Genomics Project Heralds Democratization of Cancer Research

Lidia Schapira, MD


July 29, 2016

Editor's Note:Genomics studies have the potential to unlock new information about the molecular underpinnings of cancer. However, the challenge in studying tumors from patients with metastatic breast cancer has been that the vast majority of patients are treated in community settings where genomics studies are not conducted. To overcome this limitation, a team of Harvard researchers, led by Nikhil Wagle, MD, medical oncologist at Dana-Farber Cancer Institute, appealed directly to metastatic breast cancer patients, inviting them to donate saliva and tissue for the purpose of furthering clinical research. The early results of the Metastatic Breast Cancer Project were presented at the American Society of Clinical Oncology (ASCO) 2016 annual meeting.[1]

Dr Lidia Schapira, associate professor at Harvard Medical School, spoke recently with Dr Wagle about the astonishing response from patients, the current status of the project, and its implications for clinical research across several cancer types.

Researchers Ask Patients for Help

Dr Schapira: Tell us about what you do and what got you interested in starting this wonderful project.

Dr Wagle: I'm a medical oncologist at Dana-Farber Cancer Institute, and I run a research lab that focuses on breast cancer, both at Dana-Farber and at the Broad Institute of MIT and Harvard. The goal of our overall research efforts is to understand the genomic and molecular underpinnings of breast cancer and to figure out, if we can, the mechanisms of response and resistance to therapies, and identity new treatments or new treatment strategies for patients with advanced breast cancer.

We recognize that we can make huge advances in our understanding of metastatic breast cancer by studying tumor specimens from patients, especially when those specimens are linked to clinical information, response data, and other information that's contained within the medical record. But we also recognize that most tumor specimens, especially most clinically annotated tumor specimens, have not been available for these types of studies, because the vast majority of cancer patients are cared for in community settings where genomic research on tissue is not done. As we looked into it, we realized that most patients have never even been asked if they'd like to contribute their tissue samples and medical information for biomedical research.

Through social media and advocacy groups, the project empowers patients to accelerate research by sharing their tissue samples and clinical information.

The Metastatic Breast Cancer Project, which is a direct-to-patient nationwide study, was started to address this issue. Through social media and advocacy groups, the project empowers patients to accelerate research by sharing their tissue samples and clinical information.

Dr Schapira: This is an extraordinary idea for research in general. As I understand it, this kind of initiative can reduce the disparity that exists between patients who have access to high-tech testing and patients who perhaps have fewer opportunities to participate. Are women eager to participate?

Our hope is to democratize research, to allow any patient to say, 'Count me in,' and to share her medical information and samples, her opinions, and her voice.

Dr Wagle: Our hope is to democratize research, to allow any patient to say, "Count me in," and to share her medical information and samples, her opinions, and her voice.

We started about 9 months ago, and we've used primarily social media—Facebook and Twitter—and our partnerships with advocacy groups to get patients to sign up. Over 2400 people have signed up, and the numbers include people from all 50 states as well as other countries.

My sense is that the data are not yet representative. The patients who are joining are a little younger, probably because of the way we're engaging them. We don't yet have good evidence that we have enrolled sufficient numbers of patients from underserved communities or underrepresented minorities. A real focus of our project for the next year will be to understand how to be truly representative of patients with metastatic breast cancer.

Sharing Data and Opinions

Dr Schapira: What does participation involve? Do patients donate their tissue or saliva sample and then it's yours from then on? Or do they still feel they have some ownership in this project?

Dr Wagle: I think this is a really important point. They are donating to our project their tissue, their saliva samples, their medical information, and their opinions. They do this with the understanding that we are going to generate genomic information linked to clinical information, analyze the data, and make that database available to all other researchers.

There's definitely a sense that patients will always own their own data—that's an important point—and it is their right to share their data with the research community. If patients had the sense that we were going to collect this information and hoard it for our own research purposes, I don't think they would have participated. One of the reasons there has been enthusiasm around this project is that patients know that by joining, they're actually opening up their data to the world.

Dr Schapira: How many patients would you like to have, if you can dream big?

Dr Wagle: We would like to get many thousands of patients. We're on track to get several thousand in the first year alone, and we don't want to stop there.

The idea that patients across the country are participating in the research lends itself to doing all sorts of other projects.

The idea that patients across the country are participating in the research lends itself to doing all sorts of other projects. For example, you could imagine epidemiologic projects, you could imagine using the clinical information and the patient-reported information to learn very important things. You could imagine layering on a clinical trial infrastructure and helping patients with access to novel drugs. We want to keep this open and we want to recruit as many patients as possible to join this initiative. We want to continue to use it for different purposes.

Dr Schapira: How can primary care physicians or primary care clinicians help you? What part could they play in disseminating this message?

Dr Wagle: Patients trust their doctors; they'll often hear about something like this and ask their physicians if they've heard of it or what they think about it. So we want to create awareness of the project among physicians and in the medical community, both to help answer questions from patients and to talk to patients about the option to share their data—that doing so is low risk and that it can help advance treatments and treatment strategies for breast cancer.

Lessons Learned From Exceptional Responders

Dr Schapira: What treatments might emerge from this kind of research and analysis?

Dr Wagle: This type of approach can help us understand patterns from outlier patients or rare patients who exhibit a particular behavior that may not be typical among breast cancer patients but that may be very informative for all breast cancer patients. I'll give you an example. There is a small group of people who have truly exceptional responses to platinum chemotherapy. Their tumor may shrink altogether, may disappear, or they may be able to stay on the platinum chemotherapy for a very long time because it's working so well.

We don't have a full understanding of why a small subset of patients may respond so well to these drugs or other classes of drugs. By casting a wide net and enrolling thousands of patients across the country, there will be hundreds of patients among those thousands who tell us that they have an extraordinary response to a given drug. By studying their tumor samples and their saliva samples and understanding more about them, we might be able to identify the reason why this group of patients responds so well to this drug. We may be able to identify a predictive marker that helps us understand who should get platinum therapy earlier in their course of treatment.

Alternatively, we might be able to develop new drugs or new treatment strategies to make more patients respond in a way similar to the small group of patients who are naturally very sensitive. That's just one example of how studying the small number of outlier patients within a large cohort can help develop strategies that will apply to more patients.

Dr Schapira: That's fascinating. Have you thought of expanding this research to include patients who have diseases other than breast cancer?

This was intended as a proof-of-concept study that, if successful, could be replicated in other disease types.

Dr Wagle: Yes, we've thought about it a lot. My laboratory focuses on breast cancer and I'm a breast oncologist, and so it was a natural place to start. But this was intended as a proof-of-concept study that, if successful, could be replicated in other disease types.

We're encouraged enough by the results in the first 7 months that we started working on several additional cancer types. The next one that we will roll out will be in angiosarcoma, a rare sarcoma that would benefit from this aggregative approach to data. The cancer is so rare that no one center has studied enough patients to make any meaningful discoveries, but aggregating all patients with angiosarcoma around the country could be really powerful.

We're thinking about applying this approach to several other advanced cancers where we're badly in need of new therapies or new understanding of the biology. Ultimately, if this paradigm proves to be successful in multiple cancer types, you could imagine doing this not only for a subset of cancer but across all cancer. That would be the ultimate goal because you could democratize cancer research.

Can Moonshot Dollars Make Data Accessible and Intelligible?

Dr Schapira: As I listen to you, I'm thinking about Vice President Biden's Moonshot initiative to assign $1 billion to cancer research. In his remarks at ASCO,[2] he stressed the importance of global collaboration. What advice would you give Vice President Biden about how to spend this money?

Dr Wagle: That's something I've been thinking about a lot. I'm thrilled about the Moonshot effort, largely because I'm happy that this conversation about accelerating cancer research has entered the national consciousness. How can we work together? How can we break down silos? These are all things that we've been thinking about and talking about for some time.

We're also excited that a lot of the goals put forward by the Moonshot initiative are goals of the Metastatic Breast Cancer Project and future projects like it. So there's really a lot of alignment between what Vice President Biden said in his talk at ASCO and what we've been espousing as sort of core philosophies of our project. The Vice President announced at ASCO that the Genomic Data Commons from the National Cancer Institute (NCI), which will house genomic and clinical data, will be available for researchers to use. That's exactly the principle we're using for our data in the Metastatic Breast Cancer Project. Our plan all along has been to share our data with NCI's Genomic Data Commons, as well as with other shared databases.

Moonshot dollars will be allocated to serve seven different pillars to study cancer in many different ways. Thematically, the areas that could have the most impact and where the government could really play a big role are, as you suggested, data-sharing, by providing infrastructure that allows researchers as well as patients to be able to take their clinical information, their genomic information, and other information, information from experiments, and share it seamlessly across institutions. I think the data-sharing piece would be really, really powerful and something the government is uniquely positioned to do.

Another good use of this money would be in making sure that the information we're learning from genomic experiments and science gets into the hands of patients and clinicians so that they can use it for clinical decision-making. This complicated genomic information needs to become accessible so that everyone can take advantage of the advances in science.

Urgency Arising From a Patient Partnership

Dr Schapira: In your presentation at ASCO, I was very impressed by the fact that you were surrounded at your poster by advocates; clearly, they have incredible respect for the work you're doing. So my final question to you is on a personal level: What does this project mean to you and what have you learned?

Dr Wagle: This project is incredibly meaningful to me. I hoped that it would help us get answers in metastatic breast cancer more quickly. What I didn't anticipate was the tremendous outpouring of support from patients and advocates and how meaningful many of our participants find this project, and how eager they are to be part of it, to support it, and to go above and beyond our expectations to help make the project successful. Their support instills an even greater sense of urgency in our team to do something big and important with the data that they're sharing and to do it quickly. I feel it as a responsibility. Patients are going through all of this effort to share their information with us, and we have to be good stewards of that data and help others use it to make discoveries.

It's also a great reminder, even as a medical oncologist, to meet so many patients with metastatic breast cancer and hear from them and hear their stories. It's just such a powerful reminder of why we do this, why we care for patients, and why we do cancer research. In the research setting, we can sometimes lose sight of the people who are at the other end of what we're doing and really focus on a narrow problem. In this project there is a daily reminder of why we're doing this work.


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