OCRP 2012 Investigator Vignette

Title: Assessing and Reducing Familial Ovarian Cancer Risk

Investigator: Mary B. Daly, MD, PhD; Fox Chase Cancer Center

In the early 90s when we were just learning about familial causes of cancer and beginning to understand that there could be a genetic cause to some of these cancers; unlike breast cancer where there was a lot of information available to the public, there was almost nothing back then for these women who were at increased risk because they had a relative with ovarian cancer. And they were very hungry for information, education; what they could do to affect their risks, what would their daughters' risks be. And in 1991 we established a formal family risk assessment program for women with ovarian cancer, either themselves or a loved one's ovarian cancer.

Grant funding is pretty much reserved for studying a scientific hypothesis. And the DoD offered us an opportunity to get grant funding to set up the infrastructure for this family program. So it was one of the few funding opportunities to get such a program started and off the ground. The goal of that grant was to organize a family risk assessment program around risk for ovarian cancer. It enabled us to recruit many family members from these families, the men as well as the women, so that we could learn about how these cancers filter through families. And that was when we learned, for instance that ovarian cancer genes can be passed on through the paternal side of the family as well as the maternal side.

So we collected vast amounts of information. By that I mean family histories, medical histories, histories of exposure to perhaps carcinogens in the environment, hormone and reproductive histories. And we collected a blood sample from everyone who joined the registry. We have a bio-bank, and still do, of everyone who joined the registry so that we could begin to make these resources available to investigators both here and at other institutions to do research on the causes and prevention of ovarian cancer.

The importance of having a program like this that was funded by the DoD is that we can share these resources and leverage it for additional studies, additional collaborations, and partnering with other institutions and scientists. This is particularly important for ovarian cancer because it's rare and no one institution can collect enough of these families to have meaningful statistics.

Over the past few years, by sharing information with other institutions, we've been involved with several large consortia of investigators not just in the United States but across the world. And a lot of interesting information has evolved from these collaborations. One important one I think that's immediately clinically relevant is the discovery of what is the impact of prophylactic oophorectomy on subsequent ovarian cancer risk. So we together with several other institutions studied several thousand women who were BRCA carriers who underwent prophylactic surgery and compared them to women of the same risk who chose not to have surgery and have now established without any doubt that there's about a 95% reduction in risk of developing ovarian cancer from the surgery.

It's also allowed us to see what the impact on breast cancer. By removing the ovaries we reduce the risk of breast cancer presumably by eliminating the hormonal contribution to breast cancer. And we've also learned some of the negative side effects of removing the ovaries from young women; the long-term cardiovascular and bone mineral density effects. So we've established quite a body of information that will help women make a decision regarding surgery.

The other DoD grant that we had was an Idea Grant to study quality of life after prophylactic surgery. And what we found was while there were definitely some short-term differences between women who chose surgery and those who did not, short-term complications, the effect of immediate surgical menopause, the good news was that by the end of the year, after having surgery, most of these problems had resolved and there was no decrement in quality of life. And in fact, the women who had had the surgery, because of the relief of anxiety about getting ovarian cancer, actually felt better. They are concerned about the risk of early menopause and so they tend to wait until they're around 40, and we now have approximately 75% of women with one of these mutations eventually choose prophylactic surgery. So the numbers have increased considerably.

On the basis of our OCRP grant we competed successfully for an ovarian SPORE grant which is now in its thirteenth year. And we've been very involved from the very beginning with our families who are very much a part of the SPORE grant, and none of that would have been possible had we not had the original OCRP grant.