Most people know that breast cancer is treatable and may be curable in many cases. But public images, of survivors who live and thrive after treatment can betray the unfortunate reality for a large cohort of patients, mainly women, who live with incurable, stage 4 disease. Until now, the National Cancer Institute (NCI) couldn’t say how many people are living with metastatic breast cancer.
A new report, led by Angela Mariotto, a statistician and investigator at NCI’s Surveillance Research Program, provides some clarifying facts. The work comes from five authors: two with the NCI SEER group, Ruth Etzioni, a biostatistician at the Fred Hutchinson Cancer Research Center in Seattle, and two with the Metastatic Breast Cancer Alliance (MBC Alliance).
The researchers estimate that this year, some 154,800 women are living with metastatic breast cancer (MBC) in the United States. Most metastatic cases are found as recurrences, typically some years after an early-stage breast cancer diagnosis. The community of U.S. women living with metastatic breast cancer is scattered across ethnic, geographic and age groups. And it is growing: The researchers estimate the number affected in 1990 was 105,354; in 2013, it was 138,622—reflecting a bump in the MBC population by approximately a third in just over 12 years.
Survival for people living with MBC remains in what can only be considered as unfortunately low range. Yet the report offers slightly good news: for women ages 15–49 found to have metastatic disease at initial diagnosis, median survival rose from 22.3 to 38.7 months, from 1992-1994 to 2005-2012. For women ages 50-64, the increase was less pronounced: median survival climbed from 19.1 to 29.7 months. For MBC patients in the younger group, five-year relative survival doubled in this time frame, from 18% to 36%. Among younger and middle-aged women with MBC, over 10% are living 10 years or longer after diagnosis.
Dr. Lynne Penberthy is a director of the NCI’s cancer surveillance program and an author on the new paper. She leads work to expand the kinds of data encompassed by SEER, so that epidemiologists and other researchers at the NCI can study trends, survival and recurrences in patients with specific cancer subtypes. We spoke by phone.
“At SEER, we’re getting better at tracking recurrences,” she said. “Our goal is to be able to monitor people from diagnosis to death, including each metastasis and recurrence, and not just for breast cancer. We want to do this for all cancer types.”
“Fortunately, people are living longer with metastatic cancer,” Penberthy said. “For breast cancer, there’s a large population to consider. This is the first time that we’ve been able to get some estimate. This is a population with significant medical and other needs.”
The researchers estimated that approximately three in four women with MBC have a personal history of early-stage breast cancer, meaning that most cases are recurrences. Only 26% of MBC patients had stage 4 breast cancer de novo, at first diagnosis. Yet most cases of breast cancer are found early, and the proportion of those with early-stage tumors who will develop recurrences remains unknown.
The total number of U.S. breast cancer survivors exceeds 3.5 million. Those living with stage 4 disease, now estimated at 155,000, account for only 1 in 22 or 23 survivors. That’s a small fraction, but because breast cancer is so common and often strikes women who are not yet old, MBC patients represent a significant group within the U.S. population who live with a chronic or terminal condition and stand to benefit from new treatments.
Understanding the factors that lead to breast cancer recurrence in some cases, and predicting which early-stage cancers are likely to cause metastases if additional (“adjuvant”) treatment is not given, is crucial. The number of invasive cases exceeds 250,000, and non-invasive (DCIS and LCIS) cases exceed 61,000, each year in the United States. So, hundreds of thousands of early-stage patients’ decisions, for more or less therapy, are at stake.
“It’s surprising that these numbers are not more readily available,” said Katherine O’Brien. At age 51, she lives in Chicago and blogs at I Hate Breast Cancer. She’s been living with metastatic breast cancer since 2009. “I’m on Xeloda now,” she told me in a phone interview. “This is my fifth line of treatment, and I’m doing all right with it.”
O’Brien advocates with the Metastatic Breast Cancer Network, a member organization of the MBC Alliance, and co-chairs the Alliance’s task force on metastatic breast cancer awareness. She has put forth a Change.org petition to count all people living with metastatic breast cancer.
“I appreciate the care SEER has taken to determine this fact,” O'Brien said, regarding the estimate of 155,000 people living with MBC. "Oftentimes you just see statistics in the introductions of papers, or in talks at conferences, and they’re just accepted, and not discussed or questioned.”
“We need this information because you can’t manage what you can’t measure,” O’Brien said. “When you don’t know the scope of the problem, how can you address it effectively? And if you don’t know the number, then it’s easy to minimize it.”
“Right now, we have pretty good information on how patients are treated initially," Penberthy said. "We are starting to capture more information on chemotherapy. Longitudinal data will inform prognosis at each decision point,” she said. “That’s our goal at the SEER program, to provide these data, so if patients get a recurrence, they'll have information to guide their decisions.”
“Now with electronic data and novel informatics, including natural language processing tools, we can capture more information and put the cases together,” she added. “For example, we get pathology reports now, so we can look at cancer subtypes.” That's crucial, because survival depends on subtype. “Whether you’ve got hormone receptor-positive or triple-negative disease, that speaks to what your prognosis will be. Patients need this information.”
“This is just the first step,” Penberthy said. “We’re doing everything we can think of to capture information on recurrences, but it takes time to do it carefully,” she added. “The SEER program has been around for a very long time. It’s very high-quality data. We’re part of the NCI. People trust SEER data, because we’re careful.”
“We know that patients and advocates want information on recurrences," Penberthy said. One way SEER is looking prospectively at breast cancer recurrences is through a collaboration with Genomic Health, the company that manufactures and provides OncotypeDx recurrence scores in early-stage invasive breast cancer and DCIS. “It’s going to be a while,” she said. “There’s not enough data yet on recurrences.”
Collecting detailed pathology data is “extremely challenging,” Penberthy emphasized. “For instance, OncotypeDx has been a reportable data point since 2010. But we found we were missing results for 43% of those tests. That’s almost half,” she said. “What was happening was that oncologists in the community would order the test, then the pathologist would send the results back to the oncologist, but the information never entered the hospital or other electronic medical chart.”
The new study provides no information regarding MBC subtypes, or for men with breast cancer. It finds that older women generally do less well. For all those over age 65, median survival remains around two years or less, and five-year survival below 24%. In general, patients appear to survive longer with known MBC when it’s found and treated as advanced disease at the time of first diagnosis, de novo, compared to MBC survival after a recurrence.
Marc Hurlbert is a study author who chairs the Metastatic Breast Cancer Alliance. That organization, led by advocates, receives support from approximately 30 breast cancer charities and 10 pharmaceutical and biotech companies, listed here. Hurlbert holds a Ph.D. in pharmacology. Since 2015, he’s been chief mission officer of the Breast Cancer Research Foundation (BCRF, an organization supported by my family, ES). A year after the Alliance’s October 2013 founding, it issued a landscape analysis identifying gaps in knowledge and research needs for people living with MBC.
“It’s exciting to see this information come to light,” Hurlbert said in a phone interview. “We’re headed in the right direction, but we still have a long way to go.”
“When the MBC Alliance reached out to the NCI SEER group, about the need for this data, they were incredibly receptive,” Hurlbert said. “They were already working on it, and our report put a fire under that work. Dr. Mariotto is so enthusiastic!” There’s more work forthcoming from the Alliance’s collaboration with SEER. “We will track breast cancer recurrences prospectively. We need more information on subtypes. And we need to look at quality of life.”
“This paper is the beginning, not the end, of better statistics,” Hurlbert said. “It looks specifically at women with breast cancer. What about men? There’s so much more to do.”
“We seem to be making progress,” O’Brien said. “But how can we know without survival data?” she said. “Knowing the recurrence rates and survival data for metastatic breast cancer is a big issue for patient advocacy groups.” We need a lot more information. “Oncologists may not think about it. They’re not epidemiologists,” she considered.
“Could anything be more controversial than the breast cancer recurrence rate?” O’Brien asked. “Everyone has their interest. The metastatic breast cancer patients won’t minimize it. People with early-stage disease might prefer more favorable statistics. Yet everybody wants to know.”
“We know breast cancer is not just one disease,” O’Brien said. “I’m cautious about the survival data. How do we know which patients those are, who are living longer?” Consider how much progress there’s been against Her2-positive breast cancer. “That’s been a wonderful success story. But for triple-negative disease, it’s not. While these numbers are encouraging, perhaps they don’t tell the whole story.”
“Keep in mind, this is real-world data,” Penberthy said. “Clinical trials include patients who tend to be younger, wealthy, and they tend to be white,” she said. “How do things go for the 96% of cancer patients who are not in clinical trials? What about older patients and people excluded from trials because they have cardiovascular disease? People need information on what happens in the real world, what happens to cancer patients who are just like them.”
“The challenge is, the farther out a patient gets, the longer they live, the harder it gets to capture information,” Penberthy said. Breast cancer recurrence can happen many years after an early diagnosis. In general, doctors are required to report patients’ initial cancer diagnoses, but they not obliged to report recurrences. Most of the NCI’s SEER registry data comes from hospitals. Oftentimes, reports of recurrence are received by doctors of cancer patients who are not in the hospital; they’re outpatients. “Finding their data is more difficult,” she said. “The metastatic diagnosis might come from a primary care physician, a radiologist or an oncologist.”
The SEER group is beginning to work with large pharmacies, she said. “Already we receive claims data from oncology practices and hospitals that bill for infusions of chemotherapy.” When someone has a history of cancer and starts receiving chemotherapy, that’s a clue for a possible recurrence, she explained. “But data on chemotherapy infusions doesn’t provide information on patients taking oral antineoplastic drugs.” Often, patients with recurrent and metastatic cancer take pills. “Data from pharmacies, for oral chemotherapy, will help us find recurrent cases.”
“I feel the sense of urgency,” Penberthy told me. “I believe that patients should be able to make informed decisions. I have a friend with a rare cancer, and unfortunately there were no data to inform his treatment choices." That speaks to why it’s important to have SEER funded, so that patients can have relevant and real-world information about their prognosis. “We’ll get there, it just takes a lot of work.”
