Editor's note: This is the first of a two-part series on metastatic cancer. Part two focuses on the biology of metastasis — and what researchers don’t yet understand.
The women started comparing side effects as soon as the elevator doors closed behind them on the top floor of the Public Health Sciences building.
Beth Caldwell, currently taking an oral chemo drug, talked about her horrible fatigue, neuropathy and hand-foot syndrome.
“I have hillbilly feet,” the 39-year-old joked. “They always look dirty now. And every time I take a shower, chunks of skin come off. It’s super gross.”
Michelle Gherardi, a 48-year-old Seattle filmmaker who takes the same drug, Xeloda, gets severe body pain, enough that it’s sent her to the ER. Retired Bellevue fire captain Jeanette Woldseth was only able to take Xeloda for four days before she started having coronary artery spasms and had to stop.
The women, all metastatic breast cancer patients, came to Fred Hutchinson Cancer Research Center recently to meet with translational researcher Dr. Kevin Cheung and talk about the disease they’re all trying to eradicate.
Unable to find a sitter, Caldwell brought along her daughter, Maggie. After a brief lab tour, the 4-year-old perched on her mother’s lap in Cheung’s office, learning her ABCs on a video game while her mom and the three other women calmly discussed the disease that’s slowly killing them. This surreal mix of life, death and science is nothing new for the women — or for Cheung, a breast cancer oncologist. Since being diagnosed with MBC, the women’s lives have become a strange jumble of pain and patient advocacy, parenting and oncology appointments, social media and their own looming mortality.
But despite the fact that MBC kills 40,000 women (and men) every year, they’re not despondent. Rather, they’re encouraged by recent advances in immunotherapy and targeted treatments, and new initiatives calling for data sharing and a substantial increase in cancer research funding.
“I feel like this is the year,” Caldwell said. “I think the vice president is right. We are at this inflection point. There’s the cancer moonshot. And doctors are talking to each other across clinics now in a way they didn’t use to. And the 'metsters' are no longer being ignored. We’re forcing ourselves in. Before, we just laid down and died. Now, we’re lying down and having ‘die-ins.'”
A former civil rights lawyer and mother of two, Caldwell has worked hard to shine a light on metastatic breast cancer, i.e., cancer that spreads to other parts of the body and eventually causes death. Sadly, these deaths are often overlooked amid all the hot pink fundraising and survivor-focused hoopla.
Caldwell has co-founded the nonprofit activist group MetUp, lobbied for more research funding before Washington state legislators, met with Sen. Patty Murray’s staff in Washington, D.C. and organized three “die-ins” to raise MBC awareness. She’s also attended scientific conferences, helped to educate celebrity breast cancer patient Joan Lunden about the realities of metastatic disease and launched a petition to fold mets research into the official cancer moonshot goals.
And that’s just within the last year.
Caldwell and patients like her are part of a growing — and increasingly vocal — group of MBC advocates who are every bit as tenacious as the cancer that’s trying to kill them. Despite steady attrition (median survival is only two to three years following an MBC diagnosis), their collective voices have helped metastatic disease gain both awareness and crucial research funding.
Between 20 and 30 percent of women diagnosed with early stage breast cancers go on to develop mets. Maybe. No one really knows how many people have MBC (or the percentage of people who go on to develop mets) since the National Cancer Institute’s Surveillance, Epidemiology and End Results Program (known as the SEER Registry) doesn’t track recurrence or progression. It only counts you when you die of cancer — another sore point for metsters, who feel it’s an “unconscionable” oversight which, among other things, damages their ability to lobby for more research funding. No data, no dollars.
But that, too, is changing.
“SEER is working hard to test and develop methods which will help us capture this information, as we know it is very important,” a spokesperson for the Surveillance Research Program emailed in response to a question about revamping the Registry. “There are currently a number of ongoing pilot projects to look at possible approaches to capture recurrence, such as using claims and automating the review of electronic medical records.”
Over the last few years, nonprofits like MBC Alliance, Metastatic Breast Cancer Network and Metavivor.org have steadily brought attention to what some MBC advocates call “the elephant in the pink room” publishing reports, providing educational materials and resources, and distributing MBC-focused research funding (since 2009, Metavivor has handed out grants totaling nearly $2 million).
Now that work is beginning to pay off.
“I feel like there’s been a shift,” said Gherardi, who writes the blog, Dying to Know: A Metster’s Guide to Self-Advocacy Through Knowledge. “[But I’m still] taking meds from the 1970s and '90s.”
“It’s slow but it is starting to happen,” said Caldwell, who, along with MBC advocacy groups, credits #BCSM (breast cancer social media) and a raft of MBC bloggers like the late Lisa Bonchek Adams for bringing about the sea change. “Cancer organizations are being forced to listen in a way that nobody forced them to listen before. Half of Komen’s research funding now goes to mets. It’s still a tiny portion of their overall budget but at least it’s a start.”
Research that leads to less toxic treatment — and longer life — is what it’s all about for these women, not ribbons. As metsters put it on social media, #pinkisnotacure.
Cheung’s lab sits on the fifth floor of Fred Hutch’s Public Health Sciences building, one of three labs dedicated to metastatic breast cancer research. The physician-scientist was inspired to go into this research by his patients, particularly those who died.
They “whisper in his ear” and help put his research in perspective, he said.
Cheung and his team focus on tumor cell clusters, clumps of cancer cells that travel through the bloodstream in packs like “gangs of thugs” to set up residence in patients’ lungs, liver, bones or other organs. Cheung believes it’s these clusters — not single cancer cells that have escaped from the tumor — that are the drivers of breast cancer metastasis and perhaps even all metastasis. He hopes his discoveries regarding the clusters’ shared characteristics will lead to targeted therapies for patients like Caldwell, Gherardi and Woldseth, for whom there is still no cure.
“We want to get to some kind of therapy that will help people with metastasis,” he said. “Of all stages of cancer, of breast cancer, mets remains the key area we need to continue to develop.”
His latest paper, published in the Proceedings of the National Academy of Sciences in February, showed clusters are “led” by a highly expressed protein called keratin 14. He believes they’re “the bad guys” responsible for leading metastasis.
“It’s a team game the whole way through,” he said. “This gang of thugs breaks off at the primary site, gets into the bloodstream and then sets up shop in distant organs.”
Cheung’s research has also shown tumor cell clusters express genes that can enable certain properties. He hopes to one day develop therapies that will target the specific proteins that produce these properties.
“Every bad guy has a weakness,” he told the group earlier as they huddled around the time-lapse and stereo microscopes he and his team use to see the clusters in mouse-modeled metastases. “If we knew their secret weakness, we could figure out ways to defeat them.”
By delaying metastasis and its symptoms — organ failure, pain and complications — Cheung hopes to allow “MBC patients [to] live longer and also live a better quality of life.”
“All of us are happy to give tissue samples,” Caldwell said upon hearing his battle plan.
“Should we tell our oncologists that we want a piece of our tumors sent over here?” Woldseth asked.
“There’s a lot we can learn from studying metastatic cancer cells from patients,” Cheung said. “So, yes, certainly, when the time is right. I’m a big believer in community. Let’s all work together to fight metastasis.”
“You’ve got our back so we have yours, for sure,” Caldwell told him, the others nodding in agreement.
Grassroots partnerships like these, between terminal patients and the researchers trying to save them, are driving other initiatives like the Metastatic Breast Cancer Project, led by the Broad Institute of MIT and Harvard and Dana-Farber Cancer Institute.
Co-designed by MBC patients and launched in November 2015, the project has already enrolled over 1,700 women from across the U.S. and Canada largely through social media, including Caldwell, Woldseth and Gherardi.
So far, participants have signed consent forms and agreed to share medical records, treatment history, tumor tissue and more. Investigators are still in the process of collecting and analyzing the patients’ saliva, tumor samples and genomic data, but they have announced a few preliminary findings from patient-reported data. About 100 patients, for instance, have reported an “extraordinary response” to Xeloda, the MBC oral chemo drug that inspired such a wildly different side effects — and efficacy — in the women who visited with Cheung.
Also of note is the survival data.
While a group of 764 participants had survived an average of almost three years following a metastatic diagnosis, 50 participants had been living with MBC for more than 10 years.
“As a patient and as a scientist, I can think of no better or faster approach to accelerating our understanding of cancer,” said Corrie Painter, project director, who will discuss the MBC Project at Fred Hutch on Monday, May 23.
Much of the excitement in cancer research today has to do with this ability to glean potentially life-saving data from patients. As Vice President Joe Biden put it during his cancer moonshot visit to Fred Hutch in March, “we have to allow the data to actually yield the answers.”
And that is happening.
“We’re getting more and more data about the trajectory of a tumor over time,” said Fred Hutch researcher Dr. Peggy Porter, pointing to new technologies — and a new philosophy — that encourages oncologists to do genetic sequencing of not just the primary tumor but recurrent tumors and metastatic sites since the biology — and thus the treatment — at each stage may differ.
“It’s a real change in the paradigm to evaluate the biology of mets sites and treat specifically for that biology,” she said. “We don’t routinely test metastasis but we’re getting to that point where patients are going to be willing to have the additional biopsies and physicians are going to view this as standard of care. Researchers and clinicians can actually see a way forward.”
The science, Porter said, is finally starting to catch up with patients’ calls for help.
“Our ability to do something is now matching the advocacy,” she said. “Women will be saying ‘If you can get that much information out my met and will know how to treat me, I definitely want you to do that.’”
Head of the Breast Cancer Research Program, Porter is currently working with others to create a Metastatic Breast Cancer Initiative involving multiple Fred Hutch investigators and other Fred Hutch/UW Cancer Consortium partners, each of whom is attacking MBC from a different angle.
Cheung’s work in tumor cell clusters will be part of it, along with Dr. Cyrus Ghajar’s research on metastatic microenvironments and dormant tumor cells (read more about Ghajar’s Laboratory for the Study of Metastatic Microenvironments in Fred Hutch News Service's “The science of cancer spread” story tomorrow). Also represented will be Dr. V.K. Gadi, a breast cancer oncologist and clinical researcher who does translational research in early stage disease (including triple negative breast cancer) and is currently poised to launch an innovative Phase 1 immunotherapy trial involving microchimerism for patients with MBC.
The proposed initiative will also include large population studies. One will look at patient tumor profiles to help predict who is and isn’t at high risk for MBC; another will determine how lifestyle and behavior influence the development of MBC and a third will examine the benefits — and response — of bisphosphonates, drugs originally developed for osteoporosis.
“We hope to attack this not just with one person’s lab but by bringing together the considerable expertise in the Consortium,” said Porter.
Collaborations that fast-track research are crucial for patients with MBC, who have limited treatment options — and limited time.
“Drugs only work for so long,” said Caldwell. “That’s the thing with metastatic disease. You always need new drugs because they’re going to stop working and you’re going to have to try something else. And eventually you run out of drugs and you die.”
Until then, Caldwell, Gherardi and Woldseth will continue to rely on treatments developed decades ago, joking about their fatigue, pain, sloughing skin and other not-so-funny side effects. They’ll continue to lose friends and fellow advocates and navigate the strange jumble of their lives: testifying before lawmakers in Olympia one day, curled into a ball of pain at the ER the next.
Most of all, they’ll continue to reach out to researchers to forge partnerships, share data and push for a cure.
“I am feeling more hopeful that more time and money is being spent on metastatic breast cancer,” said Woldseth. “But there is still no cure.”
What there is, though, is collaboration and determination. And hope.
And as Cheung put it, “hope is good.”
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Diane Mapes is a senior editor and writer at Fred Hutch Cancer Center, who's written for NBC News, TODAY, CNN, MSN, Seattle Magazine and other publications. A breast cancer survivor and patient advocate, you can reach her at dmapes@fredhutch.org or doublewhammied.com / @double_whammied / @doublewhammied.bsky.social. Just diagnosed and need information and resources? Visit our Patient Care page.
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