Investigating Breast Cancer: Dr. Nikhil Wagle
By BCRF | October 4, 2017
By BCRF | October 4, 2017
We begin today with a statistic that is immediately concerning and curious: mortality from breast cancer is higher in black women than in white women. Among the challenges in studying this problem is a lack of data. That's because only a small fraction of the cancer genome atlas, that's the catalog of genetic mutations responsible for cancer, is comprised of African American patients. That's just one of the many obstacles in investing breast cancer that Dr. Nikhil Wagle is trying to solve.
Dr. Wagle is assistant professor of medicine at Harvard Medical School and medical oncologist at the Dana-Farber Cancer Institute, where he also is deputy director of the Center for Cancer Precision Medicine. Another hat that Dr. Wagle wears is leading the Metastatic Breast Cancer Project, a wide ranging effort to gather more breast cancer data, particularly from under-represented populations. I think you'll really enjoy this conversation. Dr. Wagle connects the personal with the science.
As you'll hear, one of his key lessons from years of research, the importance of bringing on patients as partners. You'll also hear something that I found more surprising. In an age of seemingly infinite scientific innovation, one of Dr. Wagle's key tools to building the data base? Social media. You can follow him on Twitter, @NikhilWagle.
Dr. Wagle, thanks for joining me. I really appreciate your time.
Dr. Nikhil Wagle: Thanks for having me.
Chris Riback: We are going to go deep into your science and your research, both of which are phenomenal. You are saving and will directly save lives. I just want to start with a point of curiosity and what may be your second biggest impact, which is Twitter. 4200 followers, 6400 tweets, 29,000 likes. One doesn't often see someone who sits at the intersection of extraordinary science and extraordinary use of social media; but there you are.
Dr. Nikhil Wagle: That's funny that you say that. I don't think I intended Twitter and social media to become a major part of my research. I would say it has become that. I think largely because it's a way for us as scientists to really directly connect with patients. Social media, there are a lot of bad things about social media, but there are a lot of great things about social media. One of them is to be able to communicate with people in ways that you wouldn't be able to if you had to rely on them coming to your institution.
Chris Riback: It's fascinating. Given what you do and we'll talk about that now, and obviously the very human aspect of what you do ... I would assume that having a way to connect in that way is through social media, in a more human ... whereas so many of us have this image that, 'Well, to be able to connect with our doctor or with a researcher, we need to make an appointment,' and it's three months out if you're lucky and six months out. You can't ever connect. I would think that to have kind of a quasi-regular means of interaction and where you're distributing ideas and connecting via social media. That's an interesting new way to think about, and maybe connects with a very human aspect of medicine that you practice. Is that right?
Dr. Nikhil Wagle: Yeah, I think that's right. I don't practice medicine over Twitter. I think understanding how we can use social media is important. It's exactly what you said. It's the ability to use the internet, social media and otherwise, to connect with people who you otherwise wouldn't able to connect with, I have found is really important for our research and in general, to build this community of physicians, and researchers, and patients who are working together. It's also been incredibly useful for me to just learn, to learn from patients, to learn what's important to them, to learn about them, to learn about what's going on in their lives. It has been tremendously valuable both in conducting research and also designing research.
Chris Riback: A real listening feedback loop.
Dr. Nikhil Wagle: Right.
Chris Riback: That's terrific. I'm sure it does give you insights that you might not have otherwise gotten. Let's go from those insights to some of the other statistics, the serious statistics and the science statistics, which is where your research starts, is how I understand it. Obviously, if I get this wrong, you will very freely and graciously, of course, just correct me.
To begin, the serious statistics. Mortality from breast cancer is higher in African American women than in Caucasian women, or maybe than in non-African American women. You can actually maybe even just help me to make sure that we've got the statistics straight, and that I'm characterizing it correctly. Describe, if you would for me please, the situation and the numbers.
Dr. Nikhil Wagle: Sure, it's true that black women get breast cancer at earlier ages. They tend to get more advanced stages of the disease, and they tend to die more frequently from breast cancer. There are a number of disparities that some of which can be explained by health disparities, and others of which may be differences in biology. There's been a lot of work looking into that. One of the things we're really interested in is to understand the differences in tumor biology and try to see if we can try and address some of those disparities.
Chris Riback: Talk to me about that research and maybe what your hypothesis is. You obviously, like so many people in your situation, do a number of different things. If I understand correctly, this part of your research is part of the Metastatic Breast Cancer Project. We'll talk separately about your lab and the work that you're doing there. On this project, describe looking at the tumor biology. What is the scientific process, and what's your hypothesis? Because looking at that component of a difference, a race-based difference, it's very interesting to a lay person like me, to be looking at the tumor biology aspect of it and the scientific aspect of it. I'm sure many others are looking at the social aspects and so many other inputs that could go into anything.
Dr. Nikhil Wagle: Right.
Chris Riback: Talk to me please about your scientific process and your hypothesis.
Dr. Nikhil Wagle: Sure. Well, one of the major things that we look at in my lab is the underlying genomic and molecular architecture of breast tumors. The reason we do that is we try and see if we can identify the reasons that breast cancer grows, why it might metastasize, why it might respond to certain therapies and become resistant to other therapies; and really why it might form in the first place.
There have been, over the years, a number of very large studies looking at breast cancer, the largest being the Cancer Genome Atlas Study, which is funded by the U.S. Government. The problem with many of the existing studies in breast cancer and otherwise is that the patients that were represented in those studies, and the tumor samples that were collected and analyzed in those studies, are not great representations of all of the different people who are affected by breast cancer. The vast majority of patients who were enrolled and participate in the Cancer Genome Atlas Study were white. Although we have a pretty good sense of the underlying genomic architecture for primary breast cancer from that study, it is not a representative sample. We don't yet really know if that information that we learned there can be applied, for example, to black women who get breast cancer.
One of our questions is if we were to conduct a landscape of breast cancer, and in particular of metastatic breast cancer to look at the genomic and molecular architecture in patients with different racial and ancestral backgrounds, are we going to see differences? That question's still a pretty open question.
The Metastatic Breast Cancer Project is a project that we started a couple of years ago where we can partner directly with patients using social media, Twitter, Facebook, the internet, advocacy groups and other patients who go out and help us enroll other people that they know with metastatic breast cancer and really form this network of patients who are willing to contribute their information or their samples, or their medical records to this research study. By doing so, it allows us to create, to cast a much wider net than we would be able to if we were just relying on studying patients who are cared for at our institution in Boston. This really provides the opportunity to now ask those questions of questions about different groups of patients who get breast cancer.
One of the studies that we're doing in the Metastatic Breast Cancer Project is to focus in on African American women and African American men who get breast cancer, to really try and understand the underlying genomic and molecular architecture of their disease.
Chris Riback: You are literally, you and others, are literally trying to bring together a community that has been under represented in these studies historically, and trying to bring them together and say will you join us? Will you open up? Will you us see your and analyze everything from your medical records to, I would assume, tissue samples, or maybe more. It's asking a lot. It's a lot under normal circumstances. It feels almost like you're having to go outside of traditional scientific research lab means. We already talked about it. You're using social media as one of your channels to build that network. How's that going? Am I characterizing it correctly? How challenging is it? How's it going for you so far?
Dr. Nikhil Wagle: Yeah. I think you have characterized it correctly. The idea is that ... the vast majority of cancer patients are cared for in community settings where they receive their cancer care but they aren't necessarily going to big academic medical centers that conduct the kinds of research that I was just talking about. The vast majority of cancer patients have not contributed their information or their tissue samples for research, but largely because no one's really ever asked them. The hypothesis behind the project was that if we reach out and ask patients to partner with us and ask them if they would be willing to share this information, that they would. So far, in the first couple of years of running the Metastatic Breast Cancer Project, I think that hypothesis is proving to be true.
We launched the Metastatic Breast Cancer Project in October of 2015. In the two years, almost two years since we launched, nearly 4,000 women and men with metastatic breast cancer from all 50 states have signed up.
They've told us who they are and where they live, and answered a number of questions about themselves and about their cancer. Many of those patients, over 2,000 of those patients, have gone the next step and given us permission to collect their medical records and their tumor tissue, and their salvia samples, and perform sequencing studies on those samples, and create this public sharable database that we're going to let all researchers use to be able to start to understand the connections between their clinical data and their molecular and genomic data.
Chris Riback: That's a really important point. One of the outputs, maybe it's the output, ... again, you correct me please if I've gotten it wrong. One of the key outputs of the work that you're doing is this searchable database. This will be data information that other researchers who may be looking at various aspects while you're looking at the tumor biology. People may be looking at other aspects of what's going on they will have access to [the database]. You're building the population, I guess the 'and' that might not have been big enough historically, and making that sharable. Is that right?
Dr. Nikhil Wagle: That's right. Our view is that patients are willing to share this information and share their own medical information, and their samples with us. When we collect and generate that data, it's only fair for us to share it with the world. This is the ultimate, as you said, the ultimate output of this project is this very rich database that has genomic information, medical record information, and importantly, patient reported information that anyone can look at. It's de-identified, so it's not like you can look up an individual, but you can look up characteristics. You can look up the details of the tumor type, or the drugs that someone got, and the mutations in the tumor, and start to look at patterns.
We're going to do our first data release this fall, around our two year anniversary of the first tumors that we sequenced, connected to all of the clinical data from the medical record as well as the patient survey data will be released. We'll do updates to that database every six months thereafter.
Chris Riback: That's excellent. I assume that your lab is equally taking advantage of the data and starting to do your own types of studies in your own discipline against it. If that is what you're doing, I assume that it is, how far along are you on that? Do you have any hypotheses around that, around the research aspect or the science aspect maybe, of your accessing the data.
Dr. Nikhil Wagle: Yes. That's a great question. We certainly plan to do that. I will say that it was important for us to get the data out into the public domain first. Historically, typically what people do is, and understandably, they will collect data. They will analyze it. They will make a discovery. They will write a paper. Then, if the data is shared, it will be in the context of that paper and subsequently, the data will be shared. We wanted to make sure that sharing the data was the first thing we did. That data will be shared now so that everyone can start looking at it. Then, we're going to start digging in to questions that are of interest to us and to my laboratory.
There are many questions that we're interested in. Our lab, in particular, studies response and resistance to therapies in breast cancer. Some of the questions that we're interested in looking at the Metastatic Breast Cancer Project data for are studying patients who may have had unexpected extraordinary responses to certain things. In this data set, there are patients who got a particular therapy and unexpectedly either had dramatic shrinkage of their tumor, or were on a particular drug for a very long time, longer than expected. We want to study those tumor samples and see if we can figure out ways or reasons that an individual's tumor may have responded so well to a particular drug.
Because we have the numbers, because we're collecting so many patients, we can actually start to look for patterns amongst similar responses. If a dozen or a hundred patients all had a really dramatic response to a particular drug, and there's some commonality amongst those hundred patients, then maybe we can identify a marker that we can go forward and look for in other patients to say, to see who should get that drug in the future.
That's one example of a study we're interested. There are a number of others I'm happy to tell you about. We definitely have questions that we want to ask, but we know that there are many other questions out there that others want to ask, too, so we can all do that together.
Chris Riback: Because these data represent perhaps a previously under-represented portion of the population, is one hope ... and maybe it's not. Maybe this is just ... this doesn't pertain or it wouldn't follow accurately. But is one hope that maybe by getting, again, a previously under-represented data set and types of patients, that maybe one will discover things that weren't discovered previously, that you might hitting into a portion of the population that may be able to provide biological or scientific insights that simply because they didn't have data or sufficient data on them before. One wasn't able to notice important outcomes.
Dr. Nikhil Wagle: Yes. Yeah, I think that's a good way to put it. I want to emphasize that it's a work in progress.
Chris Riback: Yeah.
Dr. Nikhil Wagle: This data release that's coming out this fall is just the first sliver of data from what we hope to be a very large and very representative group. Now, we haven't solved the issue of diversity and making sure this data set is representative. We have a lot of work to do, and we're working with patients and advocates to try and make sure that diverse communities are participating in this project. We certainly hope to have this represent lots of different people who get breast cancer. That's something we're working on.
To your question, the data that we're going to put out there now and that hopefully we're going to put out there in even large volume in the future, is different from existing data in a number of different ways. One of them is hopefully that it represents different groups of people that may not have been well represented in previous studies. That may include differences in race, and ethnicity, and ancestry; a inclusion of rarer groups of patients who get breast cancer. For example, men with breast cancer will be represented here. Patients with rare sub-types of breast cancer, for example, like lobular breast cancer or inflammatory breast cancer.
In one way it's different is the representation of different groups of people, or different types of sub-types of cancer. The other couple of ways that it's really different, I think at least three additional ways. One is that this database represents all patients ... or all of the patients in this study are patients who developed metastatic breast cancer. Breast cancer that spread beyond the breast that we currently don't have a cure for. The big studies to date have represented primary breast tumors from patients who may or may not have ultimately gone on to get metastatic breast cancer; but the vast majority of the patients in this study did not go on to get metastatic breast cancer. That's one difference.
A second difference is that we have connected the genetic information, the genomic information here with detailed clinical data and patient reported data. That is something that's been sorely lacking in the field to date. We've had clinical studies that look at medical information or patient reported information. We've had genomic studies that look at the details of the genes that are altered. Rarely have any databases connected these two pieces of information. I think that's going to be the key to really trying to look for patterns in responses to therapies or prognosis, or sites of metastases, things like that.
I would say the third thing that's different about this study is that when possible, we are collecting serial samples. Not just the original tumor, but a metastatic tumor, if we were able to get a portion of the metastatic tumor, or self read DNA. Looking at blood samples, looking at self-read DNA from later in the disease course to be able to really try to track the evolution of the cancer, and look at resistance. Those studies are starting to emerge from multiple places now. That's a third way that this is different.
Chris Riback: Well, connecting all of that, you don't have a researcher or scientist to see just a really full picture. It's sounding like a much fuller picture than you would normally get. That's a data coming together at once. Let me let you give just a quick commercial, I guess if you will. How should somebody, if somebody does want to join this community, or get involved, or see if their information would be useful to you or to the study overall? How should they reach out?
Dr. Nikhil Wagle: Yeah, that's great. Patients who have metastatic breast cancer, anyone with metastatic breast cancer can participate. They do that by going to our website, which is www.MBCProject.org. We also have a Facebook page and a Twitter account, as you said. I would say that just kind of learning about the study and if someone's interested, even just telling us about themselves.
Just saying "I'm here, this is my name, and I have metastatic breast cancer." Even that is helpful. Then patients can decide how much more they want to participate, whether they want to answer questions about themselves, or consent to sharing their saliva and their tumor tissue, and their medical records. All of those are additional steps that one can take. I would say anyone who's interested can come to our website and read about the project, then even just do the simple step of identifying themselves.
Chris Riback: Yeah, that's terrific. I would say as well, I watched ... There's a blog and I watched one of the videos. It really does give a very comfortable sense. You had some of the patients on there as well. They talked just very, very, very humanly about, and comfortably about not only some of the current challenges and the historic challenges of getting involved, but also the why they have, and some of the benefits, and how that can be a way to really help others. Yeah, very, very powerful, powerful stuff.
Tell me as well, just to start to wrap up. Tell me about you. How did you get into this? I mean going back, where did you grow up? For you, was it always science? Was it always research? Did you ever think perhaps you'd be a fiction novelist instead? Then, once you got into this road, how did you end up on this specific path?
Dr. Nikhil Wagle: Yeah. Well, I grew up in New Jersey. I think I went through the usual run of different things I wanted to be when I grew up, certainly; but science was always a really big interest of mine, from a very young age. As I got later in school, biology became a huge interest of mine. Both my parents are physicians. My dad's a psychiatrist, my mom's an internist. Medicine was something I was also exposed to from a very young age. The idea of taking care of patients and helping people are sick was something that was always very appealing to me.
The idea of becoming a physician scientist ... came naturally, I'd say, when I was in college, and then ultimately medical school. Oncology really ... it spoke to me for multiple reasons, both the human aspect of people with cancer. It's a really terrifying disease that in many cases, we didn't have great treatments for, and in many cases, weren't able to cure. Also, the scientific aspect of it, which was the fundamental biology associated with cancer and all of these things that we needed to understand and the ways that treatments were developed was really appealing to the scientist in me. It was a pretty natural fit.
Chris Riback: As you've really been at the forefront in this battle to cure breast cancer, and as you've really combined .. you really are or do sound like you're at that intersection of the humanities and the science, and the human component, and the medical scientific component. Is there some aspect of it that you wish people heard better or understood better? The multi-pronged approach to really trying to find a cure for breast cancer. Is there something that folks, that you've heard or that a kind of insight that you've gained that you wish folks understood better?
Dr. Nikhil Wagle: Yeah. I think this has been an incredible learning process for me. I've gained a lot of insights about how to improve research and how to accelerate research. Two things stand out. The first is, as you said, this multi-pronged approach that interdisciplinary nature of science and this type of research is hugely beneficial. We have a tendency, myself included, to go to our silos and work on the thing that we know about, or we're good at. It's really hard to work in these interdisciplinary teams, and combine expertise from really different areas. When it works and when it's possible, I think it's incredibly powerful.
The second insight and the main thing I would like everyone to know is how important it is and how valuable it is to have patients as partners in cancer research, and probably research in general, I would say. That we started the project with this notion that we want to partner with patients that only they have the information about themselves, and so they can contribute to research in a unique way and help accelerate the process. That's true. It's even so much more than that, that by bringing on patients as partners, by helping ... by having them think through the design of the study, the questions we ask, the things that are interesting, the things that are important, the sense of urgency, the human elements, as you say.
All of that has contributed so much I think to this project. I can just see how is really important to other projects, to other research. I think patients should know that, that how important their views are to research. Researchers should know how important it is to truly partner with patients, regardless of what kind of work they're doing. I think as we move towards that, I think it's going to really enhance and accelerate the type of work we do.
Chris Riback: That's wonderful. That's excellent. Yes, that is. That's really important for all sides to keep in mind. Dr. Wagle, thank you so much for your time. Your humanness really comes through. It's really evident in how you talk about your work and what motivates you. Thank you for your time very much, and thank you for the work you're doing.
Dr. Nikhil Wagle: Thanks for having me, and thanks for talking about it.
Chris Riback: That was my conversation with Dr. Nikhil Wagle. See what I mean about his humanity? I loved his insight about bringing on patients as partners. Remember, if you want to follow him on Twitter, it's @NikhilWagle. My thanks to Dr. Wagle for joining, and you for listening. To learn more about breast cancer research or to subscribe to our podcast, go to BCRFCure.org/podcasts.
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