THE HEART OF THE MATTER
a special program of the National Emergency Medicine Association (NEMA) 

Week: 546.1 Guest: Dr. Joann Zujewski, Research Oncologist, Nat'l. Cancer Institute Topic: Breast Cancer Prevention Study Producer/Host: Steve Girard

NEMA: We've been spending some time with National Cancer Institute research oncologist Joann Zujewski...and during Breast Cancer Awareness Month, we wanted to talk about an area of study concerned with breast cancer prevention...tell me about that....

ZUJEWSKI: The breast cancer prevention trial is a study that was based on two observations...one is that, women who have received tomixifen...which is an anti-estrogen, developed fewer contra-lateral breast cancers. So, if you had a group of women who had breast cancer, and they took tomoxifen, there were fewer contra-lateral breast cancers developed. And so, based on that information and some laboratory data, which supports that tomoxifen can cause tumor regressions, and prevent cancer in animal models, a very large trial was developed with 16 thousand women...8 thousand in the placebo arm, and 8 thousand in the intervention arm. With the major end point of being breast cancer incidence. They're also in that trial, going to look at cardiovascular disease and osteoporosis, cause although we think of tomoxifen as an anti-estrogen, it has some estrogenic-like activities as well, so potentially they could prevent osteoporosis and heart disease. That's one of the major points of the trial. To be eligible, a woman has to be at least 35 years old and have the risk which would be equivalent to that of a 60 year old woman. Now, the average 60 year old woman has a risk of about one point seven percent of developing breast cancer in the five year period of the trial. So, anyone younger than that would have to have risk factors which would increase their risk to that of a 60 year old woman. For example, someone who has had a first pregnancy at a later age, or early menarche, or a biopsy which would perhaps have not a malignant lesion but a pathologic lesion... or new growth that would put them at risk. Now, that trial has accrued over 12 thousand persons to date. So the results of that should be out in the next few years as well.

NEMA: There's another trial which combines the efficacy of tomixifen with another substance...what is that all about?

ZUJEWSKI: What we're doing here in the intramural program is we have a small pilot trial where we are testing tomoxifen in combination with a retinoid, which is a vitamin-A analog. This particular retinoid is called fenretinide, because some animal models have shown that the combination of tomoxifen with fenretinide are more effective than either agent alone in preventing mammary tumors in animal models. We're also looking at fenretinide in preventing a secondary cancer in women...so we opened a small trial here involving about 25 subjects where we're looking at how the two drugs interact in terms of drug levels in the blood...or the pharmakinetics of it, but also looking at changes in the breast tissue itself, to see if there's any changes that we could use, for example, as a surrogate end point of breast cancer incidence, and this would help us do smaller trials of more promising agents in the future. For example, cholesterol levels are a surrogate end point for trials involving agents which might lower the incidence of heart disease and stroke. We're looking for similar types of changes in breast tissue in women that we can use as surrogate end points for trials of breast cancer chemo-preventive agents.

NEMA: Dr. Joann Zujewski of the National Cancer Institute, doing research for us on breast cancer prevention. I'm Steve Girard.