Clear Search

Unraveling the Mysteries of DCIS with Dr. Shelley Hwang

By BCRF | May 20, 2024

Dr. Hwang discusses why we need to better understand the biology of stage 0 breast cancer

Researchers are urgently working to advance our understanding of ductal carcinoma in situ (DCIS) to prevent overtreatment. DCIS is the earliest, non-invasive form of breast cancer, which why it’s sometimes called stage 0 breast cancer. Right now, DCIS typically treated like invasive, early-stage breast cancer, because there isn’t a way to predict which cases of DCIS will progress to full-blown invasive breast cancer. The ambiguity can be particularly challenging for patients who are unsure of what the best course of action is.

But new discoveries are helping change assumptions and evolve decisions about how DCIS is treated. Researchers like Dr. Shelley Hwang are hoping to identify less invasive, more customized approaches to care for this condition.

Dr. Hwang is the director of the Breast Cancer Disease Group at Duke Cancer Institute, vice chair of research in the department of surgery, the Mary and Deryl Hart Distinguished Professor of Surgery, and a professor in the department of radiology. A BCRF investigator since 2016 and recipient of the Tanger Factory Outlets Award, Dr. Hwang is a nationally recognized figure in pre-invasive disease and DCIS, and she leads or participates in several collaborative efforts on this topic, including the Cancer Research UK “Precision” study and Ithe randomized trial of DCIS active surveillance known as COMET. Dr. Hwang was named one of TIME’s 100 Most Influential People in 2016 with BCRF investigator Dr. Laura Esserman.

Below is an edited transcript of their conversation. Find the full conversation here.

Chris Riback: Talk to me about ductal carcinoma in situ (DCIS). What is it?

Shelley Hwang: So 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.

CR: Why is this controversial?

SH: Back in the day, we always used to think that DCIS would turn into cancer. 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.

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. I and others are hoping that by trying to identify different kinds of cancers and different kinds of pre-cancers, 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.

CR: What is the COMET study?

SH: I wanted to know whether DCIS really was a cancer and if it should be treated as such, or whether there could be a different way of managing DCIS. For instance, if a woman, one of the 60,000 women that gets diagnosed [with DCIS] every year who 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, she has less than 1 percent per-year likelihood of getting cancer.

The COMET trial is a prospective randomized trial, and one group of 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 follow them over the course of the next five to 10 years, and we have successfully recruited almost a thousand women, so 997 women who 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.

CR: It is such a steep change that you are describing. Why is it such a challenge?

SH: 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.

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.

CR: What’s next for the study?

SH: So there is another international study in Europe called the LORD Study that is continuing to enroll, and we’re doing work together with the investigators for that trial. 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’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.

CR: What role has BCRF played in your research?

SH: I’m so happy that you asked. We needed funding for the COMET trial, and 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.