by Steph Guerra
figures by Rebecca Clements

It has been one year since President Obama announced the Cancer Moonshot Initiative. Since then, the Moonshot has convened a Blue Ribbon panel to brainstorm ten recommendations to be completed over the course of the next five years. In this series of articles, I will explain the science behind some of these proposals with an aim to evaluate their utility and feasibility. This first article focuses on a new buzzword in the cancer community, and a major focus of the Moonshot, Precision Prevention.

A lesser-known sibling of Precision Medicine, Precision Prevention applies a similar strategy to preventing the disease, namely that preventing cancer is not a one-size-fits-all feat but rather, a process that should be custom-tailored to the individual patient. Though this precision has most often been applied to treating cancer patients, there is increasing interest in applying these same principles to prevent cancer from ever forming. Precision prevention imagines a world where you and your doctor can devise an action plan that utilizes your own biological, epidemiological, behavioral, and socioeconomic characteristics to stop cancer before it starts.

Stopping cancer before it starts

A 2016 study from Harvard estimates that over half of cancer deaths can be prevented by lifestyle changes such as smoking cessation, alcohol moderation, healthy weight maintenance, and physical activity. This conclusion came as a startling (albeit hopeful) discovery to the cancer research community at large. Encouraging and implementing low-cost lifestyle changes may be the key to drastically lowering the rate of cancer deaths worldwide.

Figure 1: Healthy lifestyle could prevent half of all cancer deaths in the United States according to a 2016 study that examined data from two large ongoing health survey studies. Researchers divided the cohort of 100,000 patients into two groups classified as high-risk and low-risk. Members of the low-risk group maintained a health lifestyle, which included not smoking, alcohol moderation, regularly exercising, and a BMI between 18.5 and 27.5. Researchers found a lower incidence of cancer and lower number of cancer deaths in the low-risk group and extrapolated their findings to the general population. This type of study is called a prospective cohort study. There are approximately 600,000 cancer deaths in the United States each year so each person in the figure represents 10,000 deaths.

Cancer researchers have worked hard to design new treatment regimens for this deadly set of diseases, but despite decades of research, cancer death rates remain high and cancer rates are increasing globally. Treatments are indeed getting better, but they are by no means a guarantee of survival. The only way to guarantee cancer survival is to prioritize not getting cancer in the first place.

It seems like a silly thing to say. Of course we should try our best to not get cancer. But on a national level, the United States does not prioritize cancer prevention research. Out of the National Cancer Institute’s $5 billion dollar proposed 2017 budget, only 4% is directed toward research on cancer prevention and control. Meanwhile, 28% is directed toward researching effective treatments with an additional 49% directed toward understanding the causes and mechanisms of the disease. But thanks to the dedication of an entire Cancer Moonshot recommendation, cancer prevention is finally taking some of the spotlight.

How do we prevent cancer?

Traditional cancer prevention mechanisms focus on primary prevention, or choices and changes that can be made to prevent cancer from starting in the first place. Figure 2 showcases some of the more common interventions that combat key cancer risk factors. Some interventions are personal lifestyle choices including maintaining a healthy weight and choosing not to smoke. Others involve institutional regulations. For example, some cancers such as mesothelioma are caused almost exclusively by exposure to environmental hazards such as asbestos. To prevent these types of cancers, key interventions include restrictions on the usage of carcinogenic agents via guidelines recently implemented by the Lautenberg Chemical Safety Act in 2016. And still other interventions include public health measures such as vaccination programs and occupational health protocols.

Figure 2: Seven environmental risk factors for cancer are represented in chart with their associated intervention strategies. Some cancers, such as those caused by viral pathogens can be prevented by vaccine implementation. In fact, vaccination programs currently exist to prevent infection with the four pathogens that account for more than 90 percent of pathogen-associated cases of cancer including HPV [Data: National Cancer Institute].
Early detection is another key tenet of cancer prevention because research has shown that early detection leads to a drastic increase in survival rates. Screening tests are especially useful for cancers that develop from detectable precancerous lesions. For example, colon cancer is often preceded by the growth of polyps in the colon and rectum. These abnormal growths can be easily detected by regular colonoscopies, and if intercepted at this early time point, actions such as surgery can be taken to prevent cancer from developing and spreading across the body.

Screening to intercept cancer before it starts has many benefits, but too much screening in the population can also result in adverse events such as false-positive tests that cause both emotional and financial burdens. A crucial issue within cancer prevention is to determine how to implement screening measures to detect the highest number of cancers with the least amount of consequences. Adding precision medicine strategies to these decisions promises to change the course of cancer prevention.

Putting the Precision in Prevention

The Precision Prevention working group from the Cancer Moonshot initiative recommended a combination of screening implementation research, big data mining, scientific discovery, and public education to make prevention work efficiently at the population-level. Going beyond the traditional prevention measures requires accurate identification of vulnerable populations. This is where the precision part comes in.

In order to harness the power of big data, the Cancer Moonshot recommends the creation of a database called the Pre-Cancer Genome Atlas (PCGA). The idea for this big-data venture comes from The Cancer Genome Atlas (TCGA), an open project started in 2005 where scientists can assess molecular facts about individual (anonymized) patient tumors. The tumors in this database are often from patients in the late stages of cancer. Thus, the TCGA has greatly increased our understanding of how advanced tumors develop and respond to treatments but has provided little knowledge in how cancer starts. For that information, scientists need to see more than just a snapshot of tumors in the late stages.

The PCGA would give an earlier glimpse into cancer development by providing molecular data from a collection of pre-cancerous lesions and early stage tumors (think: colon polyps and precancerous skin moles). With data gleaned from the PCGA, a patient could enter a clinic with a pre-cancerous mole on her skin and a doctor could sequence the mole’s DNA to predict whether it is likely to progress to full-blown skin cancer. Scientists and doctors could also use PCGA data to identify new early cancer mutations, identify patients for clinical trials, and reduce the number of false positives during cancer screening. Gathering the human tissue for the PCGA will be a huge undertaking, but since the collaborations between large cancer centers have already been established via the TCGA, the task is achievable.

Another recommendation by the panel is to utilize genome-sequencing technology to identify cancer predispositions of individual patients. In other words, individuals may carry certain mutations that are not harmful under normal circumstances. When this same mutation is in the presence of additional environmental or genetic factors, it can lead to cancer more easily than if the mutation did not exist in the first place. Such mutations are known as cancer-predisposing mutations. They often run in families and are referred to as hereditary cancer syndromes.

With precision prevention, doctors aim to identify these syndromes in individual patients so as to develop an action plan to prevent cancer development long-term. Such an action plan may involve increased screening via colonoscopies or mammograms, strict adherence to lifestyle changes, or in some cases, surgeries to remove the organ of cancer interest. For example, Angelina Jolie famously underwent a double mastectomy after finding out that she carried the BRCA1 mutation, a hallmark of hereditary breast and ovarian cancer syndrome (HBOC). Combining a detailed family history with genetic testing in order to define a cancer prevention action plan is the ideal iteration of precision prevention in action [Figure 3]. Unlike precision medicine, precision prevention has the potential to stop cancer before it starts.

Figure 3: Precision Medicine vs. Precision Prevention. With Precision Medicine, cancer is initially detected in the patient and this patient’s tumor is then sequenced to find a cancer-causing mutation. Based on the results of this data, doctors can then prescribe a treatment regimen to specifically target the tumor. Even with this precise strategy, doctors and scientists can not completely predict the response of the tumor to the treatment. Tumors may stop, slow, or continue growing in response to the treatment over time. Precision Prevention starts when cancer is detected throughout a family tree. For example, if a patient’s aunt and grandmother died young from breast cancer, a doctor may recommend genetic testing of the patient prior to any signs of cancer. During this testing, a cancer predisposing mutation may be discovered which would then shunt the patient into a cancer prevention action plan (more frequent mammograms, healthy lifestyle, mastectomy surgery) to stop cancer before it starts.

One clear action item of the Cancer Moonshot is to determine the value of this prevention approach by identifying Lynch Syndrome (LS) in the general population via the Lynch Syndrome Demonstration Project. LS is a hereditary cancer syndrome that makes individuals more susceptible to the development of colon cancer. It is estimated that more than 1,000,000 people in the United States have LS and less than 5% are aware of it. In this project, patients presenting with colorectal cancer will be tested to determine whether they have LS. If they do have LS, the genetic testing will be extended to their family members. If these family members also have the syndrome, they can then be added to a national network of Lynch Syndrome patients for enhanced clinical trial enrollment and close monitoring via increased colonoscopies with the goal of preventing cancer before it starts.

These cancer prevention interventions may prove to drastically reduce cancer deaths or may have no effect whatsoever. Just because one has a hereditary cancer syndrome, does not mean that they will get the associated cancer. More research is needed to define the risk of cancer associated with certain mutations. Consequently, one of the key projects of precision prevention is to evaluate the success of such public health interventions to determine formal recommendations moving forward. As noted in the Cancer Moonshot report, precision prevention has the mandate to develop strategies that can truly be tailored to every individual, regardless of race, ethnicity, and socioeconomic status. Moving forward, it will be imperative to observe whether the interventions evaluated, the data collected, and the recommendations made are held to this high standard. Many of these same challenges are shared by the Precision Medicine Initiative so these lessons can be commonly learned across these two programs. But while precision medicine strategies show great promise to save patients who have already developed cancer, precision prevention is the clear path to save the population as a whole from the ravages of this horrible disease.

Steph Guerra is a PhD student working in the field of cancer research at Harvard Medical School and a former co-director of SITN.

Cover image: By Pete Souza (White House Flickr account) [Public domain], via Wikimedia Commons

For More Information:

Cancer Moonshot Blue Ribbon Report:

Hereditary Cancer Syndromes:

Cancer Screening:

NCI’s Take on Precision Prevention:

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