Laura Beil

Exercise can have such a profound impact on a person’s health that some doctors have started writing down instructions to get moving on a prescription pad. Physical activity may be as powerful as anything that comes from a bottle, but how much and how often is as individual as every pill in your medicine cabinet.

The American College of Sports Medicine makes a general recommendation for cancer survivors to do 150 minutes of moderate-intensity exercise each week. In issuing the guidelines in 2010, the group pointed out that while the long-term benefits are still unknown, “Exercise training is safe during and after cancer treatments and results in improvements in physical functioning, quality of life, and cancer-related fatigue in several cancer survivor groups.”

Getting started can be the hardest part. While oncologists are great at treating cancer, they may not be the best specialists to offer specific guidance on how much exercise is best for individual patients, what type, and how often they should get out and do it, says Karen Mustian, a researcher at the University of Rochester Medical Center in Rochester, N.Y. “Start with your oncologist,” she says, “but that will probably not be enough. They will often just give general statements: ‘Of course you can exercise. Go ahead. Do something you like. Go walking.’ ”

She advises seeking out a cancer exercise trainer certified by the American College of Sports Medicine. This is a person who has special training in helping cancer survivors find—and stick with&mdash;the kind of activity that is best for them. The problem is, the certified cancer trainers are not yet in every area of the country. So it may be necessary to do some asking around to find an exercise specialist familiar with cancer.

A good trainer may also be cognizant of special considerations and risks. While cancer survivors can exercise safely the vast majority of the time—everyone can probably do something, Mustian says&mdash;some people may have complications even their doctors are unaware of. Certain treatments could have cardiac complications, or affect the immune system enough to warrant caution in crowded public gyms.

“What’s most important is you find someone you can be open with,” Mustian says. “They will listen and they will work with you to tailor an exercise prescription that meets your needs.”

[Read more about how exercise can reduce the risk of cancer recurrence in "

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Physical activity may be as powerful as anything that comes from a bottle, but how much and how often is as individual as every pill in your medicine cabinet.

The Motivation to Move

At 23, Lauren Parks was a newly minted college graduate a few months into her first job as a commercial underwriter at a San Diego bank. Lounging poolside at her apartment complex one day, she felt an itch in her right breast. When she reached to scratch it, she felt an unexpected lump.

Doctors assured her the odds of a malignancy were slim. She was too young for that. Then six months passed, and the tumor swelled to the size of an apricot, leaving no doubt an aggressive breast cancer was gathering strength. After chemotherapy, radiation and a double mastectomy, she had one singular determination: “I’m going to do everything I can to prevent this from happening again.”

But how? Parks’ oncologist advised staying active and keeping her weight under control. Treatment had left plump, unwanted curves on her naturally skinny frame. So the once uncommitted exerciser skipped the treadmill and Zumba and jumped straight into CrossFit, the fitness craze best known for its popularity among law enforcement officers, former professional athletes and suspected masochists.

Lauren Parks started her exercise regimen with the goal of preventing a recurrence of breast cancer. Photo by Megan Plenge. 

“It was so out of my comfort zone. I would have created every excuse not to go if I hadn’t gone through this,” she says. Her first time out, she found herself doing squats and throwing medicine balls. “I think I literally crawled into work the next day,” she says.

From the first burpee, she hoped to build up enough muscle for one pull-up. Today, at age 29, she can do six, a number that beats most Marine recruits. She conquered her first half-marathon this summer.

	It’s hard to say for certain whether exercise helped keep Parks cancer-free for six years. But there’s little doubt that physical activity is at the forefront of cancer prevention strategies. “A lot of patients will say, ‘What can I do to lower my odds of recurrence and increase survival?’ It’s really the question on the mind of most patients, and most oncologists as well,” says Kerry Courneya, director of the Behavioural Medicine Laboratory and Fitness Center at the University of Alberta in Edmonton. “Patients are looking for things they can do themselves. Exercise is a way to take back control over their lives.”

“He said, ‘You’re never going to get your breathing back.’ I proved him wrong.” 

	Most studies of exercise and cancer have focused on primary prevention—trying to determine whether physical activity plays a role in keeping cancer from occurring in the first place. Those data have tended to be encouraging. In general, according to Courneya, the most avid exercisers appear to have a risk of breast and colon cancer that is about 20 to 30 percent lower than that of their sedentary peers. (Protection probably exists for other types of cancer, he says, but colon and breast cancer have been studied more than other types.)

	Fewer studies have specifically examined recurrence, but those, too, generally provide reason for encouragement. For example, a study published in 2005 in the 

found that breast cancer survivors who walked three to five hours per week were about 50 percent less likely to die from breast cancer over the next four to 18 years, and the benefit tended to increase the more hours they walked. More recent research, published last year in the 

, found that among more than 3,000 women studied, those who were more active before their diagnosis were less likely to see a return of breast cancer, assuming their tumor was not driven by estrogen or progestin. Another study, this one a 2006 look at survivors of stage 3 colon cancer published in the 

, found that people who engaged in more than three hours of exercise per week were about half as likely to see a return of their disease as survivors who were inactive.

	Studies have also measured survival generally—how exercise affects the odds of dying, rather than specifically looking at cancer recurrence. A review published this year in the journal

concluded that survivors of breast cancer who engaged in at least 150 minutes per week of moderately intense exercise had a 24 percent reduction in mortality compared with their sedentary peers. For survivors of colorectal cancer who exercise at that level, mortality reduction was 28 percent.

	Sounds great, but before buying a treadmill or springing for $100 running shoes, know that doctors can’t yet say with certainty that exercise will dramatically reduce the odds of cancer coming back. For one thing, studies have been observational, meaning that the health of survivors who exercise is compared with the health of those who don’t. While a scientifically valid way to answer a question, this kind of research produces only statistical correlations— as physical activity goes up, cancer goes down.

	A good sign, but as scientists often say, correlation is not causation. Those who remain cancer-free could be making other lifestyle choices that might be improving their health and affecting recurrence. For example, those who exercise may also tend to follow a healthier diet and be more compliant with their treatment. Also, the problem with looking at survival alone is that being active conveys benefits that go beyond fighting malignancy. Exercise is well known for protecting against heart disease and diabetes, so cancer survivors might live longer because they are less likely to die from other common problems that rise in likelihood with age.

	What’s lacking is a randomized trial, in which one group of cancer survivors is assigned to do regular exercise while another is simply provided standard follow-up care. Courneya is heading up one of the few such studies. For that research, 1,000 people with colon cancer are being randomly assigned to exercise for three years while doctors note which participants see a return of cancer. The research is costing more than $6.5 million, and is being paid for by the Canadian Cancer Society and the Australian government. Unlike observational studies, the Canadian trial will be able to show cause and effect and will also estimate how effective exercise is—by what degree it actually lowers recurrence and cancer death risks. But it will not provide data for perhaps a decade.

	Still, cancer survivors don’t need to wait around in the La-Z-Boy for the results to come in. Exercise as cancer prevention makes biological sense, experts say. To begin with, physical activity helps control obesity, which a long line of evidence suggests increases the risk of cancer. In prostate cancer, for example, obesity is thought to raise the risk of aggressive malignancy. The reasons aren’t known, but fat tissue might be an accomplice to tumors by producing certain hormones that stimulate cell growth. Inflammation is another prime suspect that is reduced by exercise and elevated in obesity. Adipose tissue provokes the body’s white blood cells into a low level of activation. This quiet simmering of the immune system might damage DNA, perhaps ultimately triggering the growth of tumors.

	There’s one hitch to pointing a finger at fatness, though. Exercise alone doesn’t necessarily lead to weight loss, says Jeffrey Meyerhardt, a gastrointestinal cancer specialist at the Dana- Farber Cancer Institute in Boston. “Most people who exercise will make up their calories.” To lose weight, people have to also eat less, which doesn’t always happen.

	So physical activity might bring about other changes in the body that somehow nip the earliest buds of a tumor. The leading theory concerns how exercise affects insulin. The hormone is produced after you eat to get calories out of the bloodstream and into tissues. People develop type 2 diabetes—the most common kind&mdash;when the body becomes resistant to the effects of insulin, allowing glucose to build up in the blood. Often the body keeps pumping out higher and higher amounts of insulin in a desperate attempt to lower blood sugar, which only makes things worse.

	During exercise, the body needs calories for fuel. Insulin sensitivity increases, and levels of the hormone drop. Along with insulin, exercise lowers the body’s level of a chemical called IGF (insulin-like growth factor). Exactly how insulin and IGF fuel the growth of tumors is still being worked out, but the connection is strong enough that scientists are experimenting with using diabetes medications for cancer treatment.	

		There are still other theories to explain the connection between exercise and cancer. Meyerhardt points out that vitamin D, which the body produces naturally with sunlight exposure, is thought to be a cancer suppressor. A lot of people get their exercise by running, cycling and engaging in other outdoor sports.

		And finally, exercise could reduce recurrence by enhancing the effectiveness of cancer treatment, an idea that Courneya puts in the category of speculative, but possible. People who stay active after cancer may well have been exercising before diagnosis. “Patients who exercise during their chemotherapy may complete more of their treatment,” he says. “The other thing is that there could be some sort of synergistic effect— exercise may act as a chemosensitizer.”

		Until more answers are known, experts like Karen Mustian of the University of Rochester Medical Center in Rochester, N.Y., prefer talking about the more immediate benefits that exercise can bring to cancer survivors. “When you say the word ‘survival’ or ‘recurrence,’ those are really important words,” she says. “I’m hesitant to make any strong statements.”

		Exercise can nonetheless make life better in the short term, she says, like combating fatigue and weight gain that can be side effects of treatment. In a study Mustian and her colleagues published last year in the 

, two 75-minute yoga sessions per week improved the quality of sleep in cancer survivors. In other studies, she’s found that patients who exercise during treatment experience less memory loss and fewer problems breathing. “These are things that they feel during their treatment,” Mustian says. “I really talk about something specific.”

		It was the immediate improvement—not the specter of recurrence&mdash;that inspired Ilene Barth’s dedication to exercise after her diagnosis of lung cancer at age 53. She had been a smoker, but had given up the habit a decade earlier. She chose to have a baseline imaging scan to see if her lungs had suffered any lasting damage. The results revealed a tumor the size of a nickel. As part of the treatment, doctors removed a portion of her lung, which left her straining even to blow up a balloon for her daughter’s birthday party. “I had very good lung capacity, and then suddenly I didn’t have any,” she says. “It was scary.”

Exercise helped Ilene Barth regain lost lung capacity after surgery for lung cancer. Photo by Rita Rosenblit.

		A New York book publisher who enjoys a summer home in the mountains of Telluride, Colo., she didn’t want to give up cool, peaceful summers at 10,000 feet. “If I wanted to go home, I had to be able to breathe better,” she says. Even her doctor was not optimistic. “He said, ‘You’re never going to get your breathing back.’ ” She didn’t accept his skepticism, starting with high-altitude walks to neighbors’ houses or the local farmer’s market. She now plays tennis regularly and skis every winter. Simply put, she says, “I proved him wrong.” In fact, her pulmonary capacity is higher than it was before her surgery.

		Her cancer has stayed away for 11 years. Whether physical activity has had anything to do with it, Barth’s motivation to keep moving is more immediate: Exercise is what allows her to live like she never had cancer in the first place.

		> Exercise appears to help prevent cancer and recurrence, although research to test this idea is continuing.

		> Physical activity can help alleviate symptoms including fatigue, memory loss, sleep disturbances, weight gain and breathing problems.

To reduce the risk of cancer recurring, exercise may be just what the doctor orders.

The Fitness Factor

This kind of East-meets-West approach to cancer treatment could eventually become the norm. As more research supports the use of certain complementary methods, medical centers across the country are integrating them into everyday practice in both treatment and survivorship, giving rise to one of the newest frontiers in patient care: integrative oncology.

“There’s been a sea change in the way oncology is practiced in major centers,” says Barrie Cassileth, chief of integrative medicine service at Memorial Sloan Kettering Cancer Center in New York, author of the new book 

 advisory board. “The emphasis now in oncology is not only the best possible path to cure, but how can we control the symptoms that result from cancer treatment.”

Some doctors believe that oncology has often suffered from a loss of perspective—an almost singular focus on killing the cancer, while losing sight of patients themselves. Integrative oncology is one means of restoring balance, enabling conventional treatments to remain relentless on the malignancy but as gentle as possible on the patient. Often, that involves acupuncture, massage, yoga and even some lesserknown practices, such as music therapy and the feather touch of reiki.

These practices have long been popular and patients often use them on the side without telling their doctors. Still, experts such as Cassileth say there’s been a philosophical shift: Today doctors not only give nodding acceptance to complementary care but outright encouragement.

This new approach often surprises patients. When Joan Pouch was undergoing chemotherapy at Penn Medicine’s Abramson Cancer Center in Philadelphia in mid2011, a volunteer asked if she wanted a reiki session. “I said, ‘What is it?’ ” Pouch recalls. Until then, she hadn’t known that treatment for her stage 3 breast tumor would involve anything other than the surgerychemoradiation triple play she anticipated. That day, the volunteer gently placed her hands on Pouch’s arms and head in a practice that promotes balance and stress reduction through touch. Reiki comes from Japanese terms that translate as “universal life force.” While the scientific basis for many of these practices remains unclear, the apparent benefits are starting to attract attention among conventional researchers.

When a routine mammogram revealed Marie Jackson’s breast cancer in February 2013, she set two immediate goals. First, she wanted to spend as much time as she could behind the counter at The Flaky Tart, the Parisian bakery she owns in Atlantic Highlands, N.J. Second, she wanted to use whatever medical science she could to rid herself of the grape-size, aggressive tumor. But when the side effects of treatment started affecting every aspect of her life, she realized she needed to regain control.

Felt like I had food poisoning, a really bad hangover and the flu at the same time,” she says. “I was flat on my back.” Nauseated, worn out and more bedridden than a 47-yearold should be, she was determined to do something about it.

The emphasis now in oncology is not only the best possible path to cure, but how can we control the symptoms that result from cancer treatment?

“It was amazing,” Pouch says. After 15 minutes, she felt her anxiety begin to lift. In its place, she felt an enhanced sense of balance she had not known since receiving her diagnosis.

Not that integrative medicine is always unfamiliar. One of its mainstays is an emphasis on diet and physical activity. Studies have found that patients who exercise during and after treatment and maintain a healthy body weight tend to recover faster, feel stronger and even live longer than their sedentary peers.

“There’s a huge amount of research on the benefits of a healthy diet, physical activity and healthy body weight,” says Heather Greenlee of Columbia University in New York, president of the Society for Integrative Oncology. “Those are some of the best things patients can do to take care of themselves. But a lot of people want quick fixes. Dietary and behavioral change takes time.”

The emphasis on diet and physical activity underscores an important distinction between integrative oncology and alternative medicine. Alternative medicine choices lack scientific validity and are used in place of conventional treatment, says Lorenzo Cohen, director of the integrative medicine program at MD Anderson Cancer Center in Houston and a member of 

 advisory board. “Integrative medicine is more of a philosophy of how we treat patients,” he says. It incorporates treatments that have held up under scientific challenges, with a focus largely on improving quality of life.

Why has integrative oncology finally taken hold? Partly because of demand. The rise of integrative medicine mirrors a trend in the general population, where complementary therapies have become part of the social fabric. Data show that about four in 10 adults in the U.S. use some kind of complementary or alternative medicine—but the figure is higher among people with cancer&mdash;a huge jump from just a few decades ago. For example, one 1992 study estimated that only about 9 percent of people with cancer used complementary or alternative medicine. More recent studies put the prevalence among them in a range of 40 to almost 90 percent, particularly when prayer is included.

A study of data from more than 31,000 adults, published in 2007 in the journal 

, found that even after the cancer is behind them, survivors were still more likely than people without a chronic illness to seek complementary medicine and prayer.

Integrative medicine is more of a philosophy of how we treat patients.

The trend toward integrative therapies is also due to an unmet need in conventional medicine for more comprehensive management of symptoms and side effects, says Jeffrey White, director of the Office of Cancer Complementary and Alternative Medicine, which is part of the National Cancer Institute. Not only are people with cancer beset with immediate side effects of their treatment, but also the fierceness of the symptoms can make them feel helpless in the face of disease.

“I’ve always been very healthy,” Jackson says, so her cancer diagnosis presented not only a physical challenge but a psychological one, as well. By giving people more choices and strategies for action, integrative oncology can help restore a feeling of control.

The field also tries to steer patients to methods that are most likely to bring results. Left on their own, patients might rely on advice that isn’t always correct. (In fact, experts often lament Internet sites that make either exaggerated or wholly unproven claims.) One study of patients entering clinical trials at MD Anderson found that the most common choices for complementary therapy were vitamins, herbs and prayer. Yet, in practice, acupuncture is one of the most beneficial treatments in integrative oncology for nausea and other complaints.

“Acupuncture stands out on its own to help control symptoms,” Cohen says. “There’s good evidence in the area of controlling nausea.” This past year, in the

, Cohen and his colleagues reviewed all the studies published so far on the effectiveness of acupuncture for symptom management in cancer care, finding support for nausea relief and possibly pain. However, the jury is still out on its effectiveness for a host of other symptoms, such as fatigue and sleep disturbances. Nonetheless, he says, acupuncture’s moderate cost and few side effects make it an attractive option.

The same can be said for yoga: it’s cheap and has little chance of side effects. Yoga has also fared well in scientific studies of its value, at least during active treatment. A 2012 review published in the journal 

 of twelve randomized trials concluded that breast cancer patients who practiced yoga reported better short-term quality of life and improvement in other measures, such as anxiety, depression and stress.

Vitamin and herbal supplements, among the most common choices for people with cancer, are more difficult options for doctors to endorse beyond the level of a plain multivitamin. And unlike many of the mind-body approaches, supplements carry a more tangible risk of side effects due to their numerous biologic effects. “The most concerning area is that those particular agents may have a negative effect on conventional treatments,” Cohen says. “An example of this that is often used, but salient, is Saint John’s-wort.” Taking the herb, which might relieve mild or moderate depression, can reduce the effectiveness of some anti-cancer drugs. Studies of individual vitamins and herbs are inconsistent, Cohen says, and there are safety concerns about contamination and doses listed on the labels that do not reflect what is actually in the bottle.

Conventional medicine and complementary therapies are two worlds that still don't really intersect very well.

If there is one common wish among integrative oncology specialists, it is for more data on just about all the methods in their toolbox. “We don’t understand enough about the mechanism of action of these approaches,” White says. They can be difficult to study because of the complexity that has evolved over generations of use.

“Many of these interventions sound simple and can be described in a few words, like acupuncture,” he says. “There are more than 300 anatomical points that are used by acupuncturists in different combinations with different stimulation techniques. The effectiveness of an acupuncture treatment may depend on the choice of the points, the type of stimulation used, the skill of the acupuncturist and the frequency with which it’s done.”

Still, effectiveness data is needed to help achieve insurance coverage and relieve the financial barriers that could prevent patients from access. Some methods are provided as a part of cancer care, but many patients still pay for them out of their own pockets. And unless it’s covered by insurance, integrative oncology could remain confined to major cancer centers and not reach into communities. White still reserves one day each week for practice in a small hospital in suburban Washington, D.C., where, he says, a position such as a staff acupuncturist is unthinkable. Doctors in smaller hospitals must have some education, awareness and an interest in integrative medicine to pursue it; otherwise their patients remain mostly unaware. “Conventional medicine and complementary therapies are two worlds that still don’t really intersect very well,” he says.

[CURE-recommended integrative oncology resources]

Luckily for many patients, sometimes care is provided by volunteers, like the one who brought reiki to the bedside of Joan Pouch. Once her cancer treatments ended, she had trouble locating a practitioner near her suburban Philadelphia home. So, at age 61, she decided to learn the skill herself. Today, she volunteers at the Abramson Cancer Center every Tuesday, offering reiki to those who occupy the floors she once knew as a patient. She is not surprised to find herself delivering the care that was foreign to her just a few years ago. From the time she received her diagnosis, she looked at cancer as a journey. “I think your life is taken to the areas where you are needed.”

Patients, physicians and researchers are learning that integrative therapies have a place in cancer care.

Integrative Therapies Can Complement Conventional Cancer Treatments

Although integrative medicine includes many approaches to complement conventional therapies, according to the Society for Integrative Oncology they can be described by five categories:

3. MANIPULATIVE AND BODY-BASED PRACTICES 

Integrative medicine can be described by five categories, including mind/body, energy and ancient medical systems.

Integrative Modalities

Joan Pouch of suburban Philadelphia recalls that during her radiation treatments for breast cancer at Penn Medicine’s Abramson Cancer Center two years ago, “I sat in the waiting room with patients who said, ‘I am doing something on the side, and I’m not telling them.’”

Those patients might be more the norm than the exception. One review of studies published in 2012 in The Oncologist found wide variation in the percentage of patients who told their doctors about complementary care they were using, with some as low as 20 percent, but others as high as 77 percent. Lorenzo Cohen, of MD Anderson Cancer Center in Houston, says one study of breast and ovarian cancer patients at his center found that about half of those who were taking some kind of herb, vitamin or other product on the side had not told their physicians.

Why? “Nobody had asked them,” he says. “Another thing was they didn’t think it was important to tell anyone.” And some, he says, are reluctant to speak up because they are afraid their doctors will tell them to stop.

Doctors stress that they should be informed of anything patients are trying. Many methods, such as acupuncture or meditation, are generally considered safe, but some dietary supplements can interact with cancer treatments or exacerbate side effects like blood thinning. A review in 2008 in the 

 concluded that high doses of antioxidants during chemotherapy and radiation “should be discouraged because of the possibility of tumor protection and reduced survival.”

There is also a more basic reason for patients to talk to doctors and caregivers: They are there to help, says Heather Greenlee, president of the Society of Integrative Oncology. “Sometimes patients are trying to selfmedicate,” she says, “and there could be a therapy that is effective that they don’t know about.”

Complementary medicine was once a secret sideline for many patients. While that’s changing, communication barriers still remain.

Communication Breakdown

Biomarkers are increasingly used by patients to make decisions about cancer treatment, but they are one piece of a large, complex puzzle.

No decision is entirely right or wrong and sometimes the impact of biomarkers is subtle. The decision about which treatment to use—and when&mdash;has to take into account the entire context of the cancer’s biology and the patient’s values, goals and lifestyle. Here are factors to consider:

 The stage is the extent of disease. Generally speaking, the earlier the stage, the more treatable and curable the cancer tends to be.

How much life still lies ahead? A young father who has not yet seen his children’s milestones, graduations and weddings might want to risk aggressive treatment more than an older man who has already seen those chapters unfold. But a longer life ahead also means the greater possibility of late side effects from treatment.

 Cancer is not an exclusive disease. It can develop at the same time as other medical problems. These comorbidities must be factored into a treatment decision. For example, some cancer treatments put a strain on the heart or damage peripheral nerves, so patients with a history of heart disease or those with pre-existing nerve damage from diabetes will want to add those drugs cautiously. Cancer treatment often involves corticosteroids, which can complicate common conditions, such as diabetes.

 Now is the time for patients to think about the things they value and their life experiences. For example, a patient whose job depends on an intricate use of the hands, such as a musician or a mechanic, might be less likely to choose a treatment, such as a taxane, that carries a greater risk of causing neuropathy (nerve damage).

Patients must ask themselves and their loved ones if they want to take all necessary steps to cure the cancer. Or is there a greater desire to maintain control, even if it means the cancer won’t be cured? Or, if the cancer is advanced, is it best to opt for the greatest level of comfort instead of prolonging life? If all three considerations cannot be met, which is most important?

 Depending on the type of cancer and how advanced it is, some patients might be candidates for newer therapies that are very expensive, and insurance might not fully cover the bill. They could be forced to weigh the risk of financial distress against the odds that treatment will be successful.

Taking It Personally

"How is this even possible?” she recalls asking. As a project coordinator at the American Cancer Society’s headquarters in Atlanta, she quickly devoured every bit of information at her fingertips. “When your doctor says, ‘You have breast cancer,’ your world stops,” she says. She was relieved to know that her cancer was highly treatable. But the presence of the BRCA mutation meant that her cancer was not an unlucky fluke, but a threat programmed into her cells.

Tricia Jeffers wasn't as worried about the cancer she had as she was about the one she didn't have. During her annual checkup last year, her doctor found two lumps in her right breast. He was confident that one was a cyst. The other gave him pause, however, and a biopsy soon confirmed his suspicions. Jeffers, 41, and the mother of an 11-year-old son, had an early-stage malignancy. As part of the diagnosis and because of her young age, her doctor ordered a laundry list of genetic tests on her tumor and blood. None of her relatives had ever had breast cancer, so Jeffers was shocked when results confirmed she had inherited a genetic mutation of the BRCA2 gene that increased her risk of developing breast, ovarian and other types of cancer.

This kind of harbinger was unknown a generation ago. Yet, cancer care is heading in a new direction, as patients and their doctors are increasingly able to make treatment decisions based in large part on a cancer’s invisible biochemical clues. These bits of information, called biomarkers, only a few of which are inherited, are helping patients better understand the highly individualized risks and benefits of certain treatments.

For Jeffers, harboring an inherited BRCA2 mutation led her to decide to undergo a double mastectomy. “I didn’t want to have to go through cancer twice,” she says. “I wanted it over and done with.” Other difficult choices await: She knows she has a high risk of developing ovarian cancer, too, but is not yet ready to part with her ovaries.

This complexity is one reason the discovery of cancer biomarkers can be both a treasure chest and a Pandora’s box. There was a time when a cancer’s molecular secrets were largely a mystery, so doctors relied on the information they had in front of them to recommend treatment: How advanced was the cancer? What did it look like under a microscope? What type of tissue did it come from? But with the revolution in gene-hunting technology—enabling doctors to find genetic changes at astonishing speed&mdash;patients can make medical decisions based on the biochemical changes no one can see.

A cell’s genes contain the instructions for making all the molecules that keep life going. Cancer occurs when these instructions go haywire, allowing cells to grow with abandon. It is as if a car’s brakes fail (loss of tumor suppressor genes), or the accelerator pedal is stuck (expression of oncogenes). Some genetic flaws are inherited, others develop only in the tumor, and sometimes the genetic instructions themselves work fine, but other molecular changes keep them from turning off or on. Taken as a whole, the genetics of a cell largely control when it becomes cancerous, how fast it will grow, how hard it will be to treat, and how likely it might be to return after treatment.

The goal of testing for biomarkers is to use information about a tumor’s surface markers or genetic makeup to tailor treatment to a patient’s cancer, because one person’s breast cancer or colon cancer is probably not the same as another’s. Some doctors believe the day is coming when even the lexicon of cancer could change—instead of talking about cancer in terms of the organ or tissue from which it originates, doctors will classify cancers based on the biochemical changes hiding within.

Still, biomarker research has a long way to go. Moreover, knowing about a biomarker is only part of the decision-making equation. Doctors are keenly aware that they don’t treat just the cancer, they treat individual patients—each with different values, different hopes and different desires for the future.

In an ideal world, each person’s treatment would be exquisitely aligned with the genetic alterations that gave rise to the cancer. This isn’t yet possible, sometimes because the flaws aren’t known and sometimes because medical science doesn’t yet have drugs to address them. This means that doctors sometimes have to recommend treatments without the guidance they would like. “We still treat a lot of people who don’t need chemotherapy,” says John Marshall, chief of the division of hematology and oncology at Georgetown Lombardi Comprehensive Cancer Center in Washington, D.C.

The idea of treating cancer according to its biologic behavior is not new. The drug tamoxifen, used to treat cancers driven by estrogen, has been around for decades. But now doctors have even more insight, especially for certain cancers. “Breast cancer has led the field,” says Don S. Dizon, who specializes in treating women’s cancers at the Massachusetts General Hospital Cancer Center in Boston.

People who have an inherited BRCA mutation carry that defect in every cell of the body. Other genetic drivers of cancer arise only in the tumor cells. One of the earliest of those discovered, HER2, plays a role in about one in five patients with breast cancers and in a subset of patients with gastric cancers. Targeted drugs, such as Herceptin (trastuzumab), are designed to counteract the excess HER2 surface receptors produced by the problem gene. Today, breast cancers are routinely screened to determine whether they are overproducing the HER2 protein or if there are too many copies of the HER2 gene. Drugs that counteract the abundance of HER2 have greatly improved the outcomes of patients with this type of breast cancer.

A prognostic marker can help gauge the aggressiveness of a cancer, while a predictive marker can indicate which therapy is likely to work against a tumor. Some biomarkers, such as HER2, are both prognostic and predictive.

HER2 can accelerate certain tumors, but it can also predict the response to HER2-targeted therapies. While knowing a tumor’s HER2 status can help doctors determine which drug will be most effective, some markers can work the opposite way, indicating that certain drugs won’t work. For example, some types of KRAS mutations in those with colon cancer will not respond to EGFR (epidermal growth factor receptor) antibodies. KRAS mutations are being increasingly tested for in other cancers, including lung, but no drug has yet been developed to target the mutant protein.

One prognostic biomarker test, Oncotype DX, is used in breast, colon and prostate cancers to quantify the risk of cancer recurrence after treatment. It looks at a constellation of genes and provides a “recurrence score” that estimates the odds that cancer will return after treatment. In the case of breast cancer, it also predicts who might benefit from chemotherapy.

Another test, MammaPrint, analyzes the state of 70 genes in early-stage breast cancer to provide insight into risk of recurrence and stratify patients into lowor high-risk categories. A third, Mammostrat, also gives a recurrence score, based on the condition of five key genes, but only for hormonepositive, early-stage breast cancer.

Patients should ask their doctors if there are biomarker tests for their cancer that would help determine treatment.

Why are tests for biomarkers important? Because cancer treatments are expensive and often have serious side effects, doctors do not want to recommend drugs that won’t be helpful. As patients weigh the risks and benefits of treatments, they want to choose therapies most likely to be effective against their cancer, but least likely to cause side effects. When the drugs are specific enough, treatment can be remarkably effective.

Chronic myeloid leukemia, for example, is almost always caused by production of an abnormal protein that results from a genetic mutation called BCR-ABL. In 2001, the Food and Drug Administration approved the drug Gleevec (imatinib), which targets this protein. In one of the first clinical trials of the drug, 53 of 54 patients had normalized blood counts, usually within the first four weeks of treatment.

This kind of precision is, unfortunately, more the exception than the rule. Many kinds of cancer do not yet have enough actionable biomarkers. Marshall talks about stage 2 colorectal cancer, which he says is most likely curable with surgery up to 75 percent of the time. The problem is, medical science still can’t distinguish the 75 percent and the remainder of patients who do need adjuvant chemotherapy. “If we had a biomarker that said you were in the 75 percent, I’d pat you on the back and say exercise and eat right,” Marshall says.

During the course of treatment, checking biomarkers is not necessarily done only once. The biology of a tumor is constantly evolving as the cancer adapts to treatment and finds detours around the blockades erected by therapy. A relapsed cancer might not look like the original. “When the cancer comes back, it comes back with a different mutation profile than it had,” says Debra Leonard, chairwoman of pathology at the University of Vermont College of Medicine in Burlington, Vt.

Even though a wealth of information is now available—and more will come as technology continues to advance&mdash;patients likely won’t be able to make treatment decisions based solely on biomarkers. In some cases, biomarkers might provide knowledge about the cancer that outpaces our understanding or how to apply it, says Richard L. Schilsky, chief medical officer of the American Society of Clinical Oncology. “One of the challenges that oncologists have now is that there is a huge amount of information that comes our way,” he says. And the information from imaging scans, blood work and biomarker tests is not “completely concordant,” he adds.

One of the challenges that oncologists have now is that there is a huge amount of information that comes our way.

Neither do biomarkers provide easy answers or clear guidance. Consider the case of cancer antigen 125 (CA- 125), a protein measurable in blood that, when elevated, can be associated with ovarian cancer. The problem is, ovarian cancer is not the only factor that raises CA-125, so the number can be difficult to interpret.

Janice Sullivan of Coventry, R.I., had never heard of CA-125, and yet today the thought of it seldom leaves her mind. Now 60, she was exercising one morning in 2007 when she felt a sudden, sharp pain in her abdomen. It turned out the pain was caused by the rupture of an ovarian tumor. She received a diagnosis of stage 3 cancer and, within a week, was wheeled into an operating room.

A normal CA-125 level hovers under 35 units per milliliter. Some studies have indicated it should be as low at 20. Sullivan’s was 549 just after her surgery. Her doctors told her that quickly falling CA-125 levels indicate that a treatment is going well. When her number plummeted to 37 after one round of chemotherapy, and then into single digits shortly thereafter, Sullivan was ecstatic.

Biomarker information can help patients make medical decisions, but might not provide the clarity many patients want.

“I got very anxious,” says Sullivan, who recently retired as an elementary school principal. Her anxiety was not unfounded. A wisp of her tumor reappeared on one of her lymph nodes. Although CA-125 has been used for years to monitor for recurrence, its use after post-treatment came into question after a randomized trial showed that giving chemotherapy early after a rise in CA-125 levels rather than waiting for symptoms of recurrence failed to improve patient outcomes.

When her CA-125 number drops, “it’s wonderful,” she says. “Then it’s not wonderful. You’re living with a number.”

Through monitoring her CA-125 level, Sullivan decided to pursue experimental treatment in clinical trials, which caused more fluctuations. But, like many patients, she feels fortunate to be living during a time when more is known about her cancer. Still, there are days when she wishes she knew a little less.

The information gleaned from cancer biomarkers can be both a treasure chest and a Pandora’s box.

Biomarkers Help Patients Make Better Medical Decisions

Rita Doerner was stunned earlier this year when doctors told her she had stage 2 breast cancer. The 77-year-old from St. Louis did not have any symptoms. Although her sister died from ovarian cancer, Doerner did not think she had any particular risk. She figured genetics were on her side. “When they told me I had cancer, I didn’t believe it,” she says. In addition to standard hormone therapy, Doerner has tried a new investigational drug—one that is not specifically geared to treat breast cancer. Rather, it targets cancers with a mutation in a gene called PIK3CA&mdash;which Doerner has. Because the mutation developed in her tumor and was not inherited or present in her normal cells, it created an opportunity to intervene with a treatment that is quite specific.

The human genome is the instruction manual for assembling all the molecules that keep cells alive. It’s a biochemical code, and sometimes the coding ends up with its own bad autocorrect. Often these glitches don’t matter, but sometimes, like writing “one” when you mean “none,” a slight change makes a big difference.

A malformed molecule comes off the factory line, and like paper airplanes, the proteins of life won’t work if they’re not folded just right. When a cell collects too many misshapen molecules from bad instructions, the normal checks and balances on growth can go offline. These errors manifest in two main ways. In one instance, certain genes, called oncogenes, get switched on and can lead to cancer growth. In another situation, genes, called tumor suppressor genes, are switched off. Either way, these errors can be inherited or develop in the body over time. This is why cancer is ultimately a genetic disease, and why, in Doerner’s case, genetics were not on her side.

Researchers have long searched for genetic errors responsible for corrupting a normal cell and sending it down the path to a runaway tumor. But until recently, the hunt for cancer-causing genes was a slow, tedious and expensive process. Obtaining the sequence of a gene (reading its code) had to be done by hand, sifting through DNA bit by bit. When researchers embarked on the U.S. Human Genome Project in 1990, the job of sequencing all human genes took more than a decade to complete and cost almost $3 billion. Some of the first cancer sequencing efforts cost more than $100,000 per tumor.

But just as your car now has more computing power than an Apollo spaceship, so has genetic sequencing become more compact, affordable and nimble than scientists once thought possible. The most modern method of gene sequencing—called next-generation sequencing&mdash;analyzes genes so rapidly that scientists almost have the love-struck awe of a person who’s gone from an old-style, dial-up modem to high-speed Internet overnight.

“Before, we had to search one gene at a time, going through 20,000 genes,” says Kenneth W. Kinzler about the hunt for cancer genes. “More than two decades of research can now be repeated in a week,” adds Kinzler, an oncologist who runs a lab focused on the genetics of cancer at The Johns Hopkins University School of Medicine in Baltimore. It is now possible to quickly reveal the code for every gene inside a tumor in a couple of weeks and compare that tumor’s genes to the genetic instructions of normal tissue. All for just a few thousand dollars—bargain prices, as genomes go.

Next-generation sequencing has not only transformed cancer genetics in the laboratory; it may one day directly guide the practice of oncology. The idea is that by taking a sample of a tumor and rapidly figuring out which instructions are wrong, doctors will know where the cancer drug needs to work. (If the cancer is occurring because certain genetic mutations are allowing specific proteins to take over a cell, you know specifically what task a drug needs to accomplish.) A version of this kind of tailored care is available now only for a handful of well-studied mutations, such as HER2 in breast cancer or EGFR in colon and lung cancers. Doctors envision a day when they can expose all a tumor’s genetic tricks. “I think this is going to be standard of care, and not in 10 years, but a few years,” says Michael Snyder, director of the Stanford Center for Genomics and Personalized Medicine in Stanford, Calif. In the not too distant future, he continues, “I can’t imagine getting cancer and not getting your genome sequenced.”

That said, many hurdles—some scientific, some economic&mdash;are keeping next-generation sequencing in the laboratory and out of doctors’ offices for the time being. The challenges are substantial enough that most researchers still hesitate to predict when or how rapid gene sequencing will bring dramatic improvements for patients. Think of it this way: Simply knowing all the suspects to the crime won’t necessarily tell you which ones are guilty or how to stop them. Many genetic mutations have no known drug that works against them.

But researchers have gotten quite good at rounding up possible perpetrators. Next-generation sequencing began to evolve around the time the Human Genome Project was wrapping up but did not become widespread until recent years. In its simplest sense, next-generation sequencing is a complex, computerized process that involves slicing up DNA into tiny bits, sending them through a device that can determine the sequence of each piece one base pair at a time in parallel with thousands of pieces simultaneously and then reassembling the pieces to reveal their order. Researchers recently called this process “arguably one of the most significant technological advances in the biological sciences of the last 30 years.”

Next generation sequencing is a complex, computerized process that involves slicing up DNA into tiny bits, sending them though a device that can determine the sequence of each piece one base pair at a time in parallel with thousands of pieces simultaneously and then reassembling the pieces to reveal their order. Researchers recently called it “arguably one of the most significant technological advances in the biological sciences of the last 30 years.”

Its invention has inspired scientists to create an compendia of cancer genomic analyses, much like the Human Genome Project catalogued the genes of normal life. One effort, called The Cancer Genome Atlas (TCGA), was launched in 2006 by the National Institutes of Health with a goal of publishing information about key genetic changes for at least 20 types of cancer. Thousands of tumor samples have been donated for analysis. An international undertaking is the Collaborative Oncological Gene-environment Study, which is focusing on inherited variations of genes that increase the odds of breast, ovarian and prostate cancers.

Taken together, discoveries made in these cancer genome studies are creating a genetic road map for future treatments and detection. So far TCGA has uncovered new genes that are important to certain kinds of brain tumors, colorectal tumors, lung cancers and others. A paper published last year in the journal 

 reported finding genetic alterations important to the second most common form of lung cancer (squamous cell carcinoma), a malignancy that up to now remained a genetic mystery. And in May, two separate teams of researchers from the TCGA Research Network, writing in 

, described genetic alterations for endometrial cancer and acute myeloid leukemia. One genetic mutation found in endometrial tumors was previously thought to be important only in colon cancer.

In March, five different reports in the journal 

 revealed new findings from the Collaborative Oncological Gene-environment Study describing about 70 different inherited genetic variations (also known as polymorphisms) that increase the risk of cancer.

In general, of the genes discovered in cancer genome projects so far, “about two-thirds had previously been implicated in cancer,” Kinzler says. “The other third we had no idea were involved.” The research is also, for the first time, giving scientists a sense of just how many genetic errors add up to cancer. Common malignancies of the breast, brain, colon and pancreas can have around 33 to 66 different mutations. But melanomas and lung cancers can have more than 200 genetic errors because carcinogens, such as certain chemicals in tobacco and ultraviolet light, damage genes. Genetic studies also reaffirm that these mutations do not pop up all at once. A precancerous colon polyp may have relatively few genetic alterations, but by the time cancer develops years later, that lump of tissue might have accumulated dozens of genetic mistakes.

But cancer is not a deadly prize that goes to the tissue with the most mutations. Some childhood tumors have fewer than 10 genetic flaws. What matters is what the misguided genes are telling a cell to do. All genetic injuries are not alike, just as a broken transmission in a car is a more serious and necessary repair than a dented bumper. In other words, next-generation sequencing has made it easier to find genes gone wrong, but no drug can target all those mutations, or even needs to. The hard part is figuring out which mutations (and the molecules they affect) need to be targets of treatment. Scientists talk about “driver” and “passenger” mutations. Next-generation sequencing locates everything on the bus.

That’s why many experts are hesitant about becoming too exuberant about sequencing, at least for now. William Foulkes, director of the Program in Cancer Genetics at McGill University in Montreal, Quebec, describes himself as “healthily skeptical” about what rapid genetic sequencing means for patient care today. 

“There is more to be discovered about the complexity of the genome,” Foulkes says. Thinking of it another way, technology can search inside tumors and find mutations that doctors never knew existed—but just like a workplace with bosses, employees and opportunists waiting for their big break, each mutation occupies a different hierarchy in the operation. The most common mutations, or even the mutations most important at the moment, may not be the ones that ultimately determine the success or failure of treatment, Foulkes says. “There will always be the possibility that the mutation lurking deep in the tumor is already resistant to the drug you haven’t yet given,” he adds. Or the drug that doesn’t yet exist.

A focus of research now is how to make use of the deluge of genetic information coming out of the lab. Studies of cancer genomics have found that different mutations can have similar effects on cell growth. And, despite intense study, it’s still unclear why some tumors have the genetic programming to spread to other parts of the body, while others smolder silently for years.

Nonetheless, some companies are starting to ease cancer genomics into clinics. Kinzler from Johns Hopkins, for instance, helped found a company called Personal Genome Diagnostics in 2010 to offer genetic analysis of tumors. But for the most part, genome testing still isn’t useful enough yet to be economically feasible for an everyday oncologist’s office. More often, cancer genome analysis can help patients in research trials. An example: Researchers from Washington University in St. Louis are starting a study of women who test negative for HER2 by the standard test, but nonetheless have an “activating” mutation in the gene. They test negative, says Matthew Ellis, director of the breast cancer program at Washington University, because the mechanism behind their cancer does not require a lot of the HER2 protein to be made, which is the basis for a positive diagnostic test. They could be helped by an experimental drug that targets the mutant HER2—but neither they nor their doctors know it. “What we are doing now is finding these patients by sequencing and treating them,” Ellis says.

For too long in clinical cancer investigation, we have taken a “drug first” approach. Instead of “drug first,” what we need is “biology first.”

And even if the technology does not soon become a part of medical care, it stands to change the language of cancer. Instead of talking about malignancies from their origin—a brain tumor or colon cancer&mdash;doctors may someday classify cancers according to the genes that give a tumor its power, like Doerner’s PIK3CA mutation. Drugs will be grouped that way, too. “For too long in clinical cancer investigation, we have taken a ‘drug first’ approach,” Ellis says. Oncologists have an array of chemotherapies on hand and prescribe each agent based on assumptions of how similar tumors have responded, rather than details about the tumor’s biology. “Instead of ‘drug first,’” Ellis says, “what we need is ‘biology first.’”

The evolution of cancer genomics and what it means to you.

Future Frontier: Fighting Cancer at the Genetic Level

As physicist Albert Einstein is thought to have said, information is not knowledge. The day is coming when patients will be able to get their genome sequenced faster than they can get their dry cleaning done. But in the ethical and legal realm, the ability to obtain genetic information is advancing faster than the ability to analyze and comprehend it.

“There’s this belief that more information is better, but that’s not always the case,” says Tim Caulfield, Canada Research Chairman in Health Law and Policy at the University of Alberta in Edmonton, Alberta. As genome sequencing becomes more common, “it’s going to produce a whole bunch of ambiguous information of unclear value.”

In cancer treatment, this means sorting out the genetics that keep a tumor alive from the genetic glitches that don’t matter. But as research reveals more genes responsible for cancer, people could start looking for cancer-causing genes before there is any cancer.

Some genes, such as the BRCA breast cancer genes, confer a high risk of disease. More often, though, the genetics of cancer are more subtle, the result of lots of errors working as a whole rather than a single gene. Knowing what to make of a 15 percent risk is more difficult than knowing what to make of an 85 percent risk.

There are people who will find out about their genome and make healthy changes, such as exercising more and staying out of the sun. (Caulfield points out, however, that even more definitive predictors of disease, such as weight and high blood pressure, commonly don’t prompt choices for the better.) More likely, it could cause people to obsess over a medical problem they don’t have—and may never get&mdash;or seek preventive treatment that might bring more harm than benefit. Or they could take a fatalistic point of view and decide if they’re going to get cancer anyway, pass the cigarettes. In these scenarios, “you’re going to get no health benefit from the information,” Caulfield says.

The legal world has yet to sort out what to do with genetic sequences or how protected the information should be. Revealing the tumor’s genetics “is producing a whole lot of information that people potentially have access to,” Caulfield says. It’s still unclear who owns the information. For example, the HeLa cell line is the oldest and most widely distributed cell line in the world, grown from a tumor sample taken from Henrietta Lacks without her consent in the 1950s. In August, the National Institutes of Health announced that it would collaborate with the Lacks family to review research proposals for access to the full genome data of the HeLa cells.

“This is exciting technology that will have real benefits,” Caulfield says, “but I don’t think it’s too late to push the pause button before we use it and say ‘What is going to be the benefit to a patient day to day?’”

More information may be better when it comes to sequencing the genome, but there are some caveats to consider. 

Pressing the Pause Button

Toddlers know they are ill, but they may not understand why they need to endure multiple needle sticks and other painful procedures. Teenagers may worry about how cancer or its treatments affect appearance and peer relationships. The variability makes treating distress in younger patients particularly complex.

Even screening can be more of a challenge. Children are not going to fill out a questionnaire, and parents may have a hard time gauging a child’s emotional state. They are not little adults.

"Normally, what parents say to us is, 'My child is becoming much too quiet,'" says James Zabora, director of the Life with Cancer education and support program based in Fairfax, Va. "Parents see a change, and they don't understand it. Those are the kinds of changes that indicate to us something could be going on."

Once distress is identified, medical professionals and parents have to find unique means of reducing and treating it, both during the child’s cancer treatment and after. One study found that children who were distracted by video games, bubbles and other methods during a painful procedure were less distressed. Studies have also suggested that animal-assisted therapy and music might be beneficial to children. "Children need unique ways to try to express themselves," Zabora says, such as playing, drawing, even acting out make-believe fantasies.

And it's important to not assume the distress goes away once cancer treatment ends. Although most children tend to adjust psychologically, some may experience distress for months or years, particularly if they have noticeable disfigurement and scarring from the treatment, according to a study published last year in the 

. Former pediatric patients who were left with scars or disfigurements on their head, neck, arms or legs—visible places on the body&mdash;had about a 20 percent higher risk of depression than siblings who were not scarred.

Some aspects of cancer care might be particularly hard on adolescents and young adults because their treatment and its aftermath can affect their relationships with friends and classmates during a time of key social development. To that end, teens with greater family and social support report feeling less distress.

Social media has come to play a distinct role in helping adolescents and young adults overcome distress. For example, Planet Cancer, an online community founded by a young adult cancer survivor, has thousands of participants (

Children also experience distress, but a child's risks and coping mechanisms depend largely on age and maturity level.