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Dr. Larry Norton Highlights the Progress and Promise of Breast Cancer Research  

Few have a more significant history or deeper relationship with breast cancer research and researchers than Dr. Larry Norton. Dr. Norton is Scientific Director of the Breast Cancer Research Foundation. He is also one of the organization’s founders. Dr. Norton serves as Medical Director of the Evelyn H. Lauder Breast Center at the Memorial Sloan Kettering Cancer Center, and among many other honors and appointments, he was a U.S. Presidential appointee to the National Cancer Advisory Board – the board of directors of the National Cancer Institute.

 

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Read the transcript of the conversation below: 

Chris Riback: I wanted to start with you really at the highest level, which is why research? At some point in your life, you decided on medicine and science for your career and there are obviously many directions that choice can lead. What was it about the research side that said to you, "This is where I can make a real difference?"

Dr. Norton: Actually, I remember the exact moment. I was in college and several of us were interested in work in health and trying to improve the health of the public. Got into a little bit of a debate, and the question that was asked of us was, "If you took care of somebody using all the medical knowledge that currently exists in the world and made absolutely no mistakes, and applied all the right treatments, and that patient still didn't do well, how would you feel?" Some of my colleagues said, "Well, I would feel okay because I know that I did the very best I could and I applied the very best knowledge and I did it in the most compassionate, possible way and if the patient didn't do well it's because of the limitation of knowledge, but I had done my job as well as I could."

I said, "I'd feel terrible about that," because I think my job should be not only to apply the highest level of knowledge in the world, but also to improve that because if a patient's not doing well, that means there's something we don't know, and if there's something we don't know, my job is to try to find those things out and not just apply the very best knowledge if it's not going to lead to a good result. It was a very clear that I had already made the decision that I didn't even know that I had made the decision to follow a research career. I'm also a clinician, I also take care of patients and have taught many people how to take care of patients over the years, and have lectured about the standards of care, particularly in the area of breast cancer for many decades, but I don't see my job as just delivering the best care. I see my job as constantly improving the state of care so that we can do better and better.

Chris Riback: It almost sounds like a continual sense of curiosity is part of what drives an interest in research. Am I hearing you correctly?

Dr. Norton: Yeah, but it's not just curiosity. All scientists are curious all the time. It's not just that. It's trying to make a concrete difference in the way patients are treated. I know that I will never be comfortable until breast cancer is eliminated from this earth and people have said to me, "What happens when that happens? Because that's what you've dedicated your life." I say, "I'll probably take a week or 2 off and do some skiing, spend some time with my family, and then I start to try and cure something else." Many of us in my field are driven to constantly improve the state of the art and so it's not just a curiosity. It's also a desire to do good in the world, a desire to help people and to save people. That's a very, very strong motivation.

Chris Riback: On that front, number of areas where you have been either created yourself or obviously as part of teams and incredible research and outcomes, one of them and I guess most recently, you'll correct me if I'm wrong, but much of your research or some of your research at least has focused on immunotherapy. Could you give a brief explanation of it? Description of it? Maybe, in terms of breast cancer, why has immunotherapy reemerged as a potential strategy for breast cancer treatment?

Dr. Norton: Well, I mean, it's a very, very interesting topic, and I've been involved in a lot of areas of research. Currently, immunotherapy of cancer is one of those areas that we feel very, very passionate about, but I feel passionate about all of the areas. In fact, people constantly ask me, "Where is the breakthrough going to happen?" I say, "I will answer that if you tell me what's the most important part of the airplane? Is it the left wing? Is it the right wing? Are the wheels? The steering mechanism? What's the most important part?," because you can't answer that. The most important part is the whole airplane works. If any one part of it doesn't work, you're going to be in serious trouble.

It's the same thing with medical research. There has to be a lot of research in a lot of different areas, and they all have to work together and integrate together. That's one of the things that makes the Breast Cancer Research Foundation so terrific, is that we cover a very broad spectrum of topics in cancer medicine, with a focus on breast cancer but not just breast cancer, because all cancers are really related. If you solved a problem in 1 cancer, it's going to relate to other cancers as well. In my role in the Breast Cancer Research Foundation I see myself involved in essentially every project. I interact with the investigators in almost every project at some point during the year, some more than others.

My strongest area of involvement directly is with colleagues who are studying 2 parts of the problem and that's how do we get the immune system to help us eliminate all the cancer cells? The other is, why do some cancer drugs work for a while and then cells become resistant to them? These 2 areas are actually rather related because they all involve the thing that makes the cancer cancerous which is abnormality in the cancer's DNA. In the immunotherapy area, those abnormalities in DNA produce abnormal proteins that the body, in fact, can recognize as being abnormal. Just like when you get an infection, let's say with a bacterium, your body says, "Hey, the proteins in that bacterium are not part of my normal body, so I better develop means of eradicating it."

That's what your immune system is really for. Your immune system was developed to attack foreign invaders in the form of bacteria and viruses. The problem in cancer is that the proteins are either not abnormal enough, or that those proteins are not being released so the immune system can recognize them, or they're also being released with normal proteins and other normal molecules that the body says, "Hey, that cell is abnormal but it's still my cell, still the cell for my body, and so I better not destroy that." We have checkpoints, and those checkpoints stop the immune system from attacking our own cells. The big breakthrough has been the discovery that what those checkpoints are and how we can inhibit them, so that we can then unleash the ability of the immune system to attack the cancer cells.

That work has really opened up immunotherapy for cancer in a dramatically effective way and at very, very exciting times. We are studying vaccines that can turn on the ability of white cells which the white cells are the effector cells of the immune system, turn on the white cells to attack the cancer cells, ways of turning it on in conjunction with ways of inhibiting the checkpoints. We're studying ways of releasing those abnormal proteins in large numbers so that the immune system knows that those abnormalities are present, such as by freezing cancer cells in the body and then when those cancer cells thaw, they can release signals to the immune system so the immune system can work. Then, in conjunction with inhibitors of those checkpoints, the immune system can do their job.

We're also studying how we can attack those abnormal components, those products of abnormal DNA directly, and how cells can develop resistance when we attack them by developing new abnormalities in DNA and new abnormalities in the signaling of the cancer cells. It's a very different world of cancer medicine than it was just a short time ago because we now have the tools of looking at DNA, looking at the proteins and other molecules that the cells make in response to the abnormalities in DNA, and we also have tools to be able to attack those abnormalities, both immune therapies and drug therapies.

Those are some of the things that are some of the most exciting things we're doing now in cancer medicine. This relates directly to breast cancer, but it also relates to all cancers. As I said, if we solve the problem in 1 cancer, it's going to open up the opportunity to solve the problem in many other cancers.

Chris Riback: In listening to you, it sounds like so much about the research, at least for a lay person in listening to this, is how connective it is and how connected it is. It sounds like, for example, the research that you've done historically on DNA is now very much part of what you're talking about in terms of any of the current research on immunotherapy and I assume that that's part of the network and from a BCRF point of view, part of what BCRF supports in terms of the various types of research and in some ways, that research must end up connecting or being connected both throughout one's own life, in your own life, but also from research team to research team. Is that part of it or is that ...

Dr. Norton: Oh, that's a very big part of it. I think you hit on something really important and really special about the BCRF. Remember the Breast Cancer Research Foundation was founded around Evelyn Lauder's kitchen table, where she and I were in a conversation that Leonard Lauder, her husband, later joined about how we can really make a difference against cancer, what's the best way of supporting cancer research. We knew that there were great researchers in the laboratory, we knew that there were great researchers in the clinic, as well as great physicians took care of patients and we recognized that indeed just what you're saying, some of the connections between laboratory investigators and clinical investigators, those connections were really not very strong in those days.

She was just commenting about her own experiences with creative work, and the kind of field that she was in with cosmetics and other things related to beauty, as well as her own work as a photographer, it was all about connections. She said, "What's really necessary is to have very creative people and give them security that they can try out innovative things and the freedom to explore things as those things became obviously to them that they merited exploration," but also the connections between things that you don't normally see connected. Creativity is really very much about connecting ideas from 2 different places that people in those 2 different places wouldn't necessarily recognize are connected.

We needed some way of putting together scientists, clinicians, investigators of all sort in an academy where they could do their own work, but they could also be connected to other people and they would have the freedom to pursue their ideas as well as the security of knowing that if those ideas didn't pan out that it was a good idea and it was tested properly, they would be rewarded by continued support of their work going off into the future. That's the reason why we've been able to accomplish so much, I think, over the years, is because of those fundamental ideas. We have people studying tumor biology, we've got people studying how you can inherit abnormal genes, DNA from your mother or your father that can predispose for cancer, things you can do in your lifestyle such as exercise and weight control, and many other aspects of lifestyle that affect cancer.

Obviously a strong interest in cancer treatment, a strong interest in quality of life after you've been treated for cancer and fundamental understanding of the way cancer cells spread. The big problem with cancer is not the growth in the organ that it comes from, let's say the breast, but the fact that the cells could spread to other parts of the body. We call those metastases. For that reason, we launched an independent program in BCRF involving roughly 3 million dollars committed to an international understanding of why cancers spread by studying the DNA in the cancer cells. This is a huge international project, a multi year project to define all those abnormalities but this is being connected to understanding fundamentals of what those abnormal molecules do, what the abnormal DNA signals the cells to do, how some people predispose to cancer and everything else that I mentioned all together.

The reason is because we want to support everybody working together in a way that they can grow from each other's ideas, but always with a focus on the problem which is we've got to get rid of cancer. We've got to prevent it if we can, we've got to treat it if we can, prevent it. We've got to find out what causes it in a much more sophisticated way so we can develop better interventions for both prevention, lifestyle changes, as well as treatment and minimize the impacts of treatment on survivorship thereafter and this has been accomplished. I mean, the excitement of our meetings is quite extraordinary.

Not just because of specific things that we're discovering which we talk about and we present, but the exciting ideas that arise when people in different fields say, "Hey, I know something about that. I didn't know that it was connected. Let's work together and let's see if we can pursue that idea." That creative spark is fantastic and I think has led to significant advances and moved us ever closer to the ultimate goal which is ridding this world of cancer.

Chris Riback: You know, that reminds me one of the things in preparing for this conversation, I read where you once said, "Great science is a creative art," and I read that and I just stopped and thought to myself, "You don't hear that very often. You don't hear the connections and the creativity behind science. You don't hear that connected to the creativity behind art." Is that what, in a sense, you ultimately hope that you're supporting and that you're doing both great science but also creative art?

Dr. Norton: Yeah. Creativity is creativity, in any field. I mean, in art, in music, in theater, in writing, and science is not that different, that great ideas occur because there's a spark or there's usually a connection between 2 things that people didn't see before. If you look at the history of science and you look at the history of art, if you go back and say, "A century ago, 2 centuries ago, 3 centuries ago," you'll see that artists and scientists were basically trying to solve the same problem and often didn't realize at the time, but was pretty obvious in retrospect, that they were thinking about the same kinds of things.

I think that talking to a lot of artists and people who write about art and write about contemporary culture and scientists who are studying the cancer problem, I think we're talking about something very similar which is identity. How does the cancer cell see itself? How does it see its relationship to the cells around it? How do people see themselves and how do they define themselves? Can you have multiple definitions of the same individual? Of course you can. Can the cell be a health cell and an abnormal cell at the same time? Of course it can. I think some of the same issues that we're trying to solve in the arts we're trying to solve in the sciences, and I think that we're hoping there'll be more of an interchange, in fact, between the arts and the sciences because we can learn from each other in that way.

Chris Riback: On another item that you said, that you talked about, the quality of life. Whenever I talk with scientists about medical research and breast cancer, but other types of medical research as well, I'm always struck by the balance between prevention and treatment. I mean, obviously both are of prime importance and I guess it all comes down, and you can tell me if you agree, to quality of life. How do you balance that energy and focus between prevention and treatment?

Dr. Norton: Well, again, what's the most important part of the airplane? The fact is that it's all important. You prevent everything you can, but you often can't prevent everything. We know so much about infectious diseases, for example. We know about viruses, we know bacteria. Hand washing and sanitation was the biggest advance against infectious diseases and that was a huge advance and even though people know about hand washing and we have good practices in terms of preventing spread from one person to the other, people still get diseases and have to be treated. We still need antibiotics. Even infectious diseases where we know a lot about prevention, where we have vaccines and we have means of spreading the transmission of viruses and bacteria, still, people will get sick and will need antibiotics. You need both prevention and treatment together. It's not one or the other.

The left wing and the right wing of the airplane are very important for the airplane to fly. You need them both. What's really intriguing is, however, that often the same intervention that has therapeutic effects, in other words, that you can use to treat a disease, those same interventions can be modified to be used to prevent a disease. A very good example is the use of the drug, for instance, this is a good example, is Tamoxifen. Tamoxifen is used to treat advanced breast cancer because it stops the estrogen receptor from working and a lot of cancer cells need estrogen to live. You could also use that drug to prevent breast cancer and we do that and we apply that particularly in patients that have had one cancer to prevent another cancer from occurring.

Understanding the fundamental biology of the process, in this case, the fundamental biology of the estrogen receptor, and by the way, we have fantastic scientists who are teaching us more and more everyday about the way hormones and cancer relate to each other, but understanding that fundamental biology will lead to not only a treatment for a cancer, but also a prevention strategy. I think that we're going to be seeing this more and more as we understand biology better and better.

Chris Riback: Just to close out, Dr. Norton, I'm struck by you painted this picture of sitting around the breakfast table with the Lauders so many years ago, I guess back at least, BCRF was founded in 1993 so obviously some time before that. Is the reality today and the scientists that you funded and the connections that are occurring, was this the vision? Is the reality today what you see? Do you look back and think, "Yep, this is the vision that we had and the hope. We didn't know that we'd get there, but this is the vision," or did it evolve differently than you might have expected it to?

Dr. Norton: Well, it's a little of both, that it is certainly in terms of the size and the quality and the energy of the organization, it clearly exceeded our dreams back in those days. We're the largest non-governmental funder of breast cancer research in the country at the present time. A very high percentage of the really high quality scientists, I wish we could have them all involved in our organization, but a very high percentage of them are involved in the organization across the board, in many, many different areas, but I'm not going to be happy and our scientists and doctors and other investigators are not going to be happy until we've eradicated all of breast cancer and then other cancers, and we're not there yet.

However, we have made great strides and more people being cured today than ever before. More cancers being prevented than ever before because of what we've learned in many different areas. One of the key areas that we've been involved with since essentially the beginning is this notion that you can inherit a susceptibility to cancer, and now we can actually look at your DNA and tell you if you inherited a very high sensitivity to developing breast cancer and ovarian cancer and there are interventions that can make a real difference, that can dramatically lower your chances of getting breast cancer and of getting and dying of ovarian cancer. That's something that's happened during the lifetime of the Breast Cancer Research Foundation.

We've made huge advances in treatment, in particularly in what we call "adjuvant therapy" where applying treatments at the time that the patient has their first breast cancer in the breast, we can dramatically lower the chances that those cancer cells will spread to another part of the body, but we've also made improvements in treating patients with metastases where if it has spread, we can control the cancer for longer than ever before, and also do that with a very, very high quality of life. We've seen a lot happen in the time that the Breast Cancer Research Foundation has been functioning.

That's important, but what's really important is that we now have new tools, we have new approaches, terrific dedicated scientists, and if we all continue to do what we're doing which is work together in a non-competitive way, help each other, share our best ideas, have the freedom and security to really be creative with our ideas and then apply them well into the clinic, we have ... We're one of the supporters is something called the Translational Breast Cancer Research Consortium which is a large number of the best cancer centers doing cancer research in the country, doing clinical trials of our ideas, and translating them into clinical trials so that patients can benefit and we can learn more so we can help more patients.

The machinery is there and we have to understand that that's the way we're going to rid the world of cancer, by doing high quality research across the board, at many different areas, working together, translating those ideas so that we can actually look at them in the clinic, see if they work, improve them, and help develop ways that we can translate this into general practice as well. The machine is there, the machine is working, and now we just have to keep dedicated and finish the job.

Chris Riback: Dr. Larry Norton, a founder of the Breast Cancer Research Foundation, the BCRF Scientific Director, Medical Director of the Evelyn H. Lauder Breast Center at the Memorial Sloan Kettering Cancer Center and numerous honors and appointments throughout your career. Thank you very, very much for your time. I'm Chris Riback. This is BCRF Conversations. To learn more about breast cancer research or to subscribe to our podcast, go to BCRFCure.org/podcasts.

 

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