Dr. Antonio Wolff talks to BCRF about how collaboration is key in the fight to solve breast cancer
It takes a village to understand and solve breast cancer. In this case, the village is more like an innovative network of research labs, scientists, patients, funders, and more. In other words, something like the Translational Breast Cancer Research Consortium (TBCRC) led by Dr. Antonio Wolff. The TBCRC is a collaborative group founded in 2005 to conduct innovative and high-impact clinical trials for breast cancer.
In this episode, Dr. Wolff shares how collaboration across disciplines, institutions, and countries is key to attacking the disease. Dr. Wolff’s work, along with others, has helped design, implement, analyze, and report clinical trials. The goal of these trials is to provide insight into the development of more effective and individualized treatments for breast cancer. Results provide crucial insights that guide personalized treatment for various subtypes of breast cancer.
The numbers are impressive: TBCRC is comprised of 19 clinical sites and five working groups that have launched nearly 50 studies. These breast cancer investigators share information, data, successes, and even obstacles, as they frequently coordinate their efforts toward their common goal.
Dr. Wolff, a BCRF investigator since 2007, is a professor of Oncology at John Hopkins University and a member of the Johnson Hopkins Kimmel Cancer Center in Baltimore, MD. He received his medical degree at the Universidade Federal do Rio de Janeiro in Brazil and trained in medical oncology at Johns Hopkins. He is an associate editor of the Journal of Clinical Oncology, chair of the ECOG-ACRIN Breast Cancer Committee, and chief operating officer of TBCRC.
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Read the transcript below:
Chris Riback:
Dr. Antonio Wolff:
Chris Riback:
Dr. Antonio Wolff:
Chris Riback:
Dr. Antonio Wolff:
And so Twitter has been, I find it awesome. Because it gives it us the opportunity to reach out to the public directly and it forces us to be sharp in our thinking. So I will say that actually Twitter and other forms of communication and I can tell you, I use Twitter professionally. I don’t use it for personal uses––it forces me to more clear in my communication and the feedback we get gives you the opportunity to better understand if what you as a researcher think is interesting really matters to the people for whom this should matter the most. It’s a great platform.
Chris Riback:
Dr. Antonio Wolff:
Chris Riback:
Dr. Antonio Wolff:
Chris Riback:
Dr. Antonio Wolff:
And these meta-analyses proved to be incredibly helpful to allow us, for instance, in the mid-1990s, it took us a long time to begin to realize that as one concept, adjuvant endocrine therapy, the use of a drug called Tamoxifen for women with estrogen receptor-positive disease and till 1995, there was a belief that these medications, Tamoxifen did not help women with early-stage breast cancer, did not help improve their survival. It was only after one of the Oxford Overview Meta-Analysis published in 1995, doing exactly what I just described lumped in together a lot of similar sized studies that the effect became obvious and that changed clinical practice.
We, the NCI, with the war on cancer in the 1970s and many key investments in the 1980s was funding in the US a number of what we call cooperative groups. At that time SWOG, NSABT, CALGB, ECOG, and a few others, NCTTG, as well, and these groups were doing a lot of studies, especially, the adjuvant study, many studies, a study of disease as well. These were studies that required several hundred patients and many went on to change the clinical practice in breast cancer in early stage in advanced disease. But the amount of funding available at that time allowed many more ideas coming from these friendly competitive groups where you’d kind of nudging each other, challenging each other to do better and better because your best friends are also competing with you.
NCI always very supportive of us doing these types of studies, but they were time-consuming, took a long time, but also allowed a whole generation of investigators to be trained and to become very good at designing, implementing, analyzing, and reporting clinical trials and improving more and more their ability to communicate with the public, which goes back to what we discussing moments ago.
Chris Riback:
Dr. Antonio Wolff:
What I mean by that, we had the ability to do more blood tests, collect more blood samples from patients on trials. We were able to potentially do research biopsies. So someone with early-stage or metastasize, we would ask patients to volunteer to donate a tissue sample, to allow a research biopsy of breast tissue or a site of metastasize in an organ like the liver or lymph node. These are more costly. These are more time consuming, and it was becoming difficult to do these types of more bio-specimen intensive trials within the cooperative group systems because the level of funding available for those types of bio-specimen collections was simply not available.
The NCI would provide us for the most part with resources to run the study, to test new treatments but we always had to go elsewhere to figure out how to collect the specimens. So we had a situation, why did we do the TBCRC? We had a situation where we had the cooperative system was allowing us to do, still very important and practice-changing trials by asking simpler questions and we had a lot of new ideas that required a bigger dive into the details as I mentioned with correlative studies, using blood and tissue specimens. And we figured out that we needed something in between instead of doing the large studies, we had to cooperative groups, or the much smaller trials and more intensive with one or two institutions.
We realized that we actually needed to have something in between where we could bring together three, four, five, six, up to 10 institutions at a time, joining a study where we could do what we were doing within each of our institutions but in a larger scale with more patients and taking advantage of the broad expertise that we all have to design the best possible studies and I think that this is one of the critical things about TBCRC … the ability to give junior investigators the opportunity to present, propose their ideas to more senior investigators, hone their skills, improve the quality of their proposals and design the best possible studies, so that we could continue to develop the pipeline of junior investigators that one day would become senior investigators and I with others am a perfect example of individuals that grew up in that system.
Chris Riback:
Dr. Antonio Wolff:
Chris Riback:
Dr. Antonio Wolff:
What we have done, and we are as you said a center, we function as a center without walls. We have been able with trying to keep us nimble without physical locations, but taking advantage of the tools available for communication, we have hired a couple of individuals who serve as business managers and program managers and protocol coordinators, who are individuals who help keep the glue together. Most of us are academic researchers with expertise in medical oncology, surgical oncology, radiation oncology, laboratory science, and then we bring the people who help. We, scientists, dream of the studies we want to do, but then we need individuals who are going to make it happen logistically so we have protocol coordinators. We also need individuals who have expertise in legal issues, contracting, and finances, because all of this takes effort and I often say, “No money, no mission.”
Chris Riback:
Dr. Antonio Wolff:
And just to give an idea, working groups, we have working groups focusing on Triple-Negative Breast Cancer, focusing on Estrogen Receptor-Positive Breast Cancer, HER2 Positive Breast Cancer. We also have working groups focusing on, we call it Loco Regional issues, so a number or surgeons and radiation oncologists and then recently, we also added an Immuno-Oncology interest group. We get together by phone. We have identified among us individuals with expertise in bringing people together, they function as co-chairs. We have a patient advocate represented in each of these working groups. We have a clinical trial methodologist, statisticians as well, and so we on a regular basis, we propose a new idea that we think could be an important idea in answering questions that we have about issues we are facing in the clinic. Anyone of us can bring a new question, a new idea.
Do we have something here that could potentially be addressed in a clinical trial? Then through an iterative process, an idea is discussed and we think about what would be the best clinical trial design to address that question. Usually, the person who proposes that idea becomes the champion and others begin to offer ideas and collaborate and through over a couple of months, very quickly we may have the opportunity to develop a clinical trial and I think it goes back to the points that we were making before, it is so important to have us more or less on standby.
We know that every month, on the same time, on the same day of the week, we’re going to have a phone call and we have organizers and coordinators that help us with agendas and minutes so we know exactly what conversations that may need to happen in between conference calls. And we gradually, this gives an opportunity for junior and mid-career investigators to immediately get feedback without having to wait for a study section to provide feedback in a couple of months, but we almost immediate feedback of an idea, whether this is a good idea, not a good idea, or an idea that needs refinement and then we can take it to a steering committee of about 10 people with more senior individuals with a lot of experience and then we can figure out how best to make sure that the question we’re asking is relevant and let’s figure out how we’re going to fund this through philanthropic funding or sometimes partnership with industry. Because in many cases, they have access or control individual drugs of interest and how ultimately, we make it all come together. It goes back to the same challenges we’re having–we need to have people available and ready to handle a new challenge, rather than creating something that doesn’t exist.
Chris Riback:
Dr. Antonio Wolff:
Chris Riback:
Dr. Antonio Wolff:
That is the same answer I give to many people who ask me, “It must be so difficult to be a cancer specialist.” My answer is, “I don’t think I could have done anything different or anything better than what I do.” Because that’s part of the reason why I made a conscious decision in my training as I was doing, I was a laboratory researcher during part of my training, learning laboratory skills, and the challenges of doing science in the lab.
I very quickly realized I have, I like being around people. It is a privilege that patients give us. They open a window in their lives, in their most personal issues and fears and give us the opportunity to go in there and we have a responsibility then to help them the best way possible. So in this, the trajectory of being a medical oncologist as I am applies to any other medical discipline. The issues are, they cover a whole gamut, because it is, “Do we have the best diagnostic tools? So we can make the correct diagnosis.”
So not until then will you find exactly what is going on and then you can come up with a plan of action and then you need to figure out whether the tests are appropriately developed and giving you accurate information and whether that is an imaging test, an MRI, a PETCT, whether this is a blood test, you don’t have false positives and false negatives, and you make sure that the tests are really doing what they’re supposed to do. Then we have treatments that we need to find out or is this new treatment going to really help or is this treatment going to just have toxicities, be its side effects, but sometimes also financial toxicities and cost.
Do they have not only efficacy but also effectiveness? Do they improve outcomes compared to other treatments, and then we have once you treat someone, I often tell my patients, especially patients with early-stage disease, “I am going to be your doctor for a while, but my hope is to become the doctor in your past so that you can finish your treatment for early-stage disease and I’ll be able to help you move on with the rest of your life and hopefully, you will even come to the point that you forget that at one point you had cancer and you can move on and have your relationship with your primary care physician and do everything that you want to do and forget about me and forget about all of this.”
Then obviously for some patients, with advanced disease, we may not be able to cure their disease and allow them to forget about this, but we can hopefully improve not only their quantity of life but also their quality of life. So that they spend time with doing what is important for them, whether it is to work, to study, to retire, to see children graduating, growing up, and falling in love to live a full life as much as possible. For patients with an incurable disease who unfortunately will die from the disease, help them during that transition.
But the type of work that I do touches, as I said, I am interested in anything related to breast cancer. Anything that could in one way or another improve the quality of the work we do, improve our ability to help people, and that is one of the things, why being a researcher in breast cancer and being a part of this, one example is TBCRC, it is such a privilege because I am surrounded by smart people and it just kind as I often joke, it raises my IQ. Just being, surrounding myself with very smart people who are going to challenge me to do my best is almost like a sports team, a sport competition. We’re going to be better, practicing together, training together.
Another point, even within TBCRC and in other groups as well, we have probably, we are one of the groups of the largest number of patient advocates in it. So within TBCRC and in other groups as well, we have probably, we are one of the groups with the largest number of patient advocates in it. So within TBCRC, we have 19 institutions, a criteria for membership is that we need to identify one patient advocate from each institution, to come and join us. When we get together, we have 19 patient advocates in the room.
Chris Riback:
Dr. Antonio Wolff:
The BCRF has been able to be a conduit by an incredibly talented, inspired, motivated group of individuals, some of them scientists, others not scientists, but individuals with the public good in mind, and to channel the work by volunteers, the work of philanthropists, the work of individuals, many of them who are very wealthy, others who are not. Individuals who are interested in helping, in figuring out, “How can I use my dollar, my resources, and potentially make sure that this is well used. So BCRF brings it all together and providing, developing resources, I often joke, “We know that every vote counts. Every dollar counts and it adds up very quickly.”
And with its scientific leadership, people who can pay attention to many of the challenges and health issues and ideas challenge us, researchers, to think about new ways, novel ways in a manner that has not been done before, and with all of that, the BCRF is not simply writing checks and doing fundraising in their various events but they’re spending a lot of time with us, listening to what we scientists are saying, doing what you’re doing today as a non-scientist, trying to understand what we do and then wearing the hat of the public, helping us put ideas together, not only to explain to the public but also to make sure that the work we do has relevance.
Chris Riback:
Dr. Antonio Wolff: