Cost killed the trial.
On January 7th, they voted to kill the study. "They" were a group of scientists who advise the National Cancer Institute. "The study," officially known as the Women's Health Trial, was NCI's ambitious plan to determine once and for all whether a low-fat diet can reduce the risk of breast cancer in American women.
True, the trial may have needed some costly adjustments--and the price was sky-high already. But the decision not to go ahead with NCI's only major study on fat and breast cancer jeopardizes our chances of ever learning whether diet can help prevent one of the leading killers of American women.
The design was a simple one:
1) Randomly assign 45- to 69-year-old women at higher-than-average risk for breast cancer to one of two groups.
2) Instruct the intervention group to cut their fat intake to 20 percent of calories.
3) Allow the control group to follow their usual diets, expected to be about 40 percent fat.
4) Monitor both groups for 10 years to see whether the intervention group has fewer breast cancers.
Under Attack. From the beginning, the Women's Health Trial was under attack. First, some of NCI's advisors doubted that women could stick to a 20 percent fat diet. However, an on-going feasibility trial begun in 1985 put that concern to rest.
But skeptics also worried about the control group. Might their "usual" diets drop below 40 percent over the next 10 years, as experts advise the general public to eat less fat?
"If the control group dropped much below 37 percent fat, it would weaken the study's power to detect a statistically significant difference in breast cancer rates between the two groups," explains Ross Prentice, of the Fred Hutchinson Cancer Research Center in Seattle, which spearheaded the feasibility trial. But extending the trial could have made up for the lost power, says Prentice.
Penny Wise, Dollar Foolish. Instead of lengthening the trial, NCI's advisors voted to kill it. Worse yet, they concluded that existing evidence that fat promotes breast cancer is too weak to justify any large-scale randomized trial on fat and breast cancer.
But to many observers, it wasn't weak evidence that killed the trial. It was cost.
In order to see a difference in breast cancer rates between the two groups, the Women's Health Trial would have required 32,000 women. The cost of recruiting and monitoring 32,000 women over 10 years? A cool $130 million.
A trial with a $130-million price tag can quickly make enemies of researchers who want the funding to study mammography, chemotherapy, and other means of detecting or treating--not preventing--breast cancer. Indeed, Vincent DeVita, Director of NCI, was quoted in The Washington Post as saying that this trial is being held to "a much more stringent standard than other trials."
"NCI's advisors wanted us to guarantee that the horse would win before the race began," charged David Byar, chief of the Biometry Branch at NCI's Division of Cancer Prevention and Control. "If this is the way the game will be played, how will we ever be able to use a randomized trial to study diet?"
Byar and others want a randomized intervention trial, because no other type of study can definitively determine whether fat promotes breast cancer. The two ussual alternatives are:
* retrospective case-control studies, in which researchers compare the diets of individuals who already have breast cancer (cases) to those who don't (controls), or
* prospective cohort studies, in which researchers collect diet information from a large group of healthy people, wait several years, and then compare the diets of those who developed cancer in the interim to those who did not.
But the case-control and cohort studies conducted so far are not powerful enough to detect a fat-breast cancer link. That's largely because it is extremely difficult to precisely measure how much fat people eat.
"According to our calculations, Willett's cohort trial had a 24 percent power to detect the expected difference in breast cancer rates," says Prentice. "The case-control studies are even weaker." As a rule, scientists agree that studies should have an 80 to 90 percent chance of finding a difference.
Expanding case-control and cohort studies four- to ten-fold would increase their power sufficiently, says Prentice. For example, Willett's recent study on nurses would have had to survey not 89,000 but a whopping 360,000 women.
Unavoidable Biases. But that still wouldn't rule out another problem plaguing case-control and cohort studies: biases. For example, if having breast cancer biases what a woman eats or says she eats, that would distort the results of a case-control study. "Such biases can't be ruled out because we don't know what they are," explains Prentice.
In contrast, a randomized intervention trial has none of these problems. Says Byar, "it's a much sharper tool for studying the fat-breast cancer hypothesis."
The January 7th decision left many wondering where to go from here. Some have proposed a trial that would test the effect of a low-fat diet not only on breast cancer, but on colon cancer, heart disease, and other causes of death as well. If several diseases were measured, the trial could use fewer women.
"IF we looked at total mortality, and kept the trial going longer, it would allow for a surprising decrease in sample size and a noteworthy drop in cost," says Prentice.
Even a modified trial would cost tens of millions of dollars. Because of its size and length, any trial on diet and breast cancer is, by nature, expensive. But so is cancer--in lives as well as dollars.
"It has been estimated that perhaps 35 perceent of cancer in this country is due to diet. It's the biggest single target except for smoking," says Byar. "Yet without the Women's Health Trial, we have no major study on preventing breast cancer."
Trial or no trial, NCI's advisors agreed to continue urging women--and men--to eat less fat to reduce the risk of breast and colon cancer. That's good advice, and no one can complain about the cost.
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|Title Annotation:||National Cancer Institute's planned study of the high-fat diet-breast cancer link|
|Publication:||Nutrition Action Healthletter|
|Date:||Mar 1, 1988|
|Previous Article:||Breast cancer.|
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