University of Iowa researchers recently discovered a gene that plays a key role in the ability of breast cancer cells to respond to estrogen. Ronald Weigel, MD, PhD, professor and head of the Department of Surgery at University of Iowa Hospitals and Clinics and the lead in the study, talks about the gene and the study:
Tell us a little about the genetic study. What was the purpose of the study?
For a number of years now, we’ve been very interested in trying to understand why a breast cancer cell would respond to hormones such as estrogen. And that’s critical because some of the mainstay treatments for patients with breast cancer are drugs like Tamoxifen and the newer aromatase inhibitors that work through targeting mechanisms of estrogen response. Our study was centered around trying to understand what regulates hormone response, meaning why do some breast cancers respond to hormonal therapy and others do not?
Who participated in the study?
My lab was primarily involved in this study and included my research assistant, who was the first author of the paper, George Woodfield; a post-doctoral fellow in my laboratory by the name of Dr. Yizhen Chen; and a previous post-doctoral fellow I had in my lab, Dr. Anna Marie Horan.
What did researchers find regarding the ability of breast cancer cells to respond to estrogen?
What we were able to do was to identify a novel mechanism of hormone response. There is a gene which is a transcription factor, it’s a protein called TFAP2C. I know that there’s a lot of alphabet soup there, but what that basically means is that’s a name that we give to a certain protein which has the ability to go into the cell and turn on different genes. And what was found was this gene, TFAP2C, is a central switch that turns on the mechanisms of hormone response in a breast cancer cell.
Why is this genetic link important in the fight against breast cancer?
One of the reasons why we’ve been very interested in this study is because, as I’ve said before, drugs like Tamoxifen and aromatase inhibitors that target the estrogen receptor pathway really serve as the mainstay for treatment of women with breast cancer.
However, these drugs aren’t effective in all individuals. There are certain people who don’t respond to these drugs and certainly a whole class of tumors that don’t make estrogen receptors, which don’t respond to these drugs. By our ability to understand mechanisms that induce hormonal response, we’re better able to do two things. One, develop new drugs that can treat women with breast cancer that respond to hormone, and the potential of inducing hormonal response in an unresponsive cancer so that those women would then be responsive to drugs like Tamoxifen.
What does the future hold for this, kind of putting this research into a clinical situation for women in Iowa?
We certainly hope that over the next several years, we can begin to exploit this pathway caused by this transcription factor as a new method of treating women with breast cancer. So the ways to do that are two potential ways. One would be to target this transcription factor by finding drugs that inhibit it and therefore stopping the growth of hormone responsive cancers. The other approach we might be able to use is to induce the activity of this factor in breast cancers that don’t normally make it, and thereby induce hormone response in those tumors.
Are there other ongoing studies at University of Iowa Hospitals and Clinics with regard to breast cancer?
Yes, we currently have a tremendous program which is in a push here to advance breast cancer treatment at The University of Iowa. We are soon going to be opening a new breast health center to take care of women with breast problems, both benign breast problems as well as breast cancer. And there are a number of parts of that whole center that we’re putting together, this sort of research and what we call translational research, meaning taking the new findings that we’re finding in the laboratory and bringing them to the clinical treatment of breast cancer patients is a major effort that we’re currently making at the University.
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