Pictured above: Irene Ghobrial, MD; Sapna Syngal, MD, MPH; and Elizabeth O'Donnell, MD
Transforming Cancer Prevention
August 15, 2024
By Robert Levy
For more than 100 years, health advocates have spread the message that, with cancer, patience is not a virtue.
As early as the 1920s, the American Society for the Control of Cancer, the predecessor of the American Cancer Society, was distributing posters that asserted "Cancer is a curable disease if discovered early and treated at once." That note of urgency is embedded in what most people know about cancer: Early detection and early treatment offer the best hope of surviving the disease.
Today, as research has advanced, there have never been as many ways or reasons to deal with cancer promptly. Whereas cancer was once diagnosed primarily after symptoms appeared, it can increasingly be detected at its very onset — sometimes even before it becomes cancer. Research has also led to the discovery of an array of conditions that often produce no symptoms of their own but sharply increase an individual's risk of developing cancer.
At the same time, there are more steps that patients at risk for cancer can take to stave off the disease. In the not-too-distant past, learning that one had an inherited predisposition to certain forms of cancer was more likely to spur anxiety than a practical plan of action: in many cases, doctors had little to offer in the way of preventive strategies. Today, a variety of new surgical techniques and drug agents are being studied to help patients avoid cancers that once seemed almost inevitable. Watchful waiting — the practice of closely monitoring at-risk individuals until cancer actually develops, and then beginning treatment — is giving way to watchful action.
Dana-Farber has always been the place to go to have your cancer treated. As we move forward, it will also be the place to go to protect yourself from cancer.
Dana-Farber is seizing on these advances with the creation of its Centers for Early Detection and Interception. Launched late last year, the Centers bring together the Institute's existing programs in finding and treating early-stage cancers, and coordinates and expands them. They give people at high risk of developing cancer a "home base" at the Institute to learn about their risk, receive counseling on their options, be referred for treatment if necessary, and come for follow-up exams. And, because they're at Dana-Farber, the Centers serve as a hub for research – with investigators seeking to better understand cancer risk and how it can be reduced.
"Dana-Farber has always been the place to go to have your cancer treated. As we move forward, it will also be the place to go to protect yourself from cancer," says Sapna Syngal, MD, MPH, co-director of the Centers for Early Detection and Interception and director of research in Dana-Farber's Center for Cancer Genetics and Prevention.
Building on Dana-Farber's Legacy
The Centers for Early Detection and Interception are not so much a departure from Dana-Farber's traditional areas of emphasis as the embodiment of one of its longest-standing priorities. It's not an exaggeration to say that the field of inherited cancer risk has its very roots at Dana-Farber. It was at the Institute, in the 1970s, '80s, and '90s, that Fred Li, MD, helped demonstrate that people can inherit a genetic predisposition to develop certain malignancies. Li-Fraumeni syndrome, one of the first hereditary disorders found to predispose individuals to cancer, was named for him and his research partner Joseph Fraumeni.
Li and Fraumeni's work began with a conundrum: Why did some families develop cancer at unusually high rates? The scientific orthodoxy of the time said it was the result of bad luck, or perhaps viral infections or environmental exposures. Only after decades of detective work and collaborations with researchers in the emerging field of molecular biology did they trace the trail of familial cancers to inherited mutations in the gene TP53, a tumor-suppressor gene later dubbed the "guardian of the genome."
Today, people may be identified as having an elevated risk for cancer for a variety of reasons: they've inherited a gene linked to cancer or have already had the disease; they've been exposed to known carcinogens at home or on the job; they have a precursor condition — an abnormality that is often a forerunner of cancer; or they've had a positive result on a test that looks for cancer DNA in the blood.
Dana-Farber has seen each of these as an opportunity for disease prevention. The Institute was the first to conceive a program for early detection and interception of blood cancers and in 2018 established the Center for the Prevention of Progression, led by Irene Ghobrial, MD, Benjamin Ebert, MD, PhD, and Robert Soiffer, MD.
Leaders envision the Centers for Early Detection and Interception as a new "front door" to the Institute for such individuals. "We have a single phone number [617-762-2344] for people to call if they want to be evaluated — and a clear pathway through the Institute for their follow-up care," Syngal remarks.
The Centers for Early Detection and Interception offer specialized programs targeting different cancer types:
- The Center for Early Detection and Interception of Blood Cancers concentrates on people diagnosed with precursor conditions for hematological cancers, such as leukemia, lymphoma, and multiple myeloma.
- The Multi-Cancer Early Detection (MCED) Clinic works with people who have tested positive on a "liquid biopsy," a blood test that can detect DNA from more than 50 types of cancer.
- The Center for Early Detection and Interception of Solid Tumors helps people at higher risk for developing solid tumor cancers, including gastrointestinal, gynecologic, and head and neck cancers.
These centers represent the first phase of the program. They may ultimately be joined by similar clinics for every Dana-Farber disease center.
Giving Patients a Clear Path
Syngal describes what prospective patients can expect when they contact the Centers for Early Detection and Interception. "The call will be answered by a new patient coordinator, who works closely with an oncology nurse navigator to help the caller determine which of the early detection centers is best suited for their care," she relates. "The navigator becomes their guide to the Institute, letting them know what to expect when they arrive and accompanying them to their first appointment.
"After the individual has been evaluated at one of the centers, the navigator will help arrange follow-up care — scheduling appointments for monitoring, assisting with insurance authorizations, and being a point of contact. If the initial evaluation indicates the person has or might have cancer, or if they develop cancer later on, the navigator will help them transition to the appropriate Dana-Farber clinic for treatment."
Part of the Centers' mandate is to reach out to underserved populations, leaders say. A range of efforts — from hiring oncology nurse navigators experienced in working with historically marginalized communities to launching public education programs with churches and neighborhood organizations — are underway to ensure accessibility.
Tests like Galleri are screening tests, not diagnostic tests. A positive result indicates that further evaluation is needed.
Blending Research and Care
Here is a closer look at the primary Centers for Early Detection and Interception, the patients they serve, and some of the research projects they've undertaken.
Multi-Cancer Early Detection Clinic
Currently, recommended screening tests exist for only four types of cancer: breast, colorectal, cervical, and lung (only for tobacco smokers). Screening for prostate cancer is based on certain risk factors. Newly developed liquid biopsies, however, can detect DNA from dozens of types of cancer in a single sample of blood. The vast majority of those cancer types are not picked up by standard screening procedures. When this type of test — the Galleri® test is the most widely used — returns a positive result, it doesn't necessarily mean the person has cancer. But it does require follow-up.
"Tests like Galleri are screening tests, not diagnostic tests," says Elizabeth O'Donnell, MD, director of the MCED Clinic. "A positive result indicates that further evaluation is needed."
The MCED Clinic provides that evaluation. Open to people who test positive on Galleri or have questions about the potential benefit of MCED testing due to an inherited cancer risk, a personal history of cancer, or a strong family history of the disease, the clinic guides individuals through the next steps of diagnosis and treatment.
On the research side, investigators are rigorously evaluating the Galleri test itself. In one study, they're using it to screen 1,000 people with an elevated risk of cancer, either because they've inherited a cancer-related gene mutation or have a strong family history of cancer. The goal is to see if the test has additional value in higher-risk populations. Another study, funded by the U.S. Department of Defense, is evaluating the Galleri test in 1,500 veterans.
"Because these technologies are so new, there's a great deal to be learned about which populations can benefit the most from them, how often people should be tested, and what type of follow-up is best," O'Donnell observes. "It's exciting that this technology is arriving, but like anything new, it needs to be rigorously evaluated and implemented."
Researchers have also launched a partnership with Google to explore whether artificial intelligence can help identify people at risk for thoracic cancers based on the terms they use in internet searches.
Center for Early Detection and Interception of Blood Cancers
Research over the past few decades has shown that most hematologic cancers are preceded by precursor conditions – abnormalities in the blood that may develop into cancers. They include Clonal Hematopoiesis of Indeterminate Potential (CHIP), a precursor of leukemia and cardiovascular disease; monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma, precursors of multiple myeloma; smoldering Waldenström's macroglobulinemia (SWM); and monoclonal B-cell lymphocytosis (MBL), a precursor of chronic lymphocytic leukemia (CLL). Newly diagnosed, slow-advancing lymphomas such as follicular lymphoma and marginal zone lymphoma are also being evaluated in the center. Because these conditions usually don't produce symptoms, they're often found by chance — through a routine blood test, for example.
"Precursor conditions are more common than people may think," says Irene Ghobrial, co-director of the Centers for Early Detection and Interception, senior vice president of Experimental Therapeutics, and the Lavine Family chair for Preventive Therapies. "It's estimated that as many 5 to 10% of people over age 50 have such conditions, especially for blood-related cancers. Our center has three goals. First, improved screening, so precursor conditions aren't found incidentally. Second is risk stratification, to be able to determine which patients are most likely to develop cancer. Third, for those at greatest risk for cancer, we want to find treatments that intercept the disease process before cancer occurs."
The CHIP clinic sees patients with clonal hematopoiesis, a precursor of blood cancers like myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Directed by Lachelle Weeks, MD, PhD, patients evaluated in the clinic receive testing for acquired genetic mutations associated with MDS and AML. Weeks and Virginia Volpe, MD, counsel patients on the likelihood that cells with these mutations may one day progress to cancer. Each patient receives personalized management plans geared to their specific risk.
In 2023, Weeks and Ebert developed the clonal hematopoiesis risk score (CHRS), a tool that estimates a patient's risk of progression. Now used in hematology clinics worldwide, CHRS allows clinicians to determine if patients with CHIP have a high, intermediate, or low risk for progressing to MDS or AML. Weeks and Max Stahl, MD, are leading one of the first clinical trials to test the feasibility and safety of therapies to prevent leukemia in patients with high-risk CHIP.
The CHIP clinic also includes Dana-Farber's first community oncology nurse navigator, a role developed with the Institute's nurse leadership and Cancer Care Equity Program. The new position connects patients with unexplained and persistent blood count abnormalities, who have been seen at community hospitals, to care at Dana-Farber.
Aswin Sekar, MD, PhD, is spearheading the expansion of the center to include MBL, early-stage CLL, as well as newly diagnosed, slow-advancing lymphomas. He recently developed a method of identifying individuals with MBL based on genetic abnormalities in their blood. His colleague Inhye Ahn, MD, is leading a clinical trial for patients with early-stage CLL, and Reid Merryman, MD, is leading an early intervention trial for patients with follicular lymphoma or marginal zone lymphoma.
The center is leading other clinical trials of agents with promise for arresting the advance toward cancer. "We're increasingly able to intervene with treatments, especially immunotherapy, bispecific antibodies, CAR T-cell therapies, vaccines, and others," says Omar Nadeem, MD, the center's medical director.
One study is examining whether the diabetes drug metformin can prevent or delay the development of myeloma in people with high-risk MGUS or lower-risk SMM. Another trial, dubbed the PROFAST study, asks whether extended nightly fasting by people who are overweight and have MGUS, SMM, or SWM can prevent them from developing cancer. Several trials are looking at the effectiveness of certain drug combinations in keeping cancer at bay. For patients with high-risk SMM, these include the ImmunoPRISM trial of the drugs lenalidomide, dexamethasone, and teclistamab, and a phase II trial of daratumumab, bortezomib, lenalidomide, and dexamethasone.
Center for Early Detection and Interception of Solid Tumors
The gastrointestinal tumor center serves people with potentially precancerous abnormalities in the esophagus, stomach, pancreas, or colon. Such conditions include Barrett's esophagus (a change in the cellular lining of the esophagus), gastric intestinal metaplasia (cellular changes in the stomach lining), gastric neuroendocrine tumors, pancreatic neuroendocrine tumors, intraductal papillary mucinous neoplasms, and colon polyps.
Along with its fellow centers, the Center for Early Detection and Interception of Gastrointestinal Tumors participates in the InAdvance study, which collects information and tissue samples from people at increased risk for cancer. The specimens will be analyzed for clues to which individuals are most likely to develop cancer, and when, explains center director Nicolette Rodriguez, MD, MPH.
The Center for Early Detection and Interception of Gynecologic Tumors, launched in early 2024, sees people at increased risk for gynecologic cancers, including cancers of the ovaries, uterus, cervix, and fallopian tubes. That risk may be due to an inherited mutation in one of the BRCA genes, or to Lynch syndrome, a hereditary condition predisposing people to cancers of the female reproductive tract and other organs.
The center's researchers are evaluating a promising new screening test for ovarian cancer. It looks for specific microRNAs — small strands of RNA that help control protein production in cells — in a sample of blood. Participants in the study, who all have an increased risk of breast cancer, agree to have blood samples drawn twice a year for up to five years. Researchers will analyze the samples to determine if changes in the types and amounts of microRNAs indicate a propensity to develop ovarian cancer.
A second study, dubbed TUBA-WISP2, also involves people at increased risk for ovarian cancer. One traditional option for reducing that risk has been to have one's ovaries removed — between age 35 and 40 for people with BRCA1 gene mutations, and between 40 and 45 for those with BRCA2 mutations — a procedure that results in early menopause. Based on research at Brigham and Women's Hospital and other institutions, it's now clear that most ovarian cancers begin not in the ovaries but in the fallopian tubes.
"The TUBA study challenges the need to remove ovaries at the traditional ages and may allow individuals to keep their ovaries longer if the fallopian tubes are removed earlier," says Colleen Feltmate, MD, director of Minimally Invasive Surgery in Gynecologic Oncology.
"Dana-Farber is disrupting the traditional way of thinking of cancer," Ghobrial remarks. "We will not wait for cancer to happen and then we treat it, we are going to be proactive by early detection and early interception to prevent cancer before it starts."
