not have good studies on the effects of oral contraceptives in those patients who have hereditary syndromes. So we do not know what the impact will be in that specific subset. So any decision regarding the use of oral contraceptives would have to be made in consultation with the patient and would also have to take into account other risks, such as the 1.46 hazard ratio associated with breast carcinoma in the ten or more years consecutive use of oral contraceptives.