Researchers at the Broad Institute and Dana-Farber Cancer Institute are using social media and patient advocacy groups to connect directly with metastatic breast cancer patients around the country and study what makes them genetically unique.
Within the Metastatic Breast Cancer Project, researchers are using Facebook, Twitter, and patients' own online networks to cast a wide net, enroll a diverse cohort, and investigate the genomic characteristics of "outliers" — those who have had extraordinary responses to cancer therapies and those who are traditionally underrepresented in research.
Although genomic advances have led to the discovery of new, molecularly defined treatment strategies in cancer and to the development of a number of precision drugs, the genetic markers of interest are often rare, showing up in as few as 1 percent of patients.
For example, Pfizer in 2011 received regulatory approval for Xalkori as a treatment for the 5 percent of non-small cell lung cancer patients who have ALK rearrangements. Four-and-a-half years later, Pfizer received approval for Xalkori in NSCLC patients with ROS1 rearrangements based on data from 50 people — an impressive number when one considers that the marker characterizes 1 percent of tumors.
Given the rarity of druggable markers in cancer, researchers are taking to social media to broaden their search. "It's really hard to find patients with any particular phenotype that you might be interested in if you're only looking at a single institution or city," Nikhil Wagle, assistant professor of medicine at Dana-Farber Cancer Institute, told GenomeWeb. Wagle and his colleagues wanted to figure out ways to identify patients with the genomic and phenotypic characteristics that could help them answer the research questions they were investigating, without having to wait for them to walk into their institutions.
An oft-cited statistic is that around 85 percent of cancer patients receive care at community hospitals, which places the research and investigational approaches at major cancer centers out of their reach. "So, the vast majority of adults with cancer have not had their tissue studied. The tissue in pathology departments is used for clinical purposes, but then they get stored," Wagle said. "No one has really ever asked those patients if they would be willing to have their tumor studied."
The historically low clinical trials participation rate — around 5 percent — among adult cancer patients in the US was another motivating factor for the project. "That's an incredibly low number, and even among those patients, not everyone on the trial gets their tissue biopsied for study," Wagle noted.
His team decided to test out whether by using social media they'd have more luck enrolling patients into the Metastatic Breast Cancer Project. There is no cure for metastatic breast cancer, but the patients are engaged and connected. Importantly, there is a strong network of advocates supporting patients.
Half a year before the project launched in October 2015, Wagle's team partnered with advocacy groups and patients with a strong presence on Twitter and Facebook, as well as individuals who write blogs, newsletters, and have extensive email lists. The project now has its own Twitter hastag (#mbcproject) and Facebook page. The study investigators, including Wagle, are active on social media to get the word out.
"Where we have seen the most traction is when other patients put something on their own Facebook pages and Twitter feeds," Wagle said. "This has started to spread even more organically as a patient-driven movement over the last several months."
Patients interested in joining the Metastatic Breast Cancer Project fill out an online form and provide information about their cancer. They also give consent allowing Broad and Dana-Farber researchers to contact healthcare providers to gain access to their medical records, including previous lab and genetic test results, and any stored tumor samples.
Participants also receive a spit kit in the mail so they can provide a saliva sample and researchers can compare their tumor genomics to their "normal" genomic data. Investigators at the Broad will perform deep exome sequencing and RNA sequencing on tumor samples, and standard exome sequencing on saliva samples.
Sending spit kits to study participants' homes is becoming a popular strategy in genomics research. 23andMe ispiloting such a service as an easy way help researchers incorporate genomic data in their investigations. One of the largest autism studies launched last week is similarly allowing participants to sign up online, and is mailing spit kits to their homes as a way to lessen the burden of participating in research.
In the first six months that the Metastatic Breast Cancer Project has been open, 1,800 men and women from all 50 US states, and even some from other countries, have signed up. More than 95 percent of patients have completed an online survey, answering questions about their metastatic cancer diagnosis, the treatments they received, how they did on treatment, and demographics.
More than 1,000 people have given researchers consent to collect their medical information and leftover tumor samples. More than 200 participants have mailed their saliva kits back to the project, and researchers are just starting to sequence patients' tumor tissue.
So, far Wagle's team has procured tissue and medical records for dozens of patients. He noted there have been a few cases where the tumor tissue was already used up, or the sample was more than a decade old and no longer stored at the institution.
Collecting information this way, Wagle and his colleagues want to explore the genomic characteristics of extraordinary responders. The National Cancer Institute is also studying these types of patients and defines extraordinary responders as patients who've had a complete or durable partial response to treatment in studies where less than 10 percent of participants responded.
Extraordinary responders have been a research interest at Dana-Farber for some time. Two years ago, a Dana-Farber-led team performed whole-exome sequencing on a bladder cancer patient's tumor DNA and pinpointed two concurrent mTOR mutations as likely responsible for the patient's 14-month complete response on the combination of Novartis' Afinitor (everolimus) and GlaxoSmithKline's Votrient (pazopanib). Four other bladder cancer patients in the same study had stable disease for four to five months. The two mutations identified in the extraordinary responder hadn't previously been reported in human cancer, the study authors said at the time.
Within the 1,800 patients who have signed up for the Metastatic Breast Cancer Project, Wagle's team has already identified a few patients who report impressive responses to the chemotherapy capecitabine. "We don’t have a biomarker for capecitabine, or [know the] reason why a small group of patients have extraordinary responses to that drug," he said.
Another group has shown extremely good outcomes on platinum chemotherapy. "We suspect based on other data that people who have DNA damage deficiency in their tumors might be particularly responsive to platinum chemotherapy," Wagle said. "But maybe there are other genes beyond BRCA1 and BRCA2 that might be mutated in the cancers and we should be able to discover those."
Wagle and his colleagues hope to focus on understudied metastatic breast cancer subgroups, such as women younger than 30 or 40 years old. It's not common for younger women to get metastatic breast cancer, but when they do, they tend to have a particularly aggressive form of the disease. Similarly, researchers hope to learn more about the 5 percent to 10 percent of patients who have metastatic or stage IV breast cancer from the outset.
"We're also particularly interested in using this approach to reach out to communities of patients who have been underrepresented in prior genomic studies, in particular minorities," Wagle said. "It's a real priority for us to be able to understand the underlying genomics of African-American and Latino women's metastatic breast cancer and really try to make the study representative of all the people who get [this disease]."
The Metastatic Breast Cancer Project is being internally funded at the moment, and investigators are still figuring out budgetary needs. There is no target enrollment goal, though Wagle hopes that several thousand patients will join in the first few years. In the coming months, Wagle's group will use social media to enroll patients into other projects focused on rare cancers, such as angiosarcoma, which affects the inner lining of blood vessels.
"Now this infrastructure and network we're building is about patients sharing their data and samples in order to help accelerate research," he said. "But once we build the infrastructure and once this process is in place, a great next step could be to help patients enroll in clinical trials or help identify the right therapies for them. That's certainly something we're thinking about."