Dr. Lisa Carey on Breast Cancer Research & Care at UNC

Falk: So there are receptors in addition to estrogen receptors that have helped in that thinking. If I were listening and I wanted to understand these different receptors, all that have funny names that distinguish one kind of breast cancer from the other. Let’s walk through those different word choices and what they really mean to a patient who’s listening to their physician tell them their cancer is “estrogen-receptor positive,” or other receptor positive. Help me with all of that.

Carey: So when we categorize breast cancers, we do it on the basis of the clinical extent of the cancer, which is an old-fashioned way – Stages One, Two, Three and Four.

Falk: What does that mean?

Carey: That means, how big is the cancer, and where has it spread to? Stage One, for example, are very small tumors that haven’t left the breast. They’re really encased within the breast tissue itself. They’re not in local lymph nodes, they aren’t in any other organs. Stages Two and Three are a little bit bigger or they have started to spread locally, and Stage Four is cancer that has spread into distant organs. We think of Stages One, Two, and Three as being curable, Stage Four as being controllable but not curable. That nomenclature and the old, sort of way of looking at cancer, including breast cancer, as an anatomic disease still exists and is still important.

To this anatomic categorization scheme, now we have factors that represent the biology of the breast cancer, and there are old-fashioned ones-the estrogen receptor and the progesterone receptor, which give us a sense of the hormonal sensitivity of the cancer—those have been tested for years and years, although the testing techniques have gotten better recently compared to what they did in the olden days.

There’s another test that we use right now, and that’s for a protein called HER2. HER2 is a gene that creates a more aggressive kind of breast cancer when it’s turned on. In about twenty percent of breast cancers it’s turned on and it’s not regulated the way normal genes are managed. Actually the cancer cell no longer can regulate its own growth. In those breast cancers, the cancer tends to be much faster growing and we can test for it. It’s also important because we have drugs against it. So, just as we have anti-estrogens, now we have anti-HER2 drugs. Those are the three factors that we test for now, in part because they give us a hint about biology and also because we have drugs against these particular factors.

Falk: Estrogen, progesterone, and HER2.

Carey: Correct.

Falk: If you have any of those receptor markers, it helps you identify a prognosis and it also helps you identify treatment options.

Carey: Absolutely. We treat them differently.

Falk: The word choice “triple negative,” that implies all three of those receptors are not expressed or available in the tumor. Is that right?

Carey: That’s right. It means they are negative for all three which means we have chemotherapy to offer, but we don’t have any of the targeted therapies at this time, although this is an area of very active research. Now it is important to note—and this is something that I think sometimes gets missed, because the Internet is full of stories about triple negative and how it’s aggressive and has fewer treatment options—the truth is, that many triple negatives, if not most, are actually still curable, we just don’t have targeted therapies.

Falk: When you use the word “curable,” what does that mean? Cure for the rest of the person’s life? They don’t have to need screening, or follow-up? What’s the breast cancer definition of “cure”?

Carey: The breast cancer definition of cure is that you live a long and healthy life and you die of something else, with no evidence of your cancer coming back once you finish the initial round of treatments.

Falk: That’s just a remarkable statement to be able to make.

Carey: Well, years ago—my grandmother died of breast cancer in the 1960’s. And into the early ‘70’s, more than half of women who were diagnosed with breast cancer died of it. That number’s now twenty percent or a little less.

Falk: And it’s against this progress then that you can overlay the genetic studies that people like Chuck Perou have been doing, and hopefully that’s going to lead to further refinements in our thinking about these diseases.

Carey: You know, it already has. Among the things that have come out within the last ten years are really applying these genetic tests to existing cancers and trying to get additional information beyond ER, PR, and HER2. For example, the molecular subtypes of breast cancer that Chuck first discovered—those particular subtypes have been now turned into a genetic test that you can use to help gauge, within hormone receptor positive breast cancer, whether a cancer’s more or less likely to do well with just anti-estrogen therapy—and there’s actually several commercial tests that do exactly that. They help us decide who needs chemo, and who can get just an anti-estrogen pill for five or ten years, and not have to have additional therapy. That kind of application of these genetic tests is where we want the whole field to go.

Falk: You just spoke at a summit in June called the Cancer Moonshot Regional Summit. What’s the moonshot?

Carey: Well, the moonshot is Vice President Biden’s initiative. Essentially what he wants to do is accelerate the rate of cancer research—basically double it by the infusion of a directed amount of money going explicitly to cancer research. He is particularly focused on the cancer centers to leverage this kind of additional funding particularly well, and he’s challenging people. He’s challenging people in our community to accelerate what we think we can do by two-fold. The cancer moonshot visit that we had was something that they did nationwide, and stakeholders from the various cancer centers, particularly comprehensive cancer centers, kind of all came together in your respective place and we all put on Internet connections with Vice President Biden and people who were having their meeting in DC. We were all sort of linked together electronically. He gave a lovely talk about what he wanted to accomplish and then we were expected to have a conversation locally about what we thought we could do and the way in which we thought we could bring into our communities better cancer research to help improve patients’ lives. I had the pleasure of talking about what I thought UNC particularly would be valuable in doing in that regard.

Falk: You use the term “comprehensive cancer center.” What constitutes a comprehensive cancer center and what makes it different than an oncologist in practice someplace else?

Carey: Well, the National Cancer Institute designates cancer centers. To be a cancer center, in general that means you do not just do patient care, you also do research that is directed towards moving into the clinic. Comprehensive cancer centers—and there’s now forty-seven of them around the country—now you’re narrowing down to a subset of typically academic medical schools and the affiliated cancer centers that do particularly well what’s considered to be clinical care, clinical research, basic research, and the interface between them—what we call “bench to bedside” kind of research. The comprehensive cancer centers are those that have met the criteria, which is reevaluated every five years. By investing money in them, they can deliver on improving patients’ lives with cancer.

Falk: Why, as a patient, would you want to get care at a comprehensive cancer center, rather than someplace else?

Carey: There’s a very strict set of criteria that says this is a place that knows how to take care of patients, knows how to be at the cutting edge of research, and knows how to bring that research to the clinic as fast as possible. If I was a patient, I would want to be seen at a comprehensive cancer center because that would be my best chance of being in the forefront of new advances in therapy.

Falk: The comprehensive cancer centers in the state of North Carolina include UNC, Duke…

Carey: And Wake Forest. There are three of them.

Falk: Out of forty-seven that’s remarkably good.

Carey: Yes, our state has done well.

Falk: You also very much participate in the Alliance for Clinical Trials in Oncology for breast cancer. There’s a committee you have a very important role in. Can you tell us about what you’re doing for this Alliance for Clinical Trials?

Carey: Yes, the National Cancer Institute also invests in what are called national cooperative groups. These are essentially big structures to do clinical research broadly across the nation. There are four of them in adult oncology. The Alliance is one of them. Within the Alliance there are hundreds of participating institutions, some are academic medical centers, some are private practices that just want the opportunity to participate in practice-changing research, so this is not the kind of research that’s done—so at UNC we do a lot of research that are pilots, where we’re testing new things and seeing what looks like it’s going to be beneficial for patients. Once you’ve gone through that process and you think something looks really promising, it goes into the national level. These are essentially the kind of trials that change what I do tomorrow when I go to clinic. I have the pleasure of being one of the co-chairs of the Breast Committee for the Alliance, which means that we help decide what are going to be the next trials, where are our gaps? What do we want to encourage, what do we want to invest in? And then, when the trials are done, we help design them and deliver them. I lead it with a colleague who is a specialist in what we call Health Services Research, she’s a particular expert in how is cancer research disseminated, and where are the gaps in how patients are actually treated in real life? She is, in a sense, my book-end. The two of us have become the two new co-chairs, as of May.

Falk: Congratulations.

Carey: Thank you. I do think it’s a terrific opportunity and we’re going to do our best to take great advantage of it. I’ll give an example, the kind of thing we do, because I led one of the recent Alliance studies where we were asking a question about the best way to treat HER2 positive breast cancer. We did a trial where we were testing either taking two drugs against HER2, or one drug, in addition to the standard chemotherapy. When we designed it, we designed it so that all the patients in the study—there were 400 of them—would also have biopsies for research. We did deep genetic evaluations, and interestingly, we found that while the drugs were sort of important in whether the cancer responded or not, actually there were a whole bunch of factors that were specific to the tumor or to what we call the micro-environment—the area around the cancer, the immune cells, and things like that, that are actually even more important.

That gives us a road map for asking smarter questions, not just questions about drugs, but actually designing trials and trying to be much more rational. If we’re going to give more therapy to someone, we’d better make sure that they need it. And if someone doesn’t need that much therapy, for example if we can omit chemotherapy, then we should learn how to do that. So that’s the kind of thing that I’d like for us to continue to do.

Falk: There are lots of clinical trials at UNC, lots of clinical trials at Lineberger. Why would a patient want to participate in a clinical trial? What is in it for them?

Carey: Well, there are a couple of big reasons that patients should participate in clinical trials. The first is, it may give them access to something that they would not have access to otherwise. Our hot new drugs are tested in clinical trials first, and until they’re approved, you have to be on a clinical trial in order to receive them. I think an even more practical reason for many patients—I mentioned the marked improvement in breast cancer outcome. Over the years by participating in trials, we’ve gotten smarter and smarter. Trials are usually our best idea for what we think is going to improve our standard of care. So by being in the trial, you can be part of that.

Moreover, all of the patients that I treat now, most of their therapy is guided by the trials that went before. So there’s an altruistic element– by participating in a trial, you’re helping a person who is going to be sitting in your seat next year or the year after, five years down the road—that’s a very real benefit for us as a community. We really depend on our patients to be our partners in this. Trials are a very good way to do that.

Falk: If you could wave a magic wand and change what we’re doing now in breast cancer therapy, wave your magic wand over the next twelve months and tell us where you think things may go, and wave that same wand where you hope things are in five years or so.

Carey: I have to say that one of the things we’ve been very invested in is studies that build on each other, through the Carolina Breast Cancer Study, which is a long-standing study at Lineberger Comprehensive Cancer Center and the School of Public Health, and that study has helped us understand the differences between older women and younger women in terms of prognosis from breast cancer, differences between black women and white women. We are just now starting to understand some of the differences amongst these groups in how the cancer behaves, and understanding there’s a biologic part of it, which we may be able to improve on by understanding the biology better.

There’s also clearly -and in spite of it being 2016—there’s still an access to care problem, and it’s playing out in our patients particularly with what we consider to have the good breast cancers. I would say in the next twelve months, we are in the analysis phase of the third Carolina Breast Cancer Study. What’s already coming out is a lot of information about what are the root causes of the differences in survival from breast cancer. I would say in the next twelve months we’ll have a much better feel for that and will have instituted studies to circumvent and intervene on the problems that keep people from getting effective care.

I would also say in the next twelve months, through my Alliance hat, I anticipate us to have developed some more trials like the one I mentioned, where we embed our scientific pursuits and our clinical ones together, so we’re asking treatment questions and also “why” simultaneously.

Five years from now—five may be fast, but in the very beginning we talked about how if you acknowledge that breast cancer is a family of diseases and we can’t say “what causes breast cancer?”, we have to say “what causes the different kinds?”. My own hope, and what we haven’t talked about, is prevention, because we haven’t been very effective in that. I’m not talking about early detection but actual prevention where somebody actually doesn’t get breast cancer, and we haven’t budged the number of people getting breast cancer at all. We may have improved survival but the same 200,000 women a year are getting it as were getting it ten, twenty years ago. My hope is that we will have a much better understanding of who gets which kind of breast cancer, because we already are learning that the risk factors for the different kinds may themselves be different, which gives us an opportunity again to go back and say we can do a better job of prevention than in those early studies that were done a long time ago before we had this more sophisticated understanding.

Falk: It sounds like, from what you have been describing, is there really is hope for patients with breast cancer, and there’s a reason for those folks standing out with their pink signs raising money and awareness for breast cancer. It’s a consequence of experts like you who have helped move this field forward.

Falk: When we think about breast cancer care at UNC, it’s more than one individual, it’s more than Lisa Carey who’s the name and the face associated with this disease to a certain extent. There are lots of members of this breast cancer treatment community at UNC. Can you spend a few moments describing who they are and what they do?

Carey: Absolutely. Breast cancer patients do better when they are treated in a multidisciplinary sense. When we say multidisciplinary, that means that the medical oncologists—people like me, and my colleagues, who are quite remarkable, and I’ll mention a couple of them in a second. But the surgeons, the surgical oncologists, the radiation oncologists who specialize in breast cancer, are all actually talking together and communicating and working together on a unified treatment plan. We also have involvement from our radiologists and pathologists and geneticists. When we talk about multidisciplinary care, when we go to clinic on Wednesdays, we all come together and we spend an hour and a half going through complicated cases and deciding what we think is the best thing to do for them. Many of the patients come, and if they’re seen on that day, and they stay in the room and we come to them. They don’t come from one doctor, and then a few days later, another doctor. We actually get an integrated, unified decision-making from all of us having had communications and having reviewed everything together before hand. That’s one piece of it, and it’s what I think is a really important piece of it.

Falk: It’s certainly easier for the patient.

Carey: Yes, it’s one day they’re there, and they stay in the room, and we come in and out. It’s “one stop shopping.” It’s also important to note that I may be the person who’s been here the longest in medical oncology, but Hy Muss is probably one of the most famous people in the nation in geriatric oncology, a very key element of this. My colleague Carey Anders has developed a brain metastasis clinic with neurosurgeons and radiation oncologists which I think may be a unique clinic. Claire Dees runs early drug trials. Katie Reeder-Hayes is an expert in how do patients actually get treated in the community, and she is oftentimes a reality check for all of the things we think we’ve advanced for new drugs—if they’re not getting to the patients, she’s the one who points that out in places where we need to do better. My surgical colleagues are remarkable and there’s great advances being done both in surgical oncology management as well as plastic surgery. Same for the radiation oncologists. To that we add the scientists. Several of us actually routinely spend a couple of hours a week with the scientists in Lineberger who are doing the evaluations and advances on the scientific bases, and we interact with them very frequently, so I would consider a multidisciplinary team to include them. We help them understand what the clinical challenges are, so that they’re doing research that’s focused in the clinic, but they help us too.

Falk: A really good reason for a patient to want to have that comprehensive, multidisciplinary and translational science care here at UNC. Thank you, Lisa, so much for spending time with us today in our Chair’s Corner.