• 2008 Fall/Winter Paths of Progress

    What is a Cure?

    As our knowledge of cancer grows, our vocabulary for dealing with the disease grows with it.
    By Richard Saltus

    graphThirty years ago, half of cancer patients survived five years or more; today, the rate is more than two-thirds. 

    Not so long ago, cancer was so feared that many dared not say its name: "The Big C," they called it. These days, people speak much more openly and the disease has lost some of its stigma and death-sentence aura. Treatments are better, mortality rates are falling, and incidence rates for some forms of cancer are declining.

    Now another "C" word bubbles up often in the cancer community – "the cure." It's hardly a new word, of course: A "cure for cancer" has long been near the top of humankind's wish list. The earliest documented case of cancer, recorded on papyrus in about 1,500 BC in Egypt, was treated by burning with a hot iron. The ancient physicians opined that the disease was not curable. But with the explosion of knowledge about cancer beginning in the mid-20th century, optimism surged. In the 1970s, for example, the American Cancer Society (ACS) used a slogan, "We want to wipe out cancer in your lifetime."

    Today, "For the Cure" is a frequent rallying cry in the names of organizations and fundraising events. At Dana-Farber and other cancer centers, health care providers will tell you that being part of this mission is what brings them to work every day.

    After all, the reasoning goes, science and technology have defeated polio and smallpox, sent people to the moon, unlocked the code of the human genome. Why should biomedicine not eradicate the scourge of cancer?

    But with increasing knowledge of cancer's many faces and its ability to outwit medical attacks, the definition of the term "cure" grows more ambiguous. As researchers delve ever deeper into the genetic jungle of the cancer cell, their vision of an outright cure – especially a single, cancer-eliminating solution – is giving way to other "c" words, such as conquer, control, and making cancer a chronic disease: a successful long-term campaign rather than a knockout blow.

    "Cure is a word that I don't use a great deal; it is promising something that may or may not be possible," says Robert J. Mayer, MD, a senior cancer researcher at Dana-Farber and physician at Dana-Farber/Brigham and Women's Cancer Center. "Instead I say to patients, 'You will be alive and well, and in 20 years we'll look back at this and have a chuckle.'"

    "People tend to forget where we were and where we are now – our progress is incremental, but our progress is real."
    – Len Lichtenfeld, MD  

    Certainly, some cancers can be cured today, and others will be in the future. Cancer is an umbrella term for several hundred different diseases all caused by damaged DNA that spurs cells to grow uncontrollably, invade tissues and organs, and spread menacingly to distant parts of the body. Further complicating matters, cancer cells aren't derailed by a lone defect, but often have an array of abnormalities that enable them to survive the body's cellular self-destruct mechanisms. They are also quite adept at evading even the most powerful and toxic cancer drugs. Few scientists today envision one all-powerful key that would solve the puzzle.

    "Will we have the magic bullet that will cure all cancer? The answer is no, but we will increasingly be able to keep this disease under control – people will live a long time with it," says Len Lichtenfeld, MD, deputy chief medical officer for the ACS. "People tend to forget where we were and where we are now – our progress is incremental, but our progress is real."

    Realistic goals

    Except for surgical removal and occasionally successful radiation therapy, no reliably effective cancer treatments existed until the late 1940s, when DFCI founder Sidney Farber, MD, achieved the first (though initially very temporary) remissions in childhood leukemia with the forerunners of today's chemotherapy drugs. The opening of the chemotherapy era inspired a surge of optimism and successful lobbying for government funding. In 1957, an official of the National Cancer Institute declared: "The next step – the complete cure – is almost sure to follow."

    Farber himself was bullish, believing that a cure was on the horizon, "lacking only the will and the kind of money and comprehensive planning that went into putting a man on the moon," as he was quoted in a New York Times full-page ad calling on then-President Nixon to wage an all-out "War on Cancer." Intense lobbying by Farber and other physicians and by citizen activists led to Nixon's 1971 National Cancer Act, which provided record-high funding for cancer research but at the same time raised unrealistic expectations.

    Nearly 30 years later, in 1998, the ACS issued a more modest challenge to the cancer community: Between 1992 and 2015, it hoped to see "a 50 percent reduction in age-adjusted cancer mortality rates; a 25 percent reduction in age-adjusted cancer incidence rates; and a measurable improvement in quality of life (physical, psychological, social, and spiritual) from the time of diagnosis and for the balance of life of all cancer survivors."

    In 2007, the ACS reported that despite progress, it was unlikely those goals would be achieved without "substantial breakthroughs" in early detection or treatment. As of 2004, cancer incidence rates had dropped 10.2 percent since 1992 – less than half of what would be necessary to meet the 25 percent incidence reduction goal by 2015.

    Cancer death rates also declined between 1992 and 2004, but at a pace that is estimated to reduce deaths by about 38 percent by 2015, rather than the hoped-for reduction of 50 percent.

    Dana-Farber has set a goal "of conquering at least one major form of cancer within a decade." The goal, explains President Edward J. Benz Jr., MD, is not necessarily a complete cure.

    "Many people think that cancer is like polio, that there will be a picture of a vial of something in the newspaper and [the disease] is gone," he says. "That's what we'd like cancer to be – something our grandchildren won't even remember."

    However, says Benz, "The reality is that most cancers will be managed rather than eliminated, and people will be able to live with them and deal with them. Except for some infectious diseases that we cure with antibiotics, there are almost no diseases where we take them away and they never come back again."

    Redefining progress

    young girl readingThe dramatic rise in childhood cancer cure rates, from virtually zero in 1950 to around 80 percent today, is one of the major success stories in cancer treatment. 

    Even if a cure has been elusive, new chemotherapy combinations, along with improved surgery and radiation, have brought better outcomes. Cancer has become much better understood – especially in the past decade, as its genetic roots have been uncovered. Advances in diagnosis, detection, population screening, and the advent of targeted treatments like the drug Gleevec in the past decade are all making a difference. In the early 1970s, half of patients with cancer lived five years or more; today it is more than two-thirds.

    "I've had patients whom I've treated for 20 years – including two women with metastatic breast cancer – and it's extremely gratifying," Mayer observes. "Many of them are not cured, but they are living their lives in a full and robust manner. We now have more effective treatments that last a longer period of time."

    "It's like saying the only way you can score a run in baseball is by hitting a home run."

    – Robert J. Mayer, MD 

    To be sure, some types of cancer can be treated today with a very high probability that the patient will be alive five years later and probably far beyond. Childhood leukemias, thanks to the pioneering work of Farber and others, have gone from being universally lethal a few decades ago to curable in 80 percent to 90 percent of cases. Testicular cancer and Hodgkin lymphoma have high cure rates, too. In fact, Mayer points out, a patient with almost any cancer that is caught and treated early, including potentially deadly types like melanoma, pancreatic, ovarian, lung, breast, and colon cancer, has very good odds of long survival. A major challenge, however, is that some of the most lethal cancers, such as ovarian and pancreatic, are extremely difficult to detect when they can be effectively treated.

    At this point in the history of cancer and its treatment, no single yardstick of success, like the term "cure," accurately reflects what medicine can do or hopes to do in the foreseeable future.

    To measure progress only in terms of eradicating cancer misses the point, adds Mayer. "It's like saying the only way you can score a run in baseball is by hitting a home run."

    The language of the cure

    Vish ViswanathHow the word "cure" is used depends on the specific audience, says Vish Viswanath, a health communication specialist. 

    Even if the word "cure" is overused, there are times and places when it serves an important purpose, says K. Vish Viswanath, PhD, a specialist in health communication at Dana-Farber and the Harvard School of Public Health.

    "My argument is that we cannot use just one message for the public as a whole," says Viswanath. He says there are a number of different "publics," each with different needs. Among them: scientists and health providers, who speak in cautious and precise terms; people who are "engaged" with cancer – current patients and families, and longer-term survivors; and the "general public," which doesn't spend a lot of time thinking about cancer.

    "And then there is the advocacy community," Viswanath adds. "We know that the way you mobilize people around a common cause is to frame it in a way that stimulates outrage." Viewed in this light, he says, calling an event a "race for the cure" is really a metaphor – a motivational strategy rather than a concrete goal.

    Similarly, says Viswanath, there is a reason for the common military metaphors such as a "war on cancer" fought with "smart bombs" and vaccines that rally "armies" of immune cells to attack tumors. "Pithy phrases like these," he admits, "are more likely to resonate than saying, 'Our goal is to understand the molecular basis of cancer and target those gene modifications to stop cell proliferation.'"

    No amount of debate or skepticism about a cure, however, will slow the pace of research aimed at blocking the fundamental processes of cancer. Equally important, cancer specialists and organizations emphasize that much more can be done with the knowledge already gained. For example, it's estimated that about half the cancer deaths in the United States are related to tobacco use, physical inactivity, obesity/being overweight, and nutrition. It is obvious that cancer prevented is even better than cancer cured.

    Five years ago, a federal study projected that 60,000 deaths and 100,000 new cases of cancer could be prevented annually by 2015, using current early detection and prevention measures.

    Looking ahead, oncologist Mayer points to inroads being made with newer targeted treatments like Gleevec®, Tarceva®, and Herceptin® that are tailored to the genetic traits of specific patients' tumors. "It's been a remarkable decade – among other things, we've learned that one size doesn't fit all in cancer treatment," he says. "We're seeing survival improvements of 5 percent here, 10 percent there … this is not a day-and-night difference, but this is progress."

    Cancer may not be totally eliminated any time soon – or ever. Advances are generally incremental, and victories will likely come one cancer type – or subtype – at a time. But there is no denying that more lives are being saved today, and the quality of those lives is better than in the past. If this is not "a cure" in the strict sense of the word, it is surely the next best thing.

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