Shelley Hwang is a Professor of Surgery and Chief of Breast Surgery at Duke University in Durham, North Carolina.
Shelley Hwang: I have several roles in the PS-OC. I’ve been involved since its inception about four years ago and I collaborate in two PS-OCs. There’s one that’s organized through the Bay area, and that one is led by Jan Liphardt and Valerie Weaver, and through that group I look at the environmental factors around tumors that can lead to cancer progression and cancer initiation. And then through a separate group which is located in Southern California in the Scripps Research Institute, the PI there is Peter Kuhn, I’m helping to look at the role of circulating tumor cells in dissemination of cancer.
Pauline Davies: And does any of the work you’re doing with the PS-OC inform your clinical practice?
Shelley Hwang: You know that’s a really excellent question and I think one of the charges of the PS-OC is to have new ways of thinking about this whole problem of cancer. We haven’t gotten to the point where we’re actually starting to implement some of our ideas into clinical practice. But I can tell you on a daily basis, when I go to clinic and I have a patient sitting across from me, a lot of the concepts we’re discussing here in terms of treatment resistance and the role of the tumor micro-environment, they are things that I actually can start thinking about, if not actually incorporating into practice on a daily basis.
Pauline Davies: So when your make treatment decisions are you making decisions based on the stuff you learned in medical school or are your ideas evolving?
Shelley Hwang: You know one of the really fantastic things about my job and why I find it so exciting is that you’re never done learning, and I think one of the great things that’s come out of the PS-OC is that I’ve just developed a greater appreciation for how even our basic concepts of what cancer is and what causes cancer to progress and metastasize, none of these concepts are stuck in stone. So its very fluid and I think there’s great opportunity to understand, or to think about cancer in many different ways. So an example of that will be; the historical way of thinking about cancer is that it is a cell that’s gone amok and it has all these genetic changes and because of that, it behaves badly and eventually takes over the host. But I think one of the really interesting new thoughts that are emerging from the PS-OC, and one that fortunately I’ve been involved in helping to push forward, is that it’s interaction between the cell and the host, or between the tumor and the environment that it finds itself in that helps to determine the fate of the interaction of the cells. So I think understanding a little bit more about the role of the surrounding cells that are in the environment of the cancer and how to control those cells in terms of modulating the tumor behavior is one area that is really fascinating and it really helps me to think of patients in a completely different way. I think the way that we risk-stratify patients is likely to change. I think the way we think about treating patients with very early stage cancer versus those with very advanced stage cancer, all of these things are being turned on its head and I think that’s really an exciting aspect of being involved in this work.
Pauline Davies: And what’s the most exciting idea that you’ve heard so far in this conference? What’s the one that most appeals to you?
Shelley Hwang: So we heard a really excellent talk today. And this wasn’t a new concept to me but it was a different illustration of understating how tumor cells can develop treatment resistance. So, in a nutshell, the speaker was talking about how different evolutionary forces can converge on a heterogeneous population of cells to be able to separate cells into treatment sensitive and treatment resistant clones. And this whole concept of being able to modulate the activation energy that’s required for a cancer cell to become either treatment sensitive or resistant is a really new way of thinking about how to treat cancer. So, rather than impacting the tumor cells themselves, what you want to do is modulate the environment and the ability of cancers to develop different phenotypes, rather than attacking the phenotype itself. And I think these are the kinds of really exciting and very unique ways of thinking about the interaction of cancer cells and the patient. And ultimately we’re here to make an impact in cancer care. And when I take these ideas back home, I think it starts fostering new ideas about how to design clinical trials, how to start thinking about giving chemotherapy in different sorts of ways, whether to give it more frequently in small doses versus less frequently in larger doses and how everything we do can impact the ultimate behavior of cancer cells and hopefully help extend the survival of patients who have cancer.
Pauline Davies: And turning to your own field, breast cancer, are there any new treatments coming along that will be beneficial to patients?
Shelley Hwang: So my particular area of interest is in DCIS, which is the earliest detectable form of a malignant change, and I think a lot of these concepts that we’re discussing today in terms of the interaction of the tumor cell and its environment, the ability to contain the behavior of cancer cells so that we don’t focus all our energies into killing the cancer cells themselves, but thinking about the larger system in terms of containment of tumor, containment of tumor progression. Those are the things that are very exciting and I can take those home with me and help to design clinical trials with those kinds of new ideas.
Pauline Davies: And there’s been a mention about breast density in this meeting and breast density, dense breasts actually predict that disease gets pretty nasty. What can we do about that?
Shelley Hwang: So breast density is one area of active research that I think has been fascinating but we really haven’t made that much in-road into. So apart from a genetic mutation like a BRCA mutation, breast density is one of the strongest risk factors that a woman can have for development of breast cancer. And many states have now mandated, in the last 12 months even, that a woman be given information about her breast density in addition to her mammogram results. But of course it’s really hard to know what a woman is supposed to do with that information. So there are now emerging a group of clinical trials, and I can describe a few of them in just a moment, that look to see if breast density can be a surrogate biomarker for response to a chemo-preventive agent. So an example of that would be; a woman who is at high risk for breast cancer and who’s treated with tamoxifen for five years, some of these studies have demonstrated that if a woman has a reduction in breast density with a chemo-preventive agent, then that can actually be translate long-term into a reduced overall risk of breast cancer. The reason that’s important is because that will really significantly shorten the time interval to get a meaningful result. You don’t have to wait until the woman gets breast cancer to know that your chemo-preventive agent is working. You can just determine what impact the chemo-preventive agent has on the breast density itself. So there’s another group of studies where we’re looking, in a cooperative group trial, to see if a diabetic agent called metformin is able to reduce breast density and so we’ll have results from that in a few years. And I think these are the kinds of studies that need to be done with surrogate end-points so that we don’t have to wait until a person gets the event to know whether what we’re doing in a preventive setting is actually effective or not.
Pauline Davies: And why is increased breast density so dangerous?
Shelley Hwang: My collaborators and I like to think about the whole breast tissue as exciting not in a vacuum but it’s a packaged organ. It’s full of scaffolding, collagen, lots of other cells that comprise the tumor environment and I think it’s the combination of all of those things that lead to a fertile soil for cancer to grow or a resistant soil where cancers are less likely to grow. So it turns out that if you can measure tissue stiffness, the amount of stiffness in the breast environment can actually determine not only whether you get cancer, but the kind of cancer you’re likely to get and I think we’re now starting to unravel some of the molecular mechanisms that help to explain that.
Pauline Davies: It’s been a very exciting meeting, hasn’t it; lots of controversy so, can you highlight any of that for me?
Shelley Hwang: Well, one exciting new concept that was highly controversial was this concept that was put forth of thinking about cancer cell populations as a different species from the host in which it arises. So to look at the phylogenetic tree and to think about cancer cells as being a branch on the evolutionary tree that’s distinct and different from the branch that the host is on. So, I think that was kind of a mind blowing thought. I never imagined cancer cells, which reside in a host can actually be thought of to be a completely separate species! So that was kind of interesting. It was something that I hadn’t been exposed to before but I think that’s the value of the PS-OC. You bring all these sometimes crazy ideas and over time, with the proper data, I think we can start to define whether these things actually make sense. And I think with these brand new ideas, if the data supports it, I think it gives us a completely different framework in which to think about cancer treatment.
Pauline Davies: So you’ve enjoyed the meeting?
Shelley Hwang: Oh, I always do. It’s really a privilege to be involved with so many people who are so smart and brilliant and who have really exciting new ideas to bring to the table.