October 17, 2018

Premier cancer researcher cites successes and sees hope

This story originally appeared on themedialine.org.

Dr. Larry Norton is the Deputy Physician-in-Chief of Memorial Sloane Kettering Cancer Center in New York and hailed by many as one of the foremost cancer researchers in the United States.

Dr. Norton was in Israel for a conference hosted by Soroka Medical Center in Be’er Sheva, highlighting the new frontiers in cancer research.

Dr. Norton was interviewed by The Media Line’s Felice Friedson.

TML:  Dr. Norton, why Soroka Medical Center?

Dr. Norton:  Soroka [Medical Center] is a wonderful place to do the kind of research that we have to do. It is, first of all, populated by wonderful doctors and scientists; and in addition to that, the Negev [the southern desert region of Israel] has 1.1 million people and they’re all served by that one hospital. In addition to that, the hospital has immaculate electronic medical records. So, we started the project there several years ago looking at the relationship between bone health — that’s osteoporosis or the opposite, which is bone density — and breast cancer. It’s a very diverse population and they all go to Soroka for healthcare and they all have great records.

I learned something else when I was [in Be’er Sheva], which is that there is a pioneering spirit in that part of the world, where people have a lot of confidence in the future. They have a confidence in themselves and they are willing to try new things and they’re willing to try exciting things, and that sense of confidence and doing things that are new and unconventional is very important for research.


TML:  In what year did you begin this collaboration?

Dr. Norton: Well, it’s about two-and-a-half years ago. We’ve already discovered something really important that we can’t explain and of course, great science always happens when you can’t explain something.  If you have breast cancer, your bones are more brittle than people without breast cancer, but it’s not osteoporosis necessarily. Of course, osteoporosis makes it more likely that you’ll get a fracture, but people with breast cancer seem to get fractures at a level of bone strength that is higher than the level at which you would expect people to get those fractures. So something about the breast cancer is making the bones weak, and that tells us that there is signaling between the bones and the cancer:  that’s a very important clue for what makes cancers cancerous. It’s a whole new definition of cancer.


TML:  How do you go about trying to define how that works within the framework of cancerous cell research?

Dr. Norton:  That’s what’s wonderful about Soroka. These patients are all being followed, taken care of by excellent physicians; we’re going to look at their blood to see what some of the factors that are involved are. We’ll also examine their tumors — everybody has been diagnosed with breast cancer so there’s a tumor sample that’s available. Of course, all of this will be done very carefully and very ethically, but our intention is to do the best studies we can to try to figure out the connection between bone health and breast health. And we intend to explore other areas as well, for example, the terrible impact of obesity on breast cancer. And it’s not just the fat that’s in the breast tissue, it’s actually fat anywhere in the body. We’ve learned that fat can actually teach white blood cells to support the growth of cancer. A certain kind of white cell can be stimulated by fat tissue to actually promote the growth of tumors:  it’s another reason not to be obese.


TML:  So much has changed in cancer research during the last decades, so what can you point to that’s different today?

Dr. Norton:  The main thing is the availability of tools that we can use to really examine the molecules that make the cancer cancerous. It used to be that we would study one molecule at a time; now we can study thousands of molecules at the same time and use very sophisticated computer tools and computer modeling to see the way they all inter-react. We’re getting down to the very fundamental understanding of what life is all about at the level of molecules. Never before in the history of the world have we had that capability.


TML: Your research concerns the basic biology of cancer, tumor causation, and growth, with an emphasis on the approach to improving diagnosis, prevention, and drug treatment. You co-conceived the self-seeding theory that alters the way we look at breast cancer. Can you explain this in layman’s terms?

Dr. Norton:  Yes, this was actually the first lecture done by my colleague Elizabeth Comen. We have discovered that when you have a breast cancer some of the cells can go loose into the blood stream and we all know that those are dangerous cells because they are capable of going to other parts of the body, such as if they start in the breast where the original breast tumor is, they can travel to the lungs or the bone or the liver and can cause trouble there. In fact, most people who die of cancer die not from the disease where it started but from where the cells spread. But we discovered that cells can leave the primary tumor and come back to it. Also, cells can go from one metastatic site: in other words, if it’s in the liver, it could leave the liver and go to the bone or go from the bone to the lung and cells can move around. This has totally transformed our notion of what cancer is. We’ve always thought of it as cells dividing and piling up and building up, but now we know they also move around, and so one very important feature of this is that we can start to develop drugs that stop them from moving. Also, when the cells move, wherever they go they attract white blood cells and blood vessel cells and the blood vessel cells and the white blood cells all come from the bone marrow and they go to the place where the cancer is, and help it grow. And that’s enabling us to develop approaches to cancer that treat the white blood cells and the blood vessels and not just the cancer cells. You know, nobody ever died of cancer cells. Cancer cells themselves are harmless — they’re only harmful if they form tumors and masses. And those tumors are actually cancer cells and white cells and blood vessel cells and other kinds of cells and we’re learning how all of that works together and its giving us great insight in how to prevent the disease and treating it.


TML:  Dr. Norton, this begs the question, why aren’t physicians looking at the body as a whole rather than at isolated areas like the breasts?

Dr. Norton:  Well, the research is hard and I think doctors are looking at the body as a whole now and I think that’s one of the great revolutions that is happening in contemporary medical science. It’s not just about the cells themselves, it’s also about how they connect to each other. It’s all about communication, and that community of cells is really where the action is, and we’re learning that.

It also tells us important things about what we can do to stay healthy. If, indeed, fat tissue can teach white blood cells to support the growth of cancer cells, that’s another reason not to be obese and exercise is a not only a good way to control your weight but it strengthens your bones and having healthy bones may be a very important thing as well we’re discovering. So, the whole body works together as a unit.


TML:  Well, to what end? How can a physician understand an individual’s bone metabolism as a preventative measure?

Dr. Norton:  Well, we study the bones and we study the cancer and we study the white cells and we study the blood vessel cells and all the other components, and then putting it all together in one package — that’s where the challenge is and that’s why the huge advances in computer science is so important because computers can calculate millions and millions of possibilities in a fraction of a second and we can simulate all sorts of different relationships and see which ones actually match the reality. We could never do this before.


TML:   There are varying opinions on the frequency in which woman should have mammograms or CT scans and what age they should begin. What does research tell us?

Dr. Norton:  Well, mammography is still the very best way we have of diagnosing cancer when it’s tiny. And we know for sure, in breast cancer, diagnosing it when it’s small is very very important. In the United States, our recommendation is very firm that women should get an annual mammogram starting at age 40 — that’s for an average risk woman. If you’re at higher risk, you might want to start earlier, depending upon individual factors. I know that in Israel the more usual thing is to start annual mammograms at age 50, and again, that’s a local decision I’m not going to challenge. But probably somewhere between 40 and 50 is the right place to start it.

One of the exciting topics that we’re talking about is trying to individualize screening, so we call it risk-adjusted screening, for some women, starting at age 25 might be the right thing; for other women they may not need it at all, and so classifying the risks for the individual and putting them into an individualized screening program is something that we’re working hard to accomplish and I think that’s going to be a big advance.


TML:  How would you determine that a woman does not need it at all?

Dr. Norton:  Well mostly by analyzing her genes. You know, you can inherit a bad gene from your mother or your father and if you do that your risks of breast cancer are huge. So for that individual, if they choose screening, they should really start very young, probably at age 25. We also add other things such as MRIs for the breasts to get a better handle on their early diagnosis, so that’s a very high risk situation. We haven’t yet identified a group of people who have such a low risk that they don’t have to be screened at all but that’s one of our goals. Because of your genetic makeup and lifestyle issues and past medical history you may fall into a situation where your risks are low enough that screening doesn’t make sense. We haven’t found that yet, so we’re still recommending for women to have annual screening.


TML:  The big question on many people’s minds is what causes cancer? In the case of women, does hormone therapy expose women to cancer?

Dr. Norton:  Now most cancers are probably caused for reasons that we don’t understand and there may not actually be any cause, per se. What’s the cause, for example, of aging? There is no cause of aging: it’s just something that happens as time passes for a human body. And similarly, cancer may be one of those things that isn’t actually caused by any abnormality in the environment or anything the person does wrong, but some women are at higher risk than others. One thing you can do to put yourself at high risk is to take estrogen and progesterone in your post-menopausal years. This has clearly been proven by careful research that it very significantly increases your risk of getting breast cancer so that is not something that I recommend.


TML:   What are the current statistics, the data of women who are getting breast cancer in the US and in the world; and the survival ratio?

Dr. Norton:  Well, that depends on so many factors it’s almost impossible to say in a simple sentence. It depends upon your own family history, it depends upon your environment, and as I said it depends on such things like obesity and hormone use. It can be said that if you live to a ripe old age in the United States, your chances of not getting breast cancer are in the range of about eight out of nine, which means one in nine will get breast cancer at some time in their life and that’s a fair statistic. That’s of course a lot of women and therefore it’s really imperative that we get better at diagnosing and treating the disease to save more and more lives.


TML:  You developed and identified an approach to therapy called dose density, which maximizes the killing of cancer cells when minimizing toxicity. How has this been implemented?

Dr. Norton:  Well, this is actually a well-established approach. With my colleague, Richard Simon, at the National Cancer Institute in Bethesda, Maryland, we confirmed that cancers grow by a pattern of growth that is fast at the beginning and slows down as the tumor gets bigger. When we saw that pattern of growth we realized that one of the big problems with killing cancer cells was if you let too much time pass between your doses of therapy, the cancer could grow back very quickly. So, the hypothesis was that getting in a reasonable dose of drug very often was better than getting in a very high dose less often. In fact, 10% more patients were cured of cancer by just giving the drugs every two weeks instead of three weeks. So it’s become standard to use that in the treatment of breast cancer right now, and many many patients in the United States and throughout the world are getting dosed-in therapy, it shows that not only good science but good mathematical science can have a huge impact on our ability to cure cancer.


TML:  Dr. Norton, you’re the principal investigator of a program through the National Cancer Institute whose aim is to bring breast cancer laboratory advances into clinical practice. What’s the forecast for breast cancer research in 2025?

Dr. Norton:  Well, we need to make sure that the funding stays intact – national cancer state funding, philanthropic funding, and all the sources. The amount that’s spent on research required is actually very very tiny considering the magnitude of the problem. So that’s something I just want to emphasize: it’s very very important to continue the research and to keep it very robust.


TML:  Dr. Larry Norton,  one of America’s – and the world’s — foremost cancer researchers,  thank you very much for your time and for your important work.