Chapter 05: Creating Research Collaborations Focusing on Breast Cancer

Chapter 05: Creating Research Collaborations Focusing on Breast Cancer

Loading...

Media is loading
 

Description

In this chapter, Dr. Buchholz explains how he found his research niche with the breast cancer group because the radiation oncology dimension of breast cancer treatment at MD Anderson and in the field had not yet been established. He began to use his skills to establish research collaborations that resulted in over one hundred publications that influenced treatment and the field of radiation oncology. Dr. Buchholz describes several of his research collaborations and the projects he worked on.

Identifier

BuchholzT_01_20180110_C05

Publication Date

1-8-2018

Publisher

The Making Cancer History® Voices Oral History Collection, The University of Texas MD Anderson Cancer Center

City

Houston, Texas

Topics Covered

The Interview Subject's Story - The Researcher; The Researcher; MD Anderson Culture; Research; MD Anderson Impact; MD Anderson Impact; Building/Transforming the Institution; Multi-disciplinary Approaches; Collaborations; Leadership; On Leadership; Understanding Cancer, the History of Science, Cancer Research; The History of Health Care, Patient Care

Transcript

Tacey Ann Rosolowski, PhD:

Now, we hadn’t—I hadn’t asked you how your focus on breast cancer came about.

Thomas Buchholz, MD:

It came about, in part, because of opportunity, I think. I had published a breast cancer paper in Seattle that had gained some national traction. And then when I came and looked at where professionally I could have the biggest impact at MD Anderson, I thought, wow, this is a group that sees a lot. Gabe Hortobagyi [oral history interview], who’s the Chair of Medical Oncology—he’s an internationally renowned person, and they’re doing interesting clinical trials. So the multidisciplinary structure is there. It’s just the radiation oncology piece hadn’t been fully developed. And so I thought, this is perfect. It was a subsection, again, back to the relationship component of being a doctor that I really liked, that you tend to have very intelligent people who are going through a hard period in their lives. So I liked the patient care aspect. It was interesting, again, intellectually, biology, technical, treatment delivery, etc. So it just proved to be a good fit.

Tacey Ann Rosolowski, PhD:

Now, I... When I was doing some of my background research online, I found an article, or an essay, that you wrote, “Preparing for the Future of Radiation Oncology,” in the Journal of the American College of Radiology. And it was really interesting. I pulled out a couple of quotations. And you were talking about how it’s only through translational research that radiation oncology can expand its role, and you were expressing the concern that radiation oncologists really need to develop those skills so that radiation oncology doesn’t simply become a service that isn’t contributing to the advancement of cancer science.

Thomas Buchholz, MD:

Yeah.

Tacey Ann Rosolowski, PhD:

And what I’m kind of hearing you say right now (laughs) is that when you took the job at MD Anderson, I mean, you weren’t looking at the entire field in that way, but you kind of had, yeah, I want to make a contribution in that way.

Thomas Buchholz, MD:

Yeah, yeah.

Tacey Ann Rosolowski, PhD:

So that came real early for you.

Thomas Buchholz, MD:

Yeah. It was... It was great. I mean, it was—one of the really appealing things was Dr. Meyn in experimental radiation oncology, and then I started hanging out with these lab people, and I didn’t have to run the lab myself, right? Because they were PhDs, and they were very smart. And I didn’t know they would be welcoming someone from the clinic, but there weren’t too many doctors at that time who were going up into the labs, and they thought it was great. So I did form collaborative relationships, and I did start writing grants, and I’d start getting funding, as a principal investigator. And I tried to do things that would use human tissue, and bring it into the lab to build on science that they were doing on cells and animals, and give it a different degree of relevancy. And so I based a lot of... So when I got to MD Anderson, I just kind of went for it. I didn’t have any startup funds. I didn’t... But I had the courage, like my dad. I just kind of went for it, and I got involved, and I said to—“Wow, you made this observation in mice? Has anybody looked at that in humans?” “No, how would we look at that in humans?” “Oh, there are all these patients getting that same chemotherapy that you were studying in mice. Maybe I’ll just get some tissue from them.” “You could do that?” “Oh, I guess so.” And I’d write a protocol, and... Well, how you—nobody asked how you were going to pay for it, or so, okay. And then I’d write a grant, and I’d get a little money here, and a little money there, and it was kind of naïve courage, I guess, (laughs) because I started to do all sorts of translational studies. And by not owning the lab component of it, I could diversify, and I did a whole bunch of different avenues with three or four PhD collaborators.

Tacey Ann Rosolowski, PhD:

What were some of the projects you worked on?

Thomas Buchholz, MD:

The first was looking at a genetic predisposition to breast cancer, with a gene that had just been cloned called ATM. The second was looking whether chemotherapy-induced apoptosis was predictive for chemotherapy ultimate response and survival, and what are the biomarkers that influence that, and what are the chemotherapy agents that do. So I started to do biopsies of people—breast cancer patients getting chemotherapy before surgery, to show kind of early changes in tumor cells. That’s a very frequent approach now. Even that’s—Dr. DePinho [oral history interview] brought that out as an Apollo Moon Shot or so, but I was doing it in 1998, in 98004, my human subjects protocol. And it was fun, because it got me into collaborating with some of my medical oncology and eventual pathologies that started to look, then, at gene array expression, which, again, is very common now, everybody does it, but at that time nobody at MD Anderson was doing it at all. We had to collaborate with Millennium Pharmaceuticals, because they were very interested in these data. So we—I think we published the first gene set of serial biopsies during chemotherapy in breast cancer.

Tacey Ann Rosolowski, PhD:

Now, I’m afraid I’m very ignorant about what piece you as a radiation oncologist would bring to a study of that kind.

Thomas Buchholz, MD:

Well, that’s a great question, (laughter) I guess, right? Because it was just... For that particular study, just nobody else was doing it, and so I said, “Let’s do it.” And I had some collaborators in medical oncology. They weren’t doing biopsies, either. We didn’t have the same infrastructure in 1998 that we do now, so nowadays if I was going to write a protocol like that, it’d be a little bit more awkward, because there would be a medical oncology patient, and the pathologist would be doing the biopsy, and this would be analyzed in here. “Well, what are you doing?” At that time, we were a smaller group. I would be going to every multidisciplinary clinic. I would be meeting with the patients. I would be convincing them. I didn’t even have a research nurse. I’d be signing them up to the protocol. I went and learned how to do a biopsy from a pathologist. I bought my own biopsy guns. I bought my own lidocaine. I did this. I’d convinced the patients to stay for 72 hours in a hotel, and I’d personally do all these things, and then I’d take the specimens over to the pathology myself. And so I was kind of the one doing all the work with the study. This genetic predisposition to breast cancer, again, it’s not a real radiation question, so... But I was the one identifying the patient populations. I drew their own blood, right? We didn’t send any to a lab. I bought my own phlebotomy tubes (laughter) and bring them. That was kind of how you did it in the Air Force, right? And I thought, well, that’s how you do it in MD Anderson, too. So—

Tacey Ann Rosolowski, PhD:

So you were really facilitating this translational work.

Thomas Buchholz, MD:

Yeah, exactly.

Tacey Ann Rosolowski, PhD:

Yeah, yeah, you were the glue holding it together.

Thomas Buchholz, MD:

I was the glue, right. And I’d often come up with the questions, and I’d write the grant, and I’d get the money, and...

Tacey Ann Rosolowski, PhD:

Honestly, what a blast. (laughter)

Thomas Buchholz, MD:

It was a blast. It was. Yeah, we started studying BRCA carriers, and whether they have BRCAs involved in double strand break repair, and I wanted to see if they had deficits in that in the laboratory, so you get a little tissue and you could grow it in culture and study the DNA repair process, and in the setting of a BRCA mutation. In the laboratory you could radiate their cultured cells, and... So we did a lot of projects, and everybody would tell me, “Oh, you gotta... Tom, you’ve got to focus,” right? And it’s true to some extent, and that’s a good mentorship advice to an assistant professor, because if you have ten projects, and say you get ten preliminary datas, and they’re all positive, to carry them forward gets to be a little bit challenging. So a lot of these things got to a point and I kind of dropped off. But I didn’t really want a sustainable lab career, too. I was kind of... So, I don’t know. (laughter)

Tacey Ann Rosolowski, PhD:

You were sort of riding shotgun in between. (laughter)

Thomas Buchholz, MD:

I was. I mean, I had a whole variety of collaborators within the scientific institution: people outside of our department, people inside of our division. So it was fun. It was really fun, and I was really caught up in this microarray gene expression. That was, I remember, so much fun, sitting with the bio informatician and trying to analyze these gene sets with—we didn’t have the software that’s available now. And at the same time, too, I did—if you look over my CV, it’s mostly about clinical publications. And you mentioned I was interested in education from the onset, and so I ran our medical student program, and became then residency program director. And I really wanted to give younger people the opportunity to do clinical research. And so then you have success if people see, wow, you could get a good project with Tom, and you could—he’ll let you publish it, and he’ll be—you could be a first author on it, and... So, again, when I was an assistant professor, I kind of hit my stride, I think. I would be working with five or six residents on a variety of different projects that were more data based, and I had these lab collaborations going, and I was running the residency program. I was the busy—one of the busiest doctors, taking care of patients. And it was just fun, right? It was a really, really fun time, intellectually fun, and... And I was getting along. There was no politics. There was a little politics, I guess, when I first got started about—inevitably, whatever you do in academics, you kind of get into potential turf battles, or, “Well, I was going to do that project,” or... And there was a little—probably some of the more senior people on our service were kind of saying, “Wait,” right? But it all worked out. I think, in the end, again, that ability to connect with people and have relationships with people and be inclusive and have everybody win, and not be competitive, and listen to good advice, but still not let it inhibit you from moving forward. So it was a blast. I really had a great junior faculty time. And I had a great boss, Jim Cox. He thought the world of me. I was a high-performing faculty. I was publishing tons of papers. I was bringing in grants. At that time, nobody in our department, except for Kian, was really bringing in grants. I was very busy clinically. I was getting along great with all the medical oncology and surgeons, and they were saying to Jim, “Oh, Tom’s been such a great...” I’d show up. They’d have protocol meetings. I’d just show up, and I’d participate. And they’d have a journal club, and I’d show up, and I’d say, “Hey, I got a great article. Let me present that.” So I was an engaged member of their group in a way that they never had had before. And they loved it. And I, of course, then benefitted from those types of collaborations, too.

Tacey Ann Rosolowski, PhD:

What do you think you were teaching them about what radiation oncology can do?

Thomas Buchholz, MD:

Well, I think I taught them quite a bit, actually, right? Because just sharing—we are kind of in the basement, and nobody knows the technical aspects, and so people were concerned, oh, radiation causes heart disease, which it did for a long time, but now we could overcome that through technology, and as long as you don’t treat the heart you’re not going to cause heart disease. And we could... So I could help educate. Some of these historical things aren’t the same as they are in modern days, and this is why we should think differently. I think, more importantly, I also taught them that there are a lot of other important questions that are outside of their viewpoint. And so one of the best resources I had was the medical oncologist did a whole series of clinical trials here that had a very rich population of people treated with chemotherapy before surgery. And nobody else in the world—MD Anderson and Gabe [Hortobagyi] and Aman Buzdar [oral history interview], they were really thought leaders. Now everybody in the world does that, but at the back end of that there’s all sorts of questions about should you get radiation if you have a really good response, or does radiation work if you have a really bad response. And this was the most powerful collection of data to address real questions. And none of them were thinking about these questions, because that’s not their profession, where they were so obvious questions to me. And so then we could look into the data and find not definitive answers but find the best answer that would be available. And I think that’s what else I taught them was we started—I said, “Let’s collaborate. We’re going to ask these questions. Let’s use your databases. Let’s augment them with the necessary data.” And there were literally a hundred papers or so we wrote over time on this topic. And it really opened their eyes as to, wow, these are really relevant and important questions that... And we’re the leading institution now that has this, so... Eventually, I chaired the NCI Statement of Science about local, regional questions associated with that. And I started working in the cooperative groups with—to address prospective protocols on the basis of those. So, again, what a goldmine for me as an assistant professor to come in and have access to those types of important clinical questions that are nowhere else in the world.

Tacey Ann Rosolowski, PhD:

Now, you mentioned some of your collaborators. Who were some of the other people you worked with that were really important?

Thomas Buchholz, MD:

Kelly Hunt, I think, is probably one of my best collaborators through the years. We—she’s a Chair of Breast Surgery. And so our local regional treatments kind of complement one another. Kelly, during her fellowship here, generated big databases that she so willingly would share with me. She was a wonderful collaborator in that she and I never had a political moment. (laughter) She was interested in the science and the team, and I was interested in her career, she was interested in my career. And so she’s been a fun collaborator. Gabe, certainly from the medical oncology standpoint, but there’s a number of other of his colleagues from Vicente Valero, and pathology. I worked with Aysegul Sahin and Fraser Symmans. There are a couple medical oncologists who have left, like Lajos Pusztai, who did this microarray work with me at the onset. He was a fellow. And Massimo Cristofanilli and I started the inflammatory breast cancer program here. And so there was just a number of great collaborators over 20 years. And then, of course, now in Radiation Oncology I have the greatest—I’m part of the greatest section ever. We went from three of us—and I’ve got to give credit to Eric Strom, as one of... Eric was—is the faculty member on our service in Breast Radiation who was—he had been faculty member five or six years before myself. And Eric taught me so much about clinical radiation oncology, and caring for patients, and he’s still someone that I have a great relationship with, and have deep respect for. So he’s still on our faculty, but our other nine faculty members are all people that I mentored and hired, and boy, they’re bringing our group to even new levels now. Now we have such a portfolio of radiation contributions coming from a whole variety of different avenues, and so it’s been really fun to watch.

Tacey Ann Rosolowski, PhD:

Because you’re watching the institution, you’re watching the careers, and you’re watching the whole field grow.

Thomas Buchholz, MD:

Yeah. And in ways—Wendy Woodward, who’s now my section leader, Wendy and I must have published four papers together when she was a resident. And yeah, and she brought new dimensions. She’s a real physician-scientist, and a really outstanding MD/PhD physician-scientist. And so while I helped her mentorship in some clinical things, she’s also broadened kind of our contributions in biology in a way that I never can claim any mentorship to. (laughter) She really has got a skillset that’s much more diverse than mine, and it’s been awesome. Ben Smith I hired, too. He’s truly an outstanding academic radiation oncologist, and he brought a whole expertise in health services research, again, and statistics, and in a way that, again, he’s mentored me more than I mentored him in some of those academic aspects. And they’ve been great collaborators, just within our group now, and we have such a great group. And it’s been fun to get back working with them again.

Conditions Governing Access

Open

Chapter 05: Creating Research Collaborations Focusing on Breast Cancer

Share

COinS