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The Cancer Miracle Isn’t a Cure.

It’s Prevention.

We cannot treat our way out of the rising cancer caseload. The only solution is a full-scale defense, so that nobody suffers the disease in the first place.

By Madeline Drexler
Illustrations by Stephanie Dalton Cowan

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In the next few years, cancer will become the leading cause of death in the United States. Later in this century, it is likely to be the top cause of death worldwide. The shift marks a dramatic epidemiological transition: the first time in history that cancer will reign as humankind’s number-one killer.

It’s a good news/bad news story. Cancer is primarily a disease of aging, and the dubiously good news is that we are living long enough to experience its ravages. Cancer’s new ranking also reflects public health’s impressive gains against infectious disease, which held the top spot until the last century, and against heart disease, the current number one.

The bad news is that cancer continues to bring pain and sorrow wherever it strikes. Siddhartha Mukherjee titled his magisterial biography of cancer The Emperor of All Maladies, quoting a 19th-century surgeon. He left out the second part of the surgeon’s epithet: “the king of terrors.” Modern targeted treatments and immunotherapy have in some cases led to wondrous cures, and many malignancies are now caught early enough so that their sufferers can live out full lives. But advances in treatment alone will never be enough to fully stem the burden of cancer.

As every public health professional knows, on a population level, the only way to substantially reduce incidence and mortality for any disease is through prevention. And on a broad scale, we have made far less progress preventing cancer than preventing its predecessor scourges. We tamed infections with sanitation and vaccines, abetted by antibiotics. We tamed heart disease through smoking cessation, better medical management of risk factors such as high cholesterol, and improved interventions for a condition that has clear points of intervention and responds more readily to lifestyle changes.

Cancer is a different story. Even today, it continues to occupy our collective imagination as the king of terrors: insidious, capricious, relentless. Anyone who has suffered cancer, or has suffered alongside a loved one with the disease—a considerable portion of the population, given that more than one in three of us will be diagnosed with a malignancy during our lifetime—knows the anguish and helplessness that trail the diagnosis.

In 2015, a study in Science seemed to confirm our primal fear. It argued that only one-third of the variation in cancer risk in tissues is due to environmental assaults or inherited genetic predispositions. The majority of risk, the researchers concluded, was due to “bad luck”—random mutations during normal DNA replication.

And though that study provoked torrents of criticism about whether its conclusions based on tissue studies could be spun up to populations, it’s true that cancer is the price we pay as organisms composed of trillions of cells. Cell division is an imperfect process; like a biological keyboard with a letter missing, it makes mistakes. For that reason, it is unlikely that cancer could ever be eradicated.

The reality of cancer lies somewhere between the public health ideal of perfect prevention and the depressing stochastics of bad luck. Current research suggests that at least half of cancer cases—estimates range from 30 percent to upward of 70 percent—could be prevented by applying what we already know. The other half of cancer cases—including the elusive and often deadly types often caught too late to make a difference, such as ovarian, pancreatic, and brain tumors—could be detected and potentially even prevented far earlier if basic science and promising diagnostic technologies received the sustained government support they need.

Put simply, cancer must be framed not just as a curable disease but equally as a preventable one. “We will always need good treatments,” says Timothy Rebbeck, the Vincent L. Gregory, Jr. Professor of Cancer Prevention at the Harvard T.H. Chan School of Public Health and Dana-Farber Cancer Institute, and director of the School’s Zhu Family Center for Global Cancer Prevention. “But we can’t treat our way out of this problem. In order to make a dent in a public health sense, we must prevent cancer.”

A Grim Tally

In 2019, according to the American Cancer Society, an estimated 1,762,450 people will be diagnosed with cancer in the United States and an estimated 606,880 will die of the disease. Globally, cancer killed an estimated 9.6 million people in 2018—more than malaria, tuberculosis, and HIV combined. In this century, cancer will become not only the leading cause of death worldwide (in 91 nations it already ranks as the first or second cause of death before age 70, according to the World Health Organization) but also the single biggest hurdle to boosting life expectancy in scores of nations.

The reasons for cancer’s ascendancy are complex. Part of the trend is demographic: The human population is both growing and aging each year, meaning more people are vulnerable to the disease, which takes advantage of the waning immune system and the accumulated DNA damage that accompanies aging. But cancer’s chief risk factors are also changing. While smoking is down in the United States, for example, it is up in Africa and the Eastern Mediterranean, as tobacco companies expand into new markets. And while cigarette use is the most important risk factor for cancer worldwide, cancer-causing infections, such as hepatitis and the human papilloma virus (HPV)—both preventable with vaccines—account for up to 25 percent of cancer cases in some low- and middle-income countries.

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Current research suggests that at least half of cancer cases could be prevented by applying what we already know.

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These shifting sands of causation are also evident in the United States. Over the past 25 years, while cancer deaths have risen in number as the population grows, the cancer death rate has steadily declined. As of 2016, the cancer mortality rate for men and women combined had fallen 27 percent from its peak in 1991. The engine behind this impressive public health feat was the decline in smoking, though early detection and improved treatments also played a role. In 1965, 42 percent of U.S. adults were cigarette smokers; in 2017, just 14 percent. Lung cancer death rates declined in tandem, falling 48 percent from 1990 to 2016 among men and 23 percent from 2002 to 2016 among women.

That public health victory is now in peril. In the next five to 10 years, experts say, the cancer-causing effects of obesity could actually reverse the downward trend ushered in by the decline in smoking. Indeed, obesity could soon become the number-one risk factor for cancer in the United States and eventually around the world. And given obesity’s seeming irreversibility, thwarting cancer’s concomitant rise will be exceedingly difficult. In the U.S., 39.5 percent of adults are now estimated to be obese and an additional 31.8 percent overweight.

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The Zhu Family Center for Global Cancer Prevention

In February 2019, the Harvard T.H. Chan School of Public Health established the Zhu Family Center for Global Cancer Prevention, an innovative interdisciplinary center that will focus on education and research aimed at preventing people from getting cancer and improving early detection. Unlike most current cancer-prevention research, which takes place in siloed disciplines that seldom communicate or join forces, the Zhu Family Center will encourage partnerships among researchers exploring the basic causes of cancer, those who build technologies that can be used to detect cancer early, and those trained to implement those strategies in local communities.

The center’s director is Timothy Rebbeck, the Vincent L. Gregory, Jr. Professor of Cancer Prevention at the Harvard Chan School and Dana-Farber Cancer Institute (DFCI), professor of medical oncology at DFCI, and associate director for equity and engagement at the Dana-Farber/Harvard Cancer Center. Rebbeck leads molecular epidemiology studies of cancer etiology, outcomes, health disparities, and global health. His work has led to insights into the genetic and environmental causes of breast, prostate, skin, endometrial, and ovarian cancers.

“We hope to create a new niche in the cancer- prevention field,” says Rebbeck, “finding areas that are not wholly technology and not wholly public health, but the interface of these different realms. That’s where we think we can make an impact.”

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Obesity is a well-established risk factor for at least 13 cancers. According to a 2019 report in The Lancet Public Health, excess body weight in the U.S. accounted for up to 60 percent of all endometrial cancers, 36 percent of gallbladder cancers, 33 percent of kidney cancers, 17 percent of pancreatic cancers, and 11 percent of multiple myelomas in 2014.

Increasing obesity among younger people may portend a bigger wave of cancer in the near future, according to the The Lancet Public Health study. In the U.S., the incidence significantly increased for six obesity-related cancers in young adults, with each successively younger generation suffering a higher rate of cancer than the previous generation. These cancer cases serve as sentinels for future disease in older people. In light of rising rates of colorectal cancer among young adults, a trend suggesting environmental factors, the American Cancer Society last year lowered its recommended age for people’s first cancer screening, from 50 to 45.

Calculating the Benefits of Prevention

Two kinds of prevention can substantially reduce cancer deaths. The first, and most important, is primary prevention: averting a malignancy by attacking its causes and promoting the factors that protect against it. Taxes on cigarettes and alcohol, vaccination against cancer-causing pathogens such as HPV and hepatitis B, promoting healthy eating and regular exercise: All are examples of primary prevention. Primary prevention works when social and economic conditions, the built environment, and the public health and medical systems work in concert to support it.

Secondary prevention controls cancer by screening to detect the disease at its earliest stages and, if necessary, intervening early in the course of the disease’s progression. Secondary prevention has helped bring down death rates of breast, cervical, and colorectal cancers, among others.

Long-term epidemiological studies have clarified which cancers are preventable and by how much, if specific risk factors were reduced. A 2016 report in JAMA Oncology by the Harvard Chan School’s Ed Giovannucci, professor of nutrition and epidemiology, and Minyang Song, assistant professor of clinical epidemiology and nutrition, found that 20–40 percent of cancer cases and about half of cancer deaths could potentially be prevented through lifestyle modification, including quitting smoking, avoiding heavy alcohol drinking, maintaining a body mass index of 18.5 to 27.5, and exercising at moderate intensity for at least 150 minutes or at a vigorous intensity for at least 75 minutes every week. (An additional bonus is that promoting cancer’s protective risk factors could also prevent other common noncommunicable diseases, such as type 2 diabetes, heart disease, dementia, and depression.)

A 2018 study in Science—co-authored by Song, Giovannucci, and Harvard Chan’s Walter Willett, professor of epidemiology and nutrition—made an even more emphatic case for prevention. It noted that for cancers in which most of the driving genetic mutations are caused by the environment—such as lung cancers, melanomas, and cervical cancers—85 to 100 percent of new cases could be eliminated through smoking cessation, avoidance of ultraviolet radiation exposures, and vaccination against HPV, respectively.

“With such further research, we envision that cancer death rates could be reduced by 70 percent around the world, even without the development of any new therapies,” the authors concluded. “Such a reduction, similar to that for heart disease over the past six decades, will only come about if research priorities are changed.” Specifically, the authors argue for more support of molecular, behavioral, and policy research on prevention.

Even individuals at high inherited genetic risk for cancer can benefit from lifestyle change, adds Peter Kraft, professor of epidemiology at the Harvard Chan School. In 2016, Kraft published a paper in JAMA Oncology showing that U.S. women who were in the highest decile of breast cancer risk because of factors they could not alter—mostly genetics but also family history, height, and menstrual and/or reproductive history—actually benefited the most from a healthy lifestyle. In fact, the women who had the highest nonmodifiable risk but also kept their weight down, did not drink or smoke, and did not use menopausal hormone therapy had about the same breast cancer risk as an average woman in the general population.

“Although our day jobs are studying the genetics of cancer, genetics is not destiny, by any means,” says Kraft. “This is something we’ve seen consistently across many cancers—and many diseases generally. Even if you’re high-risk based on your genetics, there’s still plenty that you can do to reduce your risk. In fact, high-risk individuals are the people who seem to reap the biggest benefit from adopting healthy lifestyles.”

Cancer Clues across Two Dimensions

Should anyone still doubt that many cancers are preventable, the inarguable proof is how the disease plays out over time and space. Cancer rates and types can starkly change within a country and starkly vary between countries. These variations are not genetic—a small minority of cancers are directly attributable to known, death-dealing DNA mutations. Rather, they reflect external—and, in principle, modifiable—risk factors.

For example, lung cancer eclipsed all other cancers during most of the 20th century in the United States because per capita cigarette consumption shot up from 54 cigarettes a year in 1900 to 4,345 cigarettes in 1963, then fell to 2,261 in 1998. The initial upward trend was powered by corporate profiteering. The downward slope was powered by the landmark 1964 U.S. Surgeon General’s report on smoking and health, which firmly linked smoking and lung cancer and led to public education, indoor smoking bans, and higher tobacco taxes. Another instance of a breathtaking prevention success within a country took place in the 1980s and 1990s in Taiwan, which saw an 80 percent decline in liver cancer rates in birth cohorts that received hepatitis B vaccination early in life. (The most common causes of liver cancer are infection with the hepatitis B virus in Africa and East Asia, and the hepatitis C virus in the U.S. and Europe.) And Australia recently reported it is on course to completely eliminate cervical cancer in the coming decades through vaccinations.

The spatial dimension of cancer is equally revealing. When racial or ethnic groups migrate from one part of the world to another, their cancer risks quickly take on the local patterns. Between 1975 and 2003, for example, numerous studies looked at cancer incidence in U.S. Caucasians, immigrant groups, and matched controls. Among the populations studied were first- and second-generation Japanese immigrants, Asian American women, Vietnamese Americans, and Hmong refugees from Vietnam, Laos, and Thailand. Drawing on data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program, the studies found that the kinds of cancers that were newly diagnosed among first-generation immigrants in the U.S. were nearly identical to the kinds in their native countries. But over subsequent generations, their cancer patterns became distinctly American. This was especially true for cancers related to hormones, such as breast, prostate, and ovarian cancers, and to cancers attributable to Westernized diets, such as colorectal malignancies.

Understanding Cancer’s Genesis

Given the fact that many cancers can be averted, what would it take to make the dream of prevention a reality?

First, scientists say, we must understand the earliest biological events that give rise to the birth of a cancer cell. While genomic analyses have provided a good molecular description of cancer, researchers still don’t understand how and when cells start to go rogue.

“Cancer initiation is much less well understood than the biology of cancer cells themselves,” says Brendan Manning, professor of genetics and complex diseases at the Harvard Chan School. “Cancer cells are doing things that normal cells do, only in an uncontrolled manner. So, how is cancer initiated? What are the brakes on early cancer? What are the challenges that the cancer cell faces in becoming a cancer cell? How does the cancer cell remove enough of those brakes so that it will become malignant?” Answering those questions will also shed light on the mechanisms by which apparent cancer risk factors, such as aging or obesity or chronic inflammation, trigger uncontrolled cell growth and progression to cancer, says Manning.

Manning’s lab explores how the body’s cells and tissues sense nutrient shifts in their local environment and adapt accordingly. “The cells in our body have the ability to acclimate to changes in nutrient availability, and this is achieved through special lines of communication—referred to as nutrient sensing pathways—that serve to tune cell metabolism to match these changes,” he says. “Understanding these fundamental mechanisms has provided us with key insights into how nutrient sensing becomes corrupted in human cancers, which universally exhibit alterations in cellular metabolism that underlie uncontrolled growth.”

Another biological unknown is the role of the microbiome—the trillions of microbes in and on our bodies—in human cancer. “These living organisms can at times be found right at the site of the cancer,” says Wendy Garrett, professor of immunology and infectious diseases at the Harvard Chan School. “We are beginning to see very provocative associations between the microbiome and cancer, and interesting molecular mechanisms—which are emerging from experiments with cells and in tissue cultures and preclinical mouse models—may explain these associations.”

One intriguing culprit on which Garrett and her colleagues are focusing is Fusobacterium nucleatum, normally a microbial denizen of the mouth. Garrett’s lab and others have shown that the bacterium is abundant in colon tumors. She wants to find out why, whether such bacteria are important early signals for carcinogenesis, and if any interventions—such as changing one’s everyday behaviors and exposures, including diet and tobacco use—map onto the microbiome and could potentially halt the disease process.

The microbiome is proving to be a vast and inviting landscape in cancer biology. In humans, gum disease caused by bacterial infections has been connected to higher risk of pancreatic cancer. In mice, lung tumors appear to alter nearby bacterial populations to help the tumors thrive—and antibiotics appear to shrink the tumors. Experiments in mice have even linked a disrupted gut microbiome to greater risk of invasive breast cancer.

“It’s possible that the cancers for which we currently don’t fully understand risk factors—such as pancreatic and ovarian cancer—might be tied to infections and therefore be preventable,” says Giovannucci. “Forty years ago, we didn’t know what caused stomach cancer. Now we know: the bacterium Helicobacter pylori.” H. pylori is treatable with antibiotics, and stomach cancer rates have dropped considerably as a result.

Prevention via Detection

With many tumors, there is a lag time of 20 years or more between the development of the first cancer cell and the onset of end-stage metastatic disease. Knowing each cancer’s basic biology could lead to a host of new technologies that register early biomarkers of the disease, potentially opening up new ways to head off malignancy before it spreads. That prospect would be transformative for the implacable cancers that don’t cause symptoms until they have reached their late and often incurable stages.

Among these promising biomarkers are proteins that signal early tumors, DNA or RNA, small molecules, circulating tumor cells, immune cells, and other infinitesimal biological entities. Scientists are also fashioning synthetically engineered biomarkers that harness the body’s own biology to spin off early signals of disease. “It’s a matter of screening technology getting refined enough so that you can find two suspicious molecules in four liters of blood which suggest you are at risk for or have already developed cancer,” says Rebbeck.

Sangeeta Bhatia, a biomedical researcher and early-detection pioneer, and the John J. and Dorothy Wilson Professor of Engineering at the Massachusetts Institute of Technology, injects nanoparticles into the bloodstream that respond to cancer-associated enzymes. When the particles find the enzyme for which they are designed, a chemical reaction produces “reporters”: synthetic chemicals eliminated in the urine that can tip off researchers to a nascent malignancy. Her lab is searching for highly specific biomarkers for often-elusive tumors of the ovary and lung and in colon metastasis. Clinical trials for the technology will begin later this year.

“Ultimately, we’d like to be in a place where you could do a urine test on a paper strip for a defined set of cancers,” Bhatia says. Other scientists envision, in the more distant future, continuous monitoring of cancer risk through smart toilets, wearables such as diagnostic imaging bras, and other passive and noninvasive technologies.

In clinical medicine, the value of screening tests is gauged by their sensitivity and specificity. Sensitivity measures a test’s ability to identify people who have the condition that is being tested for; a highly sensitive test will not generate false-negative results. Specificity measures a test’s ability to identify people who do not have the condition that is being tested for; a highly specific test will not generate false-positive results.

All the futuristic approaches described above require knowing that a technology’s molecular quarry is made by a certain kind of cancer cell and only that cancer cell—that is, the screening test must be highly specific. Since many tiny malignancies never go on to become metastatic disease—because the immune system reins in such cells—the ideal biomarker would not only tip off doctors to the presence of a cancer or precancer but also predict whether the suspect cells are aggressive or slow-growing. “[O]ne can imagine a day when healthy individuals are routinely tested for these biomarkers to detect early cancers, along with lipid concentrations to detect early cardiac disease, at periodic visits to their physicians,” the Harvard Chan School scientists wrote in Science in 2018.

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While genomic analyses have provided a good molecular description of cancer, researchers still don’t understand how and when cells start to go rogue.

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Before liquid biopsies, “smart tattoos” that light up in the presence of cancer cells, small ingestibles that monitor the gastrointestinal tract, and other early-detection tests that sample blood, urine, saliva, or the breath can ever become part of the annual physical, they will have to be honed to the point of 99.9 percent accuracy or higher, similar to the accuracy of the early-pregnancy urine tests available at any drugstore. That is, they must be both highly sensitive and highly specific. This high degree of accuracy prevents false negative or false positive results when the test is used in large numbers of people.

Such tests could also help doctors decide whom to monitor more closely for cancer. “Advances in biomarker testing could help us better risk-stratify the population,” says Jane Kim, professor of health decision science at the Harvard Chan School. “The whole point of screening is to pull out the people who are at lowest risk and focus your attention on those at highest risk. Today, with cervical and even colorectal cancer, there is a prevention mechanism: You remove precancerous lesions before they develop into cancer. But with breast cancer, you need early detection, because there are no really strong prevention mechanisms. Risk-stratifying patients would help efficiently identify high-risk patients through prevention and early detection.”

Validating today’s candidate biomarkers will partly depend on long-term cohort studies—such as the Nurses’ Health Study—that have followed healthy volunteers over decades, collected biological material from these volunteers, and tracked the natural course of diseases as the participants aged. To speed the clinical validation of such early diagnostic tests, researchers will first try them out on people at high genetic risk for various cancers, for whom the tests have a higher likelihood of detecting an abnormality and making an impact.

“Combining basic science and cohort studies would also facilitate the discovery and validation of new biomarkers,” says Manning. “If you’re banking molecular information from blood and tissue, and the data changes over time, you can look back retrospectively at thousands of patient outcomes and see if the changes predicted an outcome or might be related to that outcome. Basic science holds the key to determining how that identified biomarker links back to the disease state and whether it is contributing to the disease’s onset—perhaps as a risk factor—or is a consequence of the disease.”

But being able to find an early cancer or predict its progression is not enough. “The key thing is that you have an intervention and that it’s actionable,” says Rebbeck. Such interventions might include surgery, cancer vaccines, anti-inflammatory drugs, a standard chemoprevention treatment, tinkering with the body’s microbiome, or even lifestyle change. “If you detect an early cancer biomarker but cannot act on it, then it may just produce anxiety,” he says. “There is a quote from Sophocles that we sometimes use: ‘Knowledge is but sorrow when wisdom profits not.’”

From Science to Action

Just as crucial will be translating new scientific insights into public health practice—a field known as implementation science. “Public health impact is efficacy times reach,” says Karen Emmons, professor of social and behavioral sciences at the Harvard Chan School. “We often develop interventions without thinking about the end users and what could get in the way of true impact, so shame on us as a field. As a scientific community, we think, rather arrogantly, ‘Well, we’ve shown that colorectal cancer screening is important—why don’t community health centers just make sure that everybody has colorectal cancer screening? It’s clear that vaccines are important—why aren’t all kids getting HPV vaccine?’ But the real question is: How do you structure systems to make those goals possible?”

Today’s cancer prevention and detection efforts regularly fall short in their impact. Although HPV vaccination administered in preadolescence, before a teen becomes sexually active, theoretically prevents some 90 percent of cervical cancers, the U.S. vaccination rate among adolescents is low. In 2017, only 42 percent of girls and 31 percent of boys received the two recommended doses before their 13th birthday. Similarly, in 2015, only 50 percent of women ages 40 years and older reported having a mammogram within the previous year, and only 64 percent within the previous two years.

Even the most well-established intervention against the most formidable cancer threat in the U.S.—lung cancer—is only fitfully used. “For some time after we started doing lung cancer screening for smokers, we didn’t also do smoking cessation with them,” says Emmons. “Even today, we still do it inconsistently. Now how stupid is that?”

Alan Geller, senior lecturer on social and behavioral sciences at the Harvard Chan School, has seen up close how the failure to translate science into action and policy leads to health disparities. “All of my work now is trying to ask the big question of who unnecessarily dies from preventable diseases,” he says. “Smoking rates are at best stabilizing among low-income people in the U.S.—but they’re stabilizing at 30 to 33 percent of the adult population. Among the well-to-do, smoking rates have for years been well below 10 percent. It’s not a racial disparity—it’s an income disparity, because the smoking rate among whites and African Americans is exactly the same. So we should target low-income people. Public health needs to go where high-risk people are.”

Geller adds that with smoking, four strategies could substantially reduce cancer deaths. “First would be to work really hard in the U.S. South, where smoking rates are double those in the North. Second would be working among people with mental health issues, because 41 percent of all smokers have diagnosed mental health conditions. Third would be figuring out how we could intervene with people who have GEDs [general education diplomas, also known as high school equivalency certificates]; 14 million people in the United States have one, and as a group their smoking rates are 40 percent. And fourth would be working with people in public housing—figuring out how their doctors and housing providers can give them access to nicotine replacement therapy, which is extraordinarily inexpensive, and how they can use community health workers and patient navigators. Those are all beautiful, low-cost, public health models for smoking cessation and lung cancer prevention.”

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“When you look at cancers that are preventable, as soon as something comes online to screen or prevent, you start to get pretty sharp disparities by race, ethnicity, and income.”

—Karen Emmons, professor of social and behavioral sciences

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It’s almost a public health truism that when breakthrough medical advances hit the market, they disproportionately benefit people of means and thus widen health disparities. This divide is brutally apparent with cancer. From 2012 to 2016, for example, death rates in the poorest U.S. counties were two times higher for cervical cancer and 40 percent higher for male lung and liver cancers compared with rates in the richest counties. Poverty is also linked with lower rates of routine cancer screening, later stage at diagnosis, and a lower likelihood of receiving the best treatment.

“There are still parts of this nation where the rates of cervical cancer mirror those in developing countries—not developed countries,” notes Susan Curry, distinguished professor of health management and policy and dean emerita of the College of Public Health at the University of Iowa, and immediate past chair of the U.S. Preventive Services Task Force. “Are there barriers to screening within the population eligible to be screened? Are there barriers in terms of the organization and availability of screening? Are there barriers in terms of, you can get screened, but if you don’t have the means to follow up on a positive test or don’t understand what that is, then screening is for naught? We can pinpoint some pretty disturbing disparities. But how much are we investing in the intervention science that we need to close those gaps?”

These divergences are writ larger on the global stage. Earlier this year, The Lancet Global Health published a damningly titled article: “Cervical cancer: lessons learned from neglected tropical diseases.” The malignancy claims 310,000 lives annually around the globe, making it the fourth-most-common cancer killer of women. “[C]ervical cancer is not a disease of the past—it is a disease of the poor,” the authors state. They go on to list the hurdles that cervical cancer—which could virtually be eliminated from the planet with vaccination and screening—shares with neglected tropical diseases: Both accompany poverty; strike populations mostly overlooked by policymakers; are associated with stigma and discrimination; strongly affect female morbidity and mortality; tend to be neglected in clinical research and technological development; and can be controlled, prevented, and conceivably eliminated through currently available solutions that are cheap and effective.

It’s worth noting that in Africa, more people die from cancer than from malaria. And while overall cancer death rates have been rising in Africa—and will double in the next 20 years—malaria death rates are dropping because of concerted efforts to prevent and treat the infection.

A 2009 study in the journal Cancer Epidemiology, Biomarkers & Prevention underscored the fact that the newest and best cancer preventions disproportionately benefit people of means. The study found that the more knowledge, technology, and effective medical interventions there are for a given disease—that is, the more amenable a disease is to early detection and cure—the wider its disparities, because people who have knowledge, income, and useful social relations stand a better chance of surviving. By contrast, with diseases where effective medical interventions are absent or negligible, such as ovarian or pancreatic cancers, social and economic resources are of limited use, and survival differences between the most and least socially advantaged people are minimal.

“When you look at cancers that are preventable, as soon as something comes online to screen or prevent, you start to get pretty sharp disparities by race, ethnicity, and income,” says Emmons. “Colon cancer is a great example. Before sigmoidoscopy and colonoscopy screening came on board, there were actually slightly higher rates of colon cancer in whites than there were in blacks. Literally within three years after these screening tools were introduced, colon cancer rates among whites fell dramatically, but the rates in blacks did not. You see this over and over again.”

Such health inequities represent lives lost to cancer. When Emmons looks at new technologies, she asks: “What is the user perspective? How will the new technology interface with places where lower-income populations get their care? What does the technology mean for population health management, as opposed to managing the health of an individual? If you don’t pay attention to how these technologies are utilized across racial and economic lines, you wind up with persistent disparities that we shouldn’t tolerate.”

The Prevention Mindset

In the 1970s, a New Yorker cartoon depicted two stereotypical (for that era) male scientists standing before a blackboard scrawled with complicated equations. In the middle of these obscure scribbles is the phrase: “THEN A MIRACLE OCCURS….”

So it goes with cancer. “A cure for cancer” is our cultural synonym for a miracle. But as Curry points out, “We’re still waiting for that miracle.” When cancer treatments work, as they increasingly do, they seem indeed miraculous. But often, they come too late. The real miracle would be to prevent cancer from ever striking.

“Prevention is very hard,” Rebbeck concedes. “People want to think about cure. They say we need to cure cancer—and if someone has cancer, you absolutely want to cure it. But what’s not gotten into the public mindset is that we need to prevent cancer so that nobody needs to be cured.”

“For decades, success in cancer control has been ‘just around the corner,’” wrote Tom Frieden, the then-commissioner of the New York City Department of Health and Mental Hygiene, in 2008 in The Oncologist. Frieden, who went on to lead the U.S. Centers for Disease Control and Prevention (CDC), added, “Yet, to wage a true war on cancer, we must expand our approach to give preventive interventions at least as much focus as medical treatment.” Pointedly, he added that such a goal would require correcting the imbalance between “money invested in cancer treatment and money invested in cancer prevention.”

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In the next five to 10 years, the cancer-causing effects of obesity could reverse the downward trend ushered in by the decline in smoking.

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Currently, those two streams of funding are wildly unequal. In fiscal year 2018, the last year for which data is available, only 5.7 percent of the National Cancer Institute (NCI) budget was allotted to cancer prevention and control. Today, even the money for treatment research and other programs may be whittled back. The proposed fiscal year 2020 budget for the NCI is $5.2 billion—nearly $900 million less than the enacted 2019 budget. At the CDC, the proposed budget for cancer prevention and control was trimmed by more than $34 million—a 9 percent cut from last year. Globally, cancer prevention research is allotted an estimated 2 to 9 percent of global cancer research funding.

“The biggest unknown in cancer prevention is how to sustain proven, effective, and lifesaving preventive efforts over the long run,” says Howard Koh, the Harvey V. Fineberg Professor of the Practice of Public Health Leadership at the Harvard Chan School and the Harvard Kennedy School; former assistant secretary for health for the U.S. Department of Health and Human Services; and former commissioner of public health for the Commonwealth of Massachusetts. “Prevention should be integral, not optional. But in government, prevention budgets are always the first items to be cut and the last to be restored.”

Some researchers go so far as to argue that government research funding should be shifted somewhat from treatment to prevention—because solving the front end of the problem will save countless more lives. Others disagree, arguing that cancer will never go away completely and that, even today, we only know how to prevent about half of cancer cases. “You can take the pie and divide it differently or increase the pie,” says Curry. She would like to see more support for front-line public health. “Clearly, we need more dissemination science. There’s a huge gap between what we know and what we do.”

Manning insists that bench science is just as important in prevention. “In most cases, the biggest breakthroughs in biomedical research, including cancer biology, are made using reductionist approaches in which you’re isolating one aspect of the broader biology,” he says. “Stripping a biological problem down to its essence is key. We need to keep funding research that allows us to understand with detail and accuracy the aspects of biology that are important for cancer initiation. But right now, there is an overemphasis at the NIH [National Institutes of Health] and at NCI on supporting research that purports to be directly translatable or is seemingly translatable to treatment for an existing cancer, rather than on understanding how cancer begins.”

Shoe-leather population research and high-tech bench science: Both will be needed to stop cancer’s unabated rise.

Shaping Public Opinion

Desperate entreaties for increased support of cancer prevention are nothing new. In 1929, James Ewing, the director of cancer research at Memorial Hospital in New York City, wrote in Public Health Reports: “It is only within the last few years that cancer has been considered a public health problem. I suppose that the old attitude was due to the fact that cancer is not an infectious disease; also largely because of the popular notion that it is not preventable; and probably also, to a large extent, to the feeling, fairly well grounded, that the disease is incurable.” Ewing hoped for a change in public attitudes. “[C]ancer is a public health problem of the first importance, because many of the forms of cancer are preventable, and if the public were thoroughly informed, a definite reduction in the incidence of cancer might follow.”

Ninety years later, most people still do not grasp that point. Nor do they see that with robust research, the incidence of today’s more elusive and frightening cancers could also fall. In the 2017 American Institute for Cancer Research’s Cancer Risk Awareness Survey, for example, fewer than half of Americans recognized that alcohol, processed meat, high amounts of red meat, low amounts of fruits and vegetables, and not enough physical activity all have clear links to cancer development. And contradicting scientific evidence, they tended to blame cancer on factors they couldn’t control rather than on those they could. Nuclear power ranked eighth as a perceived cause of cancer, for example, and food additives ninth. Obesity—which may soon become the top modifiable risk factor for cancer—ranked 16th.

As Frieden explained in 2008 in The Oncologist, cancer-causing agents “are not primarily trace chemicals found in food, water, or air, but instead are the major constituents of what humans consume voluntarily. These agents are best viewed as toxins, and public policies can substantially reduce our exposure to them.”

A Moon Shot for Prevention

In 1969, the Citizens Committee for the Conquest of Cancer, inspired by the success that year of the Apollo 11 space mission and propelled by the indomitable philanthropist Mary Lasker, conceived of a “moon shot” for cancer. That December, the group ran a full-page ad in The Washington Post and The New York Times: “Mr. Nixon: You can cure cancer.” At the time, a cure was perceived to be imminent.

President Richard Nixon’s grandiloquent response in his 1971 State of the Union address: “The time has come in America when the same kind of concentrated effort that split the atom and took man to the moon should be turned toward conquering this dread disease. Let us make a total national commitment to achieve this goal.”

But the War on Cancer, as the moon shot was called, didn’t reach its goal. Partly, that was because “cure” was an erroneous target. Cancer is not one disease, but more than 200. “We talk about a ‘cure’ for cancer, but no one would ever use the term ‘cure’ for infectious disease—they would talk about a cure for AIDS or TB or malaria,” says the Harvard Chan School’s Giovannucci. “You have to think about these diseases one by one.” More fundamentally, the War on Cancer failed because it spent far too little on cancer prevention and cancer prevention research.

There are many reasons why prevention research is unenticing. Most societies are reactive, not proactive. The final phases of research on treatment are simpler than research on prevention. Curing a patient with advanced disease is more dramatic than preventing disease in a healthy person. And perhaps most conspicuously, treatments earn far higher profits than do new diagnostics or prevention measures.

Yet every great public health success has overcome those entrenched obstacles. “The way I message this to lawmakers is that our well-being is a gift; we can’t take good health for granted, and prevention is a powerful way to protect that gift. When prevention works, you can enjoy the miracle of a perfectly normal, healthy day,” says Koh. “When I interact with lawmakers, I often ask about whether they have experienced the pain of losing a loved one when it could have been prevented. That usually humanizes the conversation and gives it relevance and immediacy.”

A cure for cancer is our culture’s threadbare metaphor for a miracle. But a cancer prevented is even better than a cancer cured. When cancer becomes our leading cause of death—as it soon will—cancer prevention will become our leading cause of life.

Madeline Drexler is editor of Harvard Public Health.