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Investigating Breast Cancer: Shelley Hwang

Read the full transcript of the latest episode of BCRF’s official podcast hosted by Chris Riback and featuring Dr. Shelley Hwang

Chris Riback: Dr. Hwang, thank you for joining me. I appreciate your time.

Dr. Shelley Hwang: Really nice to be here with you today. Chris,

Chris Riback: Before we get into your current work and in particular your COMET study, I have to start with a scene in a video on you that I saw, and in this video, the narrator is describing how you are an internationally renowned surgeon, scientist and leader in the field of breast cancer oncology. It’s serious and impressive stuff. While those words are being spoken, the patient is on the operating table as a nurse is inserting the IV, and you are there ready to perform surgery and you are looking directly into the patient’s eyes and holding her hand gently, caressing no words. You are this world-renowned scientist, simply telling another human being who’s surely scared. Don’t worry, I’m with you. I think my question is obvious. Who are you? It was an extraordinary video and just a scene that I anticipate provided a window into the question that I asked.

Dr. Shelley Hwang: Well, Chris, of all the titles you just gave me, I would say that the real me is the one who is looking at the patient and trying to make them feel less anxious about her surgery. I did not go into this field to do research. I really wanted to be a surgeon to help patients. And I know that sounds very trite, but I think that’s really what motivates most doctors to do what they do. And I think it’s really through understanding that patients’ perspective, that I got really interested in trying to focus on ways that I could make the experience less frightening for all the many patients I would never get to meet.

Chris Riback: It’s understandable, I believe you, that that was a motivating and remains a motivating factor. Among the things that struck me of course, is that with any professional, maybe even I think about an athlete or a ballplayer maybe to get into it at the beginning for the love of the game or some such thing, to maintain that core sentiment in any profession for a career such as what you’ve had and have that be so evident that struck me as well.

Dr. Shelley Hwang: In Malcolm Gladwell’s book Outliers he talks about how it takes 10,000 hours to perfect a craft or something that you do in your everyday work and really get it to a level where there’s flow and you don’t have to really think about what you’re doing anymore. And so I think with being a doctor, it’s particularly rewarding when you get to that place and you’re not thinking about the details of what you’re doing technically. It just kind of flows. And what that does is it allows you to think about, think more about the individual and the patient and the person. And I think this is one gift that’s come out of doing this for a long time now, is that I started off in the humanities when I was an undergraduate and took this very long detour through science and medicine and chemistry and all the things that you need to learn to be a good physician.

But I feel that now in the fullness of time, it’s gotten back to where I’m centered again in the humanities and research and science is all just exciting and wonderful, and we’ll talk more about that. But really at the end of the day, it’s the difference that you can make in patients’ lives. That is the motivating force, both to keep me engaged in what I do as a physician, but also to come up with the best research question. So my best ideas always come from my patients who are just asking, why does it have to be this way? Or why don’t you do it like this? It’s that fresh perspective that patients bring that makes us, I think if we’re open to it, reassess how we could be doing what we’re doing even better. When I’m with the patient, there’s no one more important in that room than the patient. We have to be addressing what the patient needs and not what my agenda is or what the medical system’s agenda is. It’s really what the patient needs for their life to get over what’s happening with them.

Chris Riback: Amen to that. Talk to me if you would please about ductal carcinoma in situ too. I will say, I know you do it all the time explaining exactly what it is. I was shocked, and maybe it’s because I don’t know enough, you can explain please. For me, it’s diagnosed in more than 60,000 women each year in the US alone. So what is it? And that feels like a really big number to me.

Dr. Shelley Hwang: It actually is a pretty big number, and it’s especially astonishing when you think that before mammograms, that number was probably just in the thousands because most DCIS is diagnosed when women go for a mammogram because everybody tells them that they should, and I believe that they should as well. But nobody ever tells them what the downside could potentially be of getting a mammogram. And one of the downsides is that you get diagnosed with this very, very early condition. Some people disagree with me, but I think it’s pre-cancer, not a cancer yet, and not really understand. They feel well, they don’t have any symptoms, and all of a sudden somebody tells them that they have a cancer and they need to have surgery to take it out. And a lot of times it’s a mastectomy.

Chris Riback: Describe exactly what it is. The tumor’s in the milk ducts. Is that correct?

Dr. Shelley Hwang:

Yes. So in answer to your question about what DCIS actually is, there are two main types of cells in the breast. One is in the lobules, which makes the milk, and the other cell type is the ductal cells that transport the milk out of the lobules. The ductal cells are usually confined to a long tube, the duct, but when cancer develops, these ductal cells can break out of the ducts and invade into the surrounding breast tissue. And when we see that onto a microscope, we call that invasive cancer. A lot of times these cells start looking abnormal, even highly abnormal, but they don’t go beyond the confines of the duct. And that’s the diagnosis that we call ductal carcinoma in situ.

Dr. Shelley Hwang: Back in the day, we always used to think that DCIS would turn into cancer. So even if it was confined to the duct, we had to do something about it and it was an emergency and we’d have to take the patient to the operating room. A lot of what we’ve learned in the last 10 or 15 years is that there are many, many different kinds of ductal carcinoma in situ, including some DCIS that just stay within the ducts quite comfortably for the rest of the patient’s lives. And what we really need to move towards is a better understanding of what DCIS will have a greater likelihood of invading out into the breast tissue and becoming invasive cancer, and which DCIS is really going to stay confined to the ducts, in which case it’s a completely harmless condition.

Chris Riback: And as an outsider, one can understand that tension between yes, wanting people, women to be aware and maybe even on some level on alert that may not be the right phrasing exactly, but aware and yet at the same time, not panicked, not put into such levels of concern that that somehow becomes either overwhelming or moves one off of one’s natural path. Am I characterizing that tension correctly?

Dr. Shelley Hwang: I think it’s even more than that. I mean, I think it’s real fear, and I think anytime a woman has something abnormal on a mammogram, I mean, forget about finding something. Anytime a woman goes for a mammogram, I would say that most women are fearful about what that mammogram is going to result in. And boy, if that finds some abnormality, even if it’s not cancer, it is a scary situation for most women. And it’s kind of out of the proportion for how clinically significant it is because there are plenty of other cancers like lung cancer, colorectal cancer that don’t inspire the same sort of fear in women yet are much more deadly. So I think I and others are hoping that by trying to identify different kinds of cancers and different kinds of precancerous, we can do a better job of being able to tell patients which ones are the ones that we really need to act on urgently and which ones are not an emergency and could probably be managed with a lot less invasive treatments that we’re currently offering.

Chris Riback: What is COMET? How is it designed? What do you hope to learn? Where are you in the study?

Dr. Shelley Hwang: COMET was born out of what we were talking about before. A patient of mine who very early in my career was diagnosed with DCIS, she came to see me. And even though she had a very small area that was involved, she decided to have a mastectomy. I was really just starting my practice and hadn’t thought too deeply about things during my training. DCIS was considered a cancer, and if you have a cancer, you cut it out. So that’s what we did. And the patient chose to have a mastectomy, and over the next 10 years that I continued to see her, I just saw that it affected her in a way that she never was able to regain her life. It interfered with the kinds of social interactions she had, the way that she viewed herself and her body. And it really got me thinking about whether I really needed to have done that mastectomy for her because it had clear long-term implications that affected this patient’s life in a very profound way.

Dr. Shelley Hwang: And so I think that started the quest of wanting to know whether DCIS really was a cancer and it should be treated as such, or whether there could be a different way of managing DCIS. And the one thing that became pretty obvious to me at the outset was that there are different kinds of DCIS, even though it’s all called the same diagnosis and the reaction by the surgeons is the same, but by understanding that there are different types with different likelihoods of actually becoming cancer in the future was really the genesis of the idea that there could be some women with very low risk DCIS who could be safely managed. For instance, if a woman, one of the 60,000 women that gets diagnosed every year goes to a surgeon’s office, now she’s only offered one option for management for DCIS, and that’s surgery. But what we are proposing is that if a woman has one of these low-risk DCIS conditions, and we can talk about that as well, but if a woman is identified to have a low risk DCIS, she has less than 1 percent per year likelihood of getting cancer.

Dr. Shelley Hwang: And so to take a hundred patients like that and operate on all of them, which is what we’re currently doing, is not a really effective way of taking care of these patients. And so we let biology dictate which patients should have the more aggressive treatment and which patients can be safely monitored. So the COMET trial was, I have to say, it met with a lot of criticism when we first proposed it. This was a prospective randomized trial, meaning women enter the study if they fulfill the eligibility criteria for low-risk DCIS, they can’t have invasive cancer. And they are randomized, meaning they’re selected to be in one group or the other randomly. And one group patients are monitored very closely. And in the other group, they undergo surgery right away just as we would do for anyone else who’s diagnosed with DCIS. And then we followed them over the course of the next five to 10 years, and we have successfully recruited almost a thousand women, so 997 women who were randomized as of January of 2023. So now we’re really excited to wait for the results of the study, which should be able to publish and report out in the next 12 months or so, and we’ll do an early look to see if it’s safe to keep patients on close surveillance rather than operating on them right away. And I think in the future as even better treatments evolve, those are the things that we want to offer to patients with low risk DCIS including things like DCIS vaccines, which would really reduce the need for these patients to get surgery.

Chris Riback: It is such a steep change that you are describing. Why do you think you faced the pushback that you faced and why is moving to something like active monitoring and such a, I don’t know if it’s an emotional challenge, an intellectual challenge. Why is it such a challenge?

Dr. Shelley Hwang: Yes, Chris, I think it involves all of those things. Breast cancer and the fear of breast cancer is so pervasive in our society that it is not only a medical issue, it is social, it is cultural, it is emotional. It affects women in so many different ways. And I’ve just been really fascinated by all the different components of that. I think anytime you propose something that’s really different from the status quo, people are going to be uncomfortable with it. And all I’m proposing is that there’s a question here that needs to be answered. I don’t know the answer to that question, which is why we need to do a clinical trial to find out. And the first thing we need to do is make sure that a monitoring approach like we use for early-stage prostate cancer, it’s very similar that we’ve got to show that it’s safe for women.

Dr. Shelley Hwang: And that’s what we’re trying to do with a COMET study. So hopefully we will be able to establish safety for once and for all because a prospective randomized trial is the gold standard of clinical trials. And once we establish that early safety, I think we’ll have a foundation where we can build other less invasive treatments for patients with DCIS there, I’ve seen thousands of patients with DCIS over my career, but it’s exciting to me to think that’s where we learn from the COMET study is something that will help all those women with DCIS out there that I’ll never get a chance to meet.

Chris Riback: Well, it’s certainly not lost on me. I’m sure not to anyone listening to you either that it is obvious and understandable why you would so greatly appreciate a patient’s desire and ability to ask y because it certainly sounds like that’s among the questions that you ask. We’ve been doing it this way for X number of years Y and that’s I guess just part of what you’re investigating. What’s next then in the study with 997 women? Is that, are you done in terms of women entering the study and now you’re just kind of, as you said a moment ago, anticipating the various results and standing by for that? What’s next in terms of the study itself?

Dr. Shelley Hwang: Yes, so there are a couple of things that are happening right now. One is that there is another international study that’s still accruing in Europe, and it’s based in the Netherlands, and it’s called the LORD Study. That study is continuing to enroll, but unfortunately, you have to be in Europe to be included in the study. The cool thing about that is that it’s not a randomized study, it’s a patient preference trial. Women who are entering the study get to decide whether they want to have surveillance or whether they want to have surgery. And in my last conversation with the primary investigator for that study, about 70 percent of patients who are entering the study are choosing to have active surveillance. So as always, when there’s a big change in how we’re thinking about some sort of medical issue, it’s really driven by the patients. This is what the patients are telling us that they would prefer.

Dr. Shelley Hwang: So we’re doing work together with the investigators for that trial, but I’m also looking to try to do something a little bit different because I think with technology now, you’re really not confined to having one patient, one physician in one geographic location. I think what we can do is have a virtual clinical trial where we could enroll patients from every country in the world, no matter where they find themselves dealing with a DCIS diagnosis. We can collect their images, we can collect their samples of tissue and blood, and we could inform women about what their individual risks for having cancer are. I had love to see that happen. We’re working to see how we could collaborate with people to bring something like that about. But thinking about an international reach to what we’re doing is super exciting. And I think the other technology and advancement is we’re working with some partners to see if we can identify a marker in the blood, which may be more accurate than anything else that we have right now that can help us to determine whether patients have an increased likelihood of DCIS becoming invasive cancer. So it’s an exciting space. There’s still a lot to do, and I think COMET’s just the first step in what I hope will be the right direction for patients.

Chris Riback: Well, I know that you’ve looked at work and done work international, including Africa, and I am aware of some of the work that you’ve done, including with Dr. Hope Rugo who was a previous guest on this podcast. So it makes sense that understanding just a little bit of your trajectory, what you’re describing makes total sense to close out just very quickly. There’s so many inputs into the work that you do. What role has BCRF played in your research?

Dr. Shelley Hwang: Oh my gosh. I’m so happy that you asked. The COMET trial was funded by a federal agency called PCORI, and they said, great idea. Set up the clinical trial and we’ll help support it for you. And we said, well, one of the things we really need to do is collect patient-reported outcomes. We need to collect tissue samples and blood samples and mammograms. And they said, good luck with that. That’s not something that we’re interested in funding. So we went to BCRF, we knocked on a lot of doors, and BCRF stepped up and they said, we understand how important it is to correlate clinical outcomes with biologic specimens because that’s the future. And without BCRF, we would not have had the extensive biobank of hundreds of samples of patients who participated in the study. And that’s the future of where this research is going. So incredibly, incredibly grateful to BCRF and a lot of friends who are there to help support this work and really be able to share with me the vision of where this research could go.

Chris Riback: Dr. Hwang, I was really looking forward to this conversation and I understand why. Thank you so much for your time and more importantly for the work that you have been doing and continue to do every day.

Dr. Shelley Hwang: Thank you. It was a pleasure.