Many Americans do not think twice about taking medicines to prevent heart disease and stroke. But cancer is different. Much of what Americans do in the name of warding off cancer has not been shown to matter, and some things are actually harmful. Yet the few medicines proved to deter cancer are widely ignored. Take prostate cancer, the second-most commonly diagnosed cancer in the United States, surpassed only by easily treated skin cancers. More than 192,000 cases of it will be diagnosed this year, and more than 27,000 men will die from it.

And, it turns out, there is a way to prevent many cases of prostate cancer. A large and rigorous study found that a generic drug, finasteride, costing about $2 a day, could prevent as many as 50,000 cases each year. Another study found that finasteride’s close cousin, dutasteride, about $3.50 a day, has the same effect.

Nevertheless, researchers say, the drugs that work are largely ignored. And supplements that have been shown to be not just ineffective but possibly harmful are taken by men hoping to protect themselves from prostate cancer.

As the nation’s war on cancer continues, with little change in the overall cancer mortality rate, many experts on cancer and public health say more attention should be paid to prevention.

But prevention has proved more difficult than many imagined. It has been devilishly difficult to show conclusively that something simple like eating more fruits and vegetables or exercising regularly helps. And, as the response to the prostate drugs shows, people are not enthusiastic about taking anticancer pills, or are worried about side effects or not really convinced the drugs work. Others are just unaware of them.

And prostate cancer is not unique. Scientists have what they consider definitive evidence that two drugs can cut the risk of breast cancer in half. Women and doctors have pretty much ignored the findings.

Companies have taken note, saying that it makes little economic sense to spend decades developing drugs to prevent cancer. The better business plan seems to be looking for drugs to treat cancer. That is a sobering lesson, said Dr. Ian M. Thompson Jr., chairman of the urology department at the University of Texas Health Science Center in San Antonio.

“A scientific discovery that is very clear cut and that is not implemented by the public is a tragedy,” he said.

Few Sure Things

A few ways are known for sure to prevent cancer; the biggest is to avoid cigarette smoking. That alone would drop the cancer death rate by a third. No other measure comes close.

Another huge success, for breast cancer, is to avoid taking estrogen and progestin at menopause. Sales of those drugs plummeted in 2002 after a federal study, the Women’s Health Initiative, concluded that they did not prevent heart disease and might increase breast cancer. The next year, the breast cancer rate dropped by 15 percent after having steadily increased since 1945.

The vaccine for human papilloma virus, protects against most strains of the virus, which causes cervical cancer.

But other measures that are often assumed — and marketed — as ways to prevent cancer may not make much difference, researchers say.

For example, public health experts for years recommended eating five servings of fruits and vegetables a day to prevent cancer, but the evidence is conflicting, at best suggestive, and far from definitive.

Low-fat diets were long thought to prevent breast cancer. But a large federal study randomizing women to a low-fat or normal diet and looking for an effect in breast cancer found nothing, said its director, Ross L. Prentice of the Fred Hutchinson Cancer Research Center in Seattle.

Fiber, found in fruits, vegetables and grains, is often thought to prevent colon cancer, even though two large studies found no effect.

“We thought we would show relationships that were strong and true,” said Dr. Tim Byers, professor of epidemiology at the Colorado School of Public Health, “particularly for dietary choices and food and vegetable intake. Now we have settled into thinking they are important but it’s not like saying you can cut your risk in half or three-quarters.” Others wonder whether even such qualified support is misplaced.

There has to be a reason the research disappointed, said Colin B. Begg, chairman of the department of epidemiology and biostatistics at Memorial Sloan-Kettering Cancer Center. Perhaps the crucial time to intervene is early in life.

“That’s one possibility,” Dr. Begg said. “The other is that it’s all sort of nonsense to begin with.”

Many hold out hope for exercise or weight loss. Studies have associated strenuous exercise with less cancer. But that is the same sort of evidence that misled scientists about aspects of diet.

“I think it’s wishful thinking,” said Dr. Susan Love, a breast surgeon and president of the Dr. Susan Love Research Foundation. “We would like things to be more in our control. I think that’s part of it. And in the absence of anything else, what do we tell women about how to prevent breast cancer? We tell them to exercise and eat a good diet.”

As for obesity, researchers differ. Studies that observed large numbers of people often found that fatter people have more cancer. But many of the correlations are weak, and different studies have pointed to different cancers, raising questions about whether some of the effects are real.

Dr. Otis W. Brawley, chief medical officer of the American Cancer Society, said he was convinced. The strongest link, he and others say, is with obesity and breast cancer. But there, Dr. Brawley says, the crucial period may occur early in life — girls who gain weight when they are young, he said, tend to start menstruating earlier, which increases their breast cancer risk because it adds years of exposure to the body’s estrogen. It may be that weight loss in adulthood does not help.

“We have very little evidence that losing weight or changing diet reduces risk of cancer,” he said. “It is likely that it takes years to effect a change in risk. We do have data that the change in diet decreases cardiovascular disease risk, so it’s easier to advocate diet change.”

Others, like Donald A. Berry, head of the division of quantitative sciences at the University of Texas M. D. Anderson Cancer Center, are dubious about blaming obesity for cancer rates. If there is a risk, Dr. Berry said, he suspects it is small. The studies are relying on correlations — they cannot assess cause and effect. And studies that come up with such associations are likely to be published, even though often the associations turn out to be spurious. That means, Dr. Berry said, that “the false-positive rate skyrockets.”

Still, Dr. Prentice said, disheartening as the findings have been, it would be a mistake to give up on lifestyle changes. Instead, he said, perhaps it is time to rethink the way studies are done.

“This should be a stimulus to our research community to say, How can we conduct observational studies in a way to reveal more reliable information?” Dr. Prentice said.

Diet and exercise, he added, “are likely quite important, but we just aren’t getting the answers.”

Great Hopes Dashed

Dr. Peter Greenwald knows the dashed hopes of cancer prevention research firsthand. As far back as 1981, when he arrived at the National Cancer Institute to direct “cancer prevention and control,” Dr. Greenwald began thinking about testing whether simple measures, like vitamin supplements, could prevent common cancers.

He focused on what looked like it could be a sure thing — beta carotene, found in orange fruits and vegetables as well as in green leafy vegetables.

The body converts beta carotene to vitamin A, which can prevent cancer in rats. People eating the most fruits and vegetables had less cancer. And the more beta carotene in a person’s blood, the lower the cancer risk. Lung cancer seemed particularly vulnerable to beta carotene’s effects, particularly in smokers and former smokers.

What was needed was cause-and-effect evidence, studies showing that if people bolstered their beta carotene and vitamin A levels, they would be protected from cancer. The cancer institute decided to take it on with two large studies.

But not only did the supplements not work, but there was evidence that beta carotene might actually increase cancer risk in smokers.

Dr. Greenwald and his colleagues still held out hope for vitamins and minerals as cancer preventatives. So his group proposed the largest cancer prevention clinical trial ever tried, involving 35,000 men 50 and older. This time, the idea was that vitamin E and selenium might prevent prostate cancer.

Once again, there was presumptive evidence. But this time it was harder to persuade scientists to go ahead. After the beta carotene and vitamin A studies, several other studies had also failed to find evidence that food components or special diets could prevent cancer.

“By this time, a lot of people were very concerned,” said Dr. Scott M. Lippman, an oncologist at M. D. Anderson. He argued that the huge study had to be done. The supplements were being promoted for “prostate health,” and the evidence that they might actually work was tantalizing.

The selenium and vitamin E study ended early. Once again, there was no protection from cancer, and there were hints the supplements might be causing cancer. Once again, the great hope turned into a stunning disappointment.

Prevention researchers say they are left sadder but wiser.

“Over the years, I’ve grown more skeptical and more cautious,” said Dr. Meir J. Stampfer, a professor of nutrition and epidemiology at the Harvard School of Public Health. “Findings get reported in the literature, and the more extreme findings tend to excite the imagination. Then, as evidence accumulates, those findings are not confirmed.”

Dr. Stampfer remains optimistic, though, pointing to the story of heart disease, where softer evidence eventually led to discoveries that measures like lowering blood pressure and cholesterol could prevent disease. An amazing decline in illness and death resulted. “Cancer is harder,” Dr. Stampfer said, but he added that it is too soon to give up. Dr. Greenwald, too, has not given up. He still hopes a diet with fruits and vegetables, along with exercise and weight control, might help prevent cancer. But he knows the evidence is not definitive and scientists have been fooled before. As for Dr. Lippman, he said the field had suffered from an excess of premature enthusiasm, especially before the beta carotene studies.

“We were pulled into this,” he said. “People said, We’ve got it! There were incredibly high expectations that were, in retrospect, unrealistic.”

Claims That Go Too Far

David G. Schardt, a senior nutritionist with the Center for Science in the Public Interest, an advocacy group, likes to relax in front of his television set at night. But what he was seeing last winter made his blood boil.

“I would sit there watching network news and the ads would come on,” Mr. Schardt said. Bayer, advertising its One A Day vitamins, was saying the selenium in the pills might improve “prostate health.” And as he drove to his office in Washington, Mr. Schardt heard Bayer advertisements on the radio that actually mentioned prostate cancer.

“I couldn’t believe it,” he said. After all, the federal study had already shown that selenium was useless and might be harmful. Finally, on Oct. 1, Mr. Schardt and the Center for Science in the Public Interest filed a lawsuit.

Tricia McKernan, a Bayer spokeswoman, says the advertisements relied on the Food and Drug Administration’s “permitted qualified health claim that ‘selenium may reduce the risk of certain cancers,’ ” especially prostate cancer. The F.D.A. no longer permits that claim, Ms. McKernan noted. She said Bayer was revising its packaging and promotional materials for its One A Day Men’s and One A Day Men’s 50+ vitamins, removing references to selenium reducing prostate cancer risk.

But a subtle promotion of selenium and vitamin E by supplement makers goes on, with claims that the pills improve “prostate health” by increasing the body’s “antioxidant defenses.”

Dr. Thompson said he sees the lure of supplements when he counsels patients. “I can’t tell you how many times I talked to somebody about prostate cancer prevention,” he said. He gives the high-risk men a prescription for one of the drugs that work. But the men do not fill it.

Instead, he said, they are taking “prostate health” vitamins.

In 1990, Dr. Victor G. Vogel was at M. D. Anderson and had high hopes of changing the world. It just may be possible, he thought, to prevent many cases of breast cancer in women at high risk, a group that includes every woman over age 60, the time when the risk takes a sharp turn upward.

Dr. Vogel was to be an investigator in a huge study of 13,000 women that seemed to have everything going for it. It would test a drug, tamoxifen, an estrogen-blocker widely used to treat women with breast cancer. The studies showing the drug’s effects in breast cancer patients, though, had an unexpected bonus. It looked as if tamoxifen was also preventing new cancers in the opposite breast.

“By the time we got to 1990, there was just a huge amount of data,” Dr. Vogel said. The drug’s risks were well established and seemed well worth taking if the benefit was cutting cancer in half among women at high risk. Most side effects, like hot flashes, were temporary. But there also was a risk of blood clots similar to that conferred by birth control pills or estrogen used to relieve symptoms of menopause. And there were about two additional cases of uterine cancer per 1,000 women per year.

By 1998, the results were in. Tamoxifen cut the breast cancer rate in half. Similar studies in Britain and Italy, also involving high-risk women who had not had breast cancer, came to similar conclusions. And women did not have to take the drug for a lifetime — they needed just five years of therapy.

Dr. Vogel was ecstatic.

“If I had told you in 1990 that in 10 years I would have a pill that would cut the risk of breast cancer in half, you wouldn’t have believed me,” he said.

But, he said, to his shock, “The world said, So what?”

“We were met with shoulder shrugs and harrumphs,” Dr. Vogel said. Sales of tamoxifen, worldwide, “didn’t budge.”

Maybe, Dr. Vogel thought, the problem was that internists and gynecologists were not comfortable prescribing a drug used to treat cancer patients. Then, in 1999, he had a chance to do another breast cancer prevention trial, this time of an osteoporosis drug, raloxifene, or Evista, which did not have the cancer drug taint. It was to be compared with tamoxifen.

The $110 million study, involving 19,000 women, ended in 2006. The two drugs were found to be equally effective in preventing breast cancer, but with raloxifene there was no excess uterine cancer and the clotting risk was 30 percent less.

“It was a spectacular clinical trial,” Dr. Vogel said. But, he added, “Once again, the world met the result with a shrug and a harrumph.”

“Those were your tax dollars and mine,” he added. “You can’t do too many $110 million studies.”

He cannot understand why no one cares, but some doctors say they see a number of problems. It is usually not the cost; tamoxifen is about 30 cents a day and raloxifene $3.30 a day. It is doctors’ practices and women’s concerns.

Most doctors, said Dr. Therese B. Bevers, medical director of the Cancer Prevention Center at M. D. Anderson, do not take the first step — calculating a woman’s lifetime risk of getting breast cancer — in part because that can lead to the next step, spending an hour or so discussing cancer risk and drug risks and benefits.

Dr. Bevers suggests the drugs for women whose lifetime odds exceeds 20 percent. That could include, for example, a 55-year-old woman who began menstruating early (increasing the risk), had her first child late (again increasing the risk), and whose mother and sister got breast cancer. About half the time, though, women with that kind of risk turn down the drugs, Dr. Bevers said. “The No. 1 reason I hear is, ‘Oh, I just don’t like to take medications,’ ” she added.

Others, like Cecilia Anderson, who is 57 and lives in Houston, worry about side effects. “I felt like my quality of life was in question,” she said. “I am busy, I am out there. I totally love my life and don’t want it to be compromised.” Her lifetime risk of breast cancer is 20.5 percent, compared with an average risk of 9.8 percent for a woman her age. Ms. Anderson declined the drugs. “I live a different lifestyle,” she said. “I eat organic foods, I exercise. Through all of that comes a spiritual element as well. Mind, body, and spirit are all connected.”

Studies’ Complications

Then came the studies of finasteride and dutasteride for prostate cancer. The drugs block the conversion of testosterone to dihydrotestosterone, a hormone that prostate cancers need to grow. They are on the market to shrink the prostate in older men, whose prostates often enlarge. (Finasteride is also sold to grow hair — but the dose is one-fifth the dose that shrinks prostates and that dose has not been tested for cancer prevention.) Doctors can prescribe the drugs for cancer prevention but, at this point, that is not on their label.

The prostate cancer studies were complicated by other another factor; at first, researchers thought, erroneously, that finasteride was actually spurring the growth of aggressive prostate cancers. The drug’s side effects can include impotence or decreased ejaculate. But the Food and Drug Administration concluded that these effects, if they occur at all, are gone after a year.

Now, even though the F.D.A. deemed the drug’s adverse reactions to be “usually mild and transient.” The American Urological Association and the American Society for Clinical Oncology recommend that men 50 and older consider taking it. But there appears to be little interest even among high-risk men.

Dr. Vogel wonders what message the indifference to the breast cancer and prostate cancer drugs is sending. Why would a company want to develop drugs for cancer prevention?

That is a lesson that hits home, said Dr. Gregory Curt, an oncologist who directs emerging products at AstraZeneca, a drug company.

He hopes companies will take more interest when researchers find biomarkers — cancer risk indicators that are the equivalent of blood pressure or cholesterol. That way people taking the drugs can see that they are reducing their risk. And studies can be smaller and quicker because companies can follow these markers rather than waiting for people to develop cancer.

But risk assessment is not easy, and biomarkers are still more of a dream than a reality. There are other problems, too. If each cancer requires a different drug for prevention, how many drugs can a person take? For now, Dr. Curt said, the very idea of cancer prevention is daunting. And since cancer can take decades to develop, by the time a study concludes, a drug’s patent life may be over.

It is not a pretty picture, Dr. Vogel said.

“You have to think that in boardrooms they are saying, Man, did we learn a lesson,” he said. “We will stay as far away as possible from cancer prevention.”

Website: www.nytimes.com/2009/11/13/health/research/13prevent.html?ref=health