Christopher Gregg, PhD, investigator at Huntsman Cancer Institute and associate professor of neurobiology at the University of Utah, and Saundra Buys, MD, oncologist at the same institutions, talk about a novel approach to treating metastatic breast cancer.
Interview conducted by Ivanhoe Broadcast News in 2024.
Well, you are the first doctor I’ve ever talked to that I’m talking to as a patient and a doctor.
Gregg: Yeah, weird situation. But quite an interesting journey, to be honest. I have an understanding of the science network that I can call on to work on the science of the disease that I’m trying to solve myself.
Can you tell me how your journey started? First of all, I don’t think a lot of men are going to the precautions that women go to when it comes to breast cancer. How did you find your breast cancer?
Gregg: Yeah, you’re right. Most men are diagnosed with metastatic breast cancer when it happens at stage 4. It’s caught very late in the disease, and the outcome prognosis for men tends to be worse. I woke up one morning, and my nipple was bleeding on the left side. And I was perfectly willing to throw a band aid over that and go to work. But my wife was like, that’s weird. You need to go and get that checked. That took me on an extraordinary journey. I was living in Massachusetts at the time, working at Harvard, and I went to a doctor and they did a scan. They discovered that there was a tumor. It was a very strange looking tumor. They did a number of biopsies at the time, and they diagnosed the disease. Which means that it is localized, it has not spread throughout the body. It was very stressful. There’s something about hearing that word, cancer, when you’re just making your way through life. I was pretty young in my, I don’t know, mid 30s, I guess. But the doctor at the time assured me that this was no big deal. They were just going to cut it out. I get a mastectomy, which for a man is not a big deal, and I would just carry on with my life. I did get a mastectomy. And then years later, I had pains start to come up again in my spine and things like that. And I was going to a physiotherapist and saw many different doctors. I had a series of scans and imaging that were done and incorrectly evaluated and kept seeking out care until finally found a back doctor who did an MRI and found a big tumor in my hip and spine.
Can it just, like, help for those tumors?
Gregg: Yeah. On MRI, it would take up most of the vertebrae, the little vertebrae. It was several centimeters in size, I would say, at that time.
As a doctor, you know what’s going on, right? As a patient, then you take it to a whole new level. What goes through your mind knowing what you know?
Gregg: I knew that a stage 4 diagnosis with metastatic disease in different sites was a terminal diagnosis. I knew right away. I’m not an expert in cancer, or at least I was not at that time. I had published a paper that year — there’s great irony — in 2018 on why elephants don’t get cancer. Then a few months later, I was diagnosed with stage 4 cancer myself. I had a tremendous amount to learn about the disease going forward from there. It was quite a journey. I had essentially — some of the stuff is a little emotional. But I had the doctors at the Huntsman Cancer Institute went back and looked at the pathology that was taken when I was originally diagnosed back in Boston, and it was a mistake. There was an error. It had actually already spread. It was misdiagnosed as stage 1, and that misdiagnosis caused the disease to be let loose and grow uncontrolled for almost a decade. There were a series of other little medical mishaps along the way until I finally got properly diagnosed with cancer. That is probably not such an unusual journey for many patients, and about 30% of patients that get diagnosed with stage 1 disease, ultimately go on to develop stage 4 disease many years later. One of the things that I think about a lot about is how to improve that process and reducing medical mistakes and proper diagnosis for patients.
How were you treated? What was your treatment when you were diagnosed with stage 4 then?
Gregg: So then, the real adventure began. I went in and I got to meet with my oncologist for the first time, Doctor Saundra Buys. Just an incredible person. And she calmly took me through the results and showed me that I had all of these sites of cancer throughout my skeleton and said that the treatment would be palliative, which means there would be no attempt to cure. The treatment was just to extend life and maintain a quality of life as high as possible. On average, people live with that disease for about 3-4 years.
How long ago was that for you?
Gregg: Six years. I want to hopefully share with you a bit of the story about what’s going on there. So I asked my doctor at the time the question probably everybody asks their doctor, which is — are there any big miracle cures coming? What should I be thinking about in terms of therapies on the horizon, seeking optimism. She did not feel that there was going to be any big revolutionary cure on the horizon. It was most likely that we would get better at using the medicines we have.
Was that Dr. Buys?
Gregg: That was Dr. Buys. That was her professional perspective on the future of treating metastatic cancer. So I set about working on that problem in my spare time, essentially, and was able to uncover an article by a mathematical oncologist at the Moffitt Cancer Center named Bob Gatenby, and Bob had discovered ways of modeling cancer with math that were inspired by how species go extinct and how farmers use pesticides to control pests in their fields. These were incredibly creative insights, and what Bob had recognized was that farmers were dealing with the same problem that oncologists were dealing with. A patient would be put on a chemotherapy, and it would work initially. And then the cancer would become resistant. You would have to stop the drug, go to your insurance company and say, look, I’ve shown progression on this medicine. Can you give me a different drug? And the oncologist would pull out a new drug, and you get a response initially. But then show progression again and eventually run out of drugs. And the patient dies because you can’t control the disease anymore. So, in farming, there’s a similar problem where you’ve got pests destroying the crop, and you’ve got pesticides that you can apply. But the agricultural community has what are called treatment resistance management plans. These are ways of using the pesticides that prevent the pests from becoming resistant to the chemicals, and they have a number of very simple rules. One is that you try to minimize the use of the pesticide. So you try to use other approaches that are not dependent on chemicals to control pests in the crop, you rotate the chemical classes of the pesticides, you’re never chronically spraying with the same chemical until everybody develops resistance. So you’re constantly switching it up all the time. Then the third is that if you start to see resistance in your field among the pests, stop spraying and let the susceptible pests come back. They will start to grow and take over the population. And then you can spray again, and you have control now again over these pests in your field. So we had these three solutions that were working well for controlling this resistance problem, and we in cancer could be learning from that to prevent the development of treatment resistance in cancer patients because the current treatment regimen is essentially what a farmer would find would immediately cause resistance. You treat with the same chemical chronically at the maximum tolerable dose until progression. That’s essentially causing resistance to happen in every patient.
Is that the birth of the extinction therapy?
Gregg: Yes. That’s right. This was the birth of this concept that Bob and Joel Brown and Sandy Anderson at the Moffitt Cancer Center had been working on. I invited them to come to the Huntsman Cancer Institute. So we got this small symposium within a few months of me diagnosed. We talked about these ideas of how to use evolution and lessons from farming to improve cancer care so that patients could stay on their drugs for very long periods of time and not become resistant to the medicines. So that little conference was a big moment for me. I mean, I was in tears at the end of the conference. There were other patients in tears at the end of the conference because it was a glimmer of hope that you could use the medicines that were all approved. You didn’t have to wait 20 years for some new cure and solve this problem. The conference was in, I think April or May. And then in June, excuse me, in late August, I started myself on extinction therapy.
And you were your own lab rat?
Gregg: I was my own lab rat. And of course, as somebody who does run a lab with many lab mice, the irony has not been lost on me.
And what was that like? I mean, you believe so strongly in this. Was there any trepidation?
Gregg: There was a lot of trepidation because, well… There was some trepidation because one of the risks was that by going through extinction therapy where I treat myself with many different drugs. At the end of that, two things could happen. One is that I’m so sick because I’ve taken all these toxic therapies that it’s very hard for me to maintain a quality of life or even to go on further treatment. The other is that I could build a horrible monster cancer cell that’s resistant to all of the available treatments, and then I would really be in a pickle. So it was at the time a huge risk, but there was a lot of thought that was put into this idea. And the idea makes sense to me and it had been proven in the farming community that you could use these types of strategies. For many reasons, it made a lot of scientific sense to me. And somebody essentially had to try it. Somebody had to try it, and that’s the way.
Five years ago was this?
Gregg: That was in 2019. So I rapidly reached what’s called NED, on that treatment protocol, which is no evidence of disease, which meant I got a complete response. Essentially they could not detect hardly any residual disease in my body. That’s very rare in my type of cancer. Only 6% of patients would achieve that. And I was in that state for nearly four years.
And you didn’t have to take any more drugs or anything in that four years, right?
Gregg: I did. I was taking drugs and jumping from chemical class to chemical class, just little spurts of different drugs. But I never progressed. The key is that I never progressed or became resistant to 11 different drugs over all of those years. So the treatment resistance management plan was working just like it would work in the farming community. Now, at the end, I tried an experimental drug and the cancer came back suddenly, very quickly, within a month. And we don’t really understand it. It’s not normal progression. It’s as though the drug itself had somehow contributed to the cancer coming back. I think as a scientist, just recognize that when you’re the first astronaut going through some of these things, it’s not going to be perfect the first time. And we always had a backup plan. The backup plan was to use these principles from farming to manage the cancer. So I knew that if the disease came back, what we would do next is we would allow the susceptible population to grow back again. Take a break from the treatments. And the big question was, had I trained a monster that I couldn’t treat anymore? Or would I still be responsive to the very first line treatments that a patient would initially be given? And the answer has been, I’m still responsive to those very first line treatments. So I’m back on tamoxifen and Verzenio, which would be the very first treatment a metastatic breast cancer would typically get treated with. And I use nutritional interventions as part of my integrative management strategy to reduce the use of chemicals in my cancer care pathway. And so far, this has been very effective. I’ve been stable, and for much of 2023, I was completely off of treatment.
When you first met Dr. Gregg, where was he at his cancer journey?
Buys: He had just found out that he had metastatic cancer to the bone. So it had been some years since he had the original cancer. He’d been having pain, and then it turned out that it had gone into his bone.
When you have patients like that, and for Gregg, what is their treatment? What is their outcome? What is their future?
Buys: When patients have metastatic breast cancer to bone, I usually talk to them about this being something that we can usually control for some years, but it’s not usually a cancer that we can completely eradicate. We talk about the treatment, starting with the easiest treatment possible that has a likelihood of benefit And that would be hormone blockers, and then we kind of escalate through different lines of hormone therapy until the cancer becomes resistant. And then we would start on chemotherapy of a variety of sorts. So that was the plan that I laid out for him.
So when did you know there was going to be something a little bit different about Dr. Gregg?
Buys: There are a lot of different things about him. Number one, he’s a man. Number two, he’s really an extraordinarily wonderful individual. But within a few months after I first saw him, he had talked to various people and decided that maybe the standard treatment was not as good as we could do, so he brought these crazy ideas to me, and they made sense. I thought, well, it’s all FDA approved. We’re not doing anything totally that’s out of whack for breast cancer treatment. So I thought, we’ll try it.
When you tried it, and it started working, and it started working really well. I mean, did that change the way that you had been thinking before?
Buys: I’m not sure. I think that for someone who is really committed to using intensive treatment, this is a reasonable way to go. I still don’t think we absolutely know that things would have been different if we’d done it the more traditional way. I think now it is unusual that he’s out this far and doing this well. The treatment that he had for the first nine months or so was really hard. And ordinarily, what we would do is start with easy treatment and continue on the easy treatments for as long as it keeps the cancer under control. Eventually, we need to go to the harder treatments. But as you know from talking to him, what we did with Dr. Gregg is start with really aggressive treatment to see how much tumor regression we could get. Then we continued really hard treatment, number one, really hard treatment, number two, really hard treatment, number three. So I think that that first year or so, his quality of life suffered because of the treatment. But I do think that now we are seeing pretty good evidence that he’s doing better now than I would expect for somebody who’s out as far as he is. So I think by hitting it hard initially, we may have gained this additional time that we’ve got now, with him feeling pretty well. I can’t say that I was a convert immediately just because the treatment initially was harder than it ordinarily would have been.
And that he’s a researcher, and then he tried this. I mean, it puts him in a field on his own.
Buys: Well, yes. The other thing about Chris is that he really has managed to identify people around the country who are really on the forefront of this new way of thinking about cancer. He’s been very talented, really quite gifted, at making contacts. And he’s just such a nice person. Anybody who talks to him wants to do the best we can for him, as we do for any patient. But for somebody who’s so committed to making a difference for his own cancer and also for other people, it’s appealing to work with him.
I would think being a person who sees all stages of breast cancer all the time, every day, it’s nice to just have another tool in that box that you might be able to offer patients?
Buys: It does feel empowering. And I’ve started talking to patients about this. Maybe there’s a different way, maybe there’s a better way that we can treat it that just takes advantage of some of these things that we can learn from other fields of science and biology. So I think it’s really exciting.
And worth pursuing to the next level?
Buys: Yes, definitely.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information, please contact:
Steve Lee
Sign up for a free weekly e-mail on Medical Breakthroughs called First to Know by clicking here
