Extra Fruits and Vegetables Don't Cut Risk of Further Breast Cancer: Results of the WHEL Study
Breast cancer, diet, cancer prevention, WHEL. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)
In the Women’s Healthy Eating and Living (WHEL) study, a diet high in fruits, vegetables, and fiber and somewhat lower in fat did not protect early-stage breast cancer survivors from further breast cancer, nor did it help them live longer than women in a comparison group. These findings contradict at least one other large study of diet and breast cancer risk. More research is needed to clarify the issue.
Journal of the American Medical Association, July 18, 2007 (see the journal abstract)
(JAMA 2007 Jul 18;298(3):289-98)
A number of studies have attempted to clarify the role of diet in the prevention of breast cancer. Results from the Women's Intervention Nutrition Study (WINS), a large randomized clinical trial reported in 2005, suggested that a low-fat diet helps prevent breast cancer recurrence in postmenopausal women, especially those whose cancers don’t respond to estrogen (ER-negative).
However, in the Women’s Health Initiative (WHI), completed in 2006, researchers found only a slight, statistically insignificant reduction in breast cancer risk among women ages 50 to 79 who were able to lower their total fat intake.
The trial described here is called the Women’s Healthy Eating and Living (WHEL) Study.
WHEL was a large phase III clinical trial that investigated whether changes in the proportion of dietary fruits, vegetables, fiber, and fat could reduce breast cancer recurrence and new primary breast cancer, as well as death from any cause, in early-stage breast cancer survivors ages 18 to 70 (see the protocol summary).
Between 1995 and 2000, at seven U.S. sites, researchers enrolled 3,088 women (mostly white) who had been treated for early stage (I-IIIa) breast cancer within the previous four years.
The women were randomly assigned to one of two dietary groups. About half the women (1,551) were asked to follow the government-recommended daily 5-A-Day diet, consisting of five servings of fruits and/or vegetables, at least 20 grams of fiber, and less than 30 percent of daily food consumption in fat. Women in this “comparison group” received a newsletter every other month and were offered an occasional cooking class, all intended to help them stick to the 5-A-Day dietary plan.
The rest of the women on the study (1,537) were assigned to an “intensive intervention” group dedicated to a more stringent diet: three servings of fruit, five of vegetables, 16 ounces of vegetable juice, 30 grams of fiber, and only 15 to 20 percent of fat. With the stricter diet came a robust support program. Women in this group received more frequent newsletters, were offered more cooking classes, and – unlike the comparison group – received regular telephone calls from counselors offering encouragement and coaching.
At the start of the trial, all of the women reported eating about seven fruit and/or vegetable servings a day. Also, the two groups were similar in terms of average body weight and the average number of daily calories consumed.
To gather dietary data, researchers telephoned participants throughout the study, asking them to recall what they had eaten for the previous 24 hours. A follow-up assessment was completed by most women after the study ended June 1, 2006. As a way to check on the participants’ self-reports, women in both groups provided blood samples during the study that were analyzed for biomarkers measuring their fruit and vegetable intake.
The study’s lead author was John J. Pierce, Ph.D., from the University of California-San Diego. WHEL was initiated as a pilot study funded by a grant from the Walton Family Foundation, and continued with funding from the National Cancer Institute.
There were significant differences between the two groups in terms of their food intake during the course of the study. At the four-year mark, women in the intensive intervention group were eating 65 percent more vegetables, 25 percent more fruit, 30 percent more fiber, and 13 percent less fat than women in the comparison group. The biomarker indicating fruit and vegetable intake was also 43 percent higher in the intensive intervention group.
However, after a median of 7.3 years of follow-up, there were no statistically significant differences in terms of the study’s main endpoints. About 17 percent of women in each group had a breast cancer recurrence or a new primary breast cancer, and about 10 percent died in each group, more than four in five of them due to breast cancer. All of the women had received similar clinical care.
Though they ate significantly more fruit and vegetables than women in the comparison group, women in the intensive intervention group never managed to reduce their daily fat intake to between 15 and 20 percent of their diet. They never got below 21 percent and by the end of the trial were averaging more than 27 percent (as were the women in the comparison group).
Near the end of the seven-year follow-up period, women in both groups were reporting fat intake averages higher than what they’d reported at the start of the study.
Another problem (common to dietary studies) was the difficulty in validating the participants’ reports of what they ate. The periodic blood tests were able to confirm self-reports of fruits and vegetable intake, but not fat. Researchers noted that while women in both groups reported eating fewer calories per day at the end of the study compared to the beginning, all participants on average experienced slight gains in weight – a puzzling occurrence suggesting the women’s calorie reports may have been less than fully accurate.
The WHEL authors say these results fairly demonstrate that early-stage breast cancer survivors do not protect themselves against further breast cancer by adopting a diet very high in fruits, vegetables, and fiber and somewhat lower in fat. However, counters John Milner, Ph.D., chief of the Nutritional Science Research Group at the National Cancer Institute (NCI), such a conclusion should not be taken as final. Researchers are continuing to follow the participants and are also conducting subset analyses.
“I would be surprised if the ongoing analysis of genetic and other factors failed to identify one or more WHEL subgroups of women who did have a meaningful risk reduction,” says Milner.
As one example, says Sharon Ross, Ph.D., MPH, the NCI’s project director for WHEL, “we have a rich database of information on [the participants’ use of] dietary supplements, such as vitamins and minerals” that might uncover risk differences based on a more comprehensive picture of total nutrition.
In addition, notes Milner, “not all fruits and vegetables are equal” in terms of their overall effect. “Even if you had an accurate report of how much of which food was consumed, the food supply itself is subject to enormous variations in terms of the purity and strength of food components. Plus certain interactions occur when various components are blended.”
“The conflicting results from the WHEL study and WINS…require careful consideration,” write cancer specialists Susan M. Gatspur, Ph.D., and Seema Khan, M.D., of Northwestern University in Chicago, Ill. in an editorial accompanying the published results.
In the WINS study, early-stage breast cancer survivors on the low-fat diet (15 percent of total daily calories) weighed, on average, about six pounds less than a comparison group at the end of five years. In WHEL, women on the lower-fat diet lost no weight relative to the comparison group. “These data support findings from observational studies suggesting that a high level of obesity, weight gain, or both after [breast cancer] diagnosis” raises women’s risk of further disease and death, say Gatspur and Khan.
“It is unclear whether the difference in energy balance, as reflected by weight change, partly accounts” for why WINS participants on the low-fat diet lowered their risk of breast cancer recurrence and death while WHEL participants did not, they say.
Another potentially meaningful difference between the two studies is that women in WHEL were 18 to 70 years old, whereas all WINS participants were postmenopausal.
“It is becoming increasingly clear that evaluating dietary effects is complex,” write Gatspur and Khan, “and requires careful monitoring to ensure adherence to the intervention goals.”
Nonetheless, Milner emphasizes that “we have a lot of good evidence that fruits and vegetables reduce heart disease.” What’s more, says Ross, “despite complex and at times controversial data, enough evidence is available to suggest that weight management should be part of a strategy for cancer survivors to reduce their risk of recurrence.”
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