Womens' Health Initiative-fat reductionn diet does not reduce breast cancer risk

Another interim result report shows results which go against many other studies!:

Fat-Reduced Diet May Not Reduce Risk for Cancer or Cardiovascular Disease
Feb. 7, 2006 — At 8 years of follow-up, a fat-reduced diet was not associated with reduced risk for breast or colon cancer, heart disease, stroke, or cardiovascular disease (CVD), according to the results of the randomized Women's Health Initiative (WHI) dietary modification trial reported in 3 articles published in the February 8 issue of JAMA. Two accompanying editorials note the limitations of this trial, particularly that the diet studied is not consistent with current guidelines for a heart-healthy diet.

"The hypothesis that a low-fat dietary pattern can reduce breast cancer risk has existed for decades but has never been tested in a controlled intervention trial," write Ross L. Prentice, PhD, from the Fred Hutchinson Cancer Institute in Seattle, Washington, and colleagues. "Supported by early rodent experiments, country-to-country comparisons linked higher dietary fat intake to breast cancer risk. However, case-control and cohort studies have had mixed results."

The WHI dietary modification trial took place at 40 US clinical centers from 1993 to 2005 and enrolled 48,835 postmenopausal women, aged 50 to 79 years, without previous history of breast cancer. Of these participants, 18.6% were of minority race or ethnicity. Women were randomized to the dietary modification intervention group (40%; n = 19,541) or to the comparison group (60%; n = 29,294).

The diet was designed to reduce intake of total fat to 20% of energy and to increase consumption of vegetables and fruit to at least 5 servings daily and grains to at least 6 servings daily. Women in the comparison group were not asked to make dietary changes. The primary endpoint was incidence of invasive breast cancer.

Dietary fat intake was significantly lower in the dietary intervention group than in the comparison group, with the difference between groups in change from baseline for percentage of energy from fat varying from 10.7% at year 1 to 8.1% at year 6. In the intervention group, vegetable and fruit consumption was higher by at least 1 serving per day, and there was a smaller, more transient difference for grain consumption.

During the 8.1-year average follow-up period, the annualized incidence rate of invasive breast cancer was 655 (0.42%) in the intervention group and 1,072 (0.45%) in the comparison group (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.83 - 1.01 for the comparison between both groups). Secondary analyses suggest that there was a lower HR for women adherent to the diet, risk reduction was greater in women having a high-fat diet at baseline, and dietary effect varies based on hormone-receptor characteristics of the tumor.

"Among postmenopausal women, a low-fat dietary pattern did not result in a statistically significant reduction in invasive breast cancer risk over an 8.1-year average follow-up period," the authors write. "However, the nonsignificant trends observed suggesting reduced risk associated with a low-fat dietary pattern indicate that longer, planned, nonintervention follow-up may yield a more definitive comparison."

Limitations of the WHI dietary modification trial include reliance on self-reporting of dietary consumption; limited data to distinguish the breast cancer effect resulting from dietary fat reduction from that due to increases in the consumption of vegetables and fruit and/or grains; and limited potential to separate out the influence of any lifestyle changes or other untargeted dietary changes that may result from adopting a low-fat dietary pattern. Furthermore, departures from the design assumptions likely reduced study power, and there was a significant interaction between the HR for the intervention group compared with the comparison group for baseline dietary fat consumption. The difference in the percentage of energy from fat between the women in the intervention group and women in the comparison group was only about 70% of the design goal, and relatively few women met the dietary target of 20% of energy from fat.

The National Heart, Lung, and Blood Institute of the National Institutes of Health, Department of Health and Human Services funded the WHI program. One of the authors has disclosed that he or she is an employee of Pfizer, and another author has disclosed having various relevant financial relationships with Pfizer, AstraZeneca, Novartis, Sanofi-Aventis, Bristol-Myers Squibb, Searle, Pharmacia, Boehringer, Myogen, Merck Sharp & Dohme, and Mylan-Bertek.

In an accompanying editorial, Aman U. Buzdar, MD, from the University of Texas M.D. Anderson Cancer Center in Houston, notes that the nonsignificant trends observed and the results of secondary analyses suggest that the risk of breast cancer may possibly be modified by changing the diet. However, the specific component of dietary change responsible for the trends toward reduction in the risk of breast cancer remains unknown.

"Additional research is needed to determine the specific dietary elements that may help prevent breast cancer, the optimal time to initiate dietary interventions, and the duration these diets should be followed to achieve the maximum benefit," Dr. Buzdar writes. "In the future it may also be possible to counsel women about the optimal combined dietary and pharmacological interventions for reducing or eliminating the risk of breast cancer."

Dr. Buzdar has disclosed no relevant financial relationships.

The report on colon cancer findings by Shirley A. A. Beresford, PhD, from the University of Washington in Seattle, and colleagues, notes that there were 480 incident cases of invasive colorectal cancer during a mean follow-up of 8.1 ± 1.7 years. There was no evidence that the dietary intervention reduced the risk for invasive colorectal cancer during the follow-up period (201 women with invasive colorectal cancer [0.13% per year] in the intervention group vs 279 [0.12% per year] in the comparison group; HR, 1.08; 95% CI, 0.90 - 1.29).

Results were similar in analyses adjusting for adherence to the dietary intervention. Secondary analyses suggested potential interactions with baseline aspirin use and with combined estrogen-progestin use status (P = .01 for each).

"One explanation for a lack of intervention effect on colorectal cancer could be that the intervention did not achieve a large enough difference between the intervention and comparison groups," the authors write. "Whether greater adherence, intervention of longer duration, or initiation of change at an earlier age would influence colorectal cancer risk remain unanswered questions."

Because there was no study-specified colonoscopy or systematic screening for adenomatous polyps, the authors note that the incidence of both colorectal cancer and polyps or adenomas would be underestimated.

One of the authors has disclosed that he or she is an employee of Pfizer, and 2 other authors have disclosed having various financial relationships with Pfizer, AstraZeneca, Novartis, Sanofi-Aventis, Bristol-Myers Squibb, Searle, Pharmacia, Boehringer, Myogen, Merck Sharp & Dohme, Mylan-Bertek, Schering Plough, the Egg Nutrition Council, and General Mills.

The third article, by Barbara V. Howard, PhD, from MedStar Research Institute in Hyattsville, Md, and colleagues, addresses the effects of the WHI dietary intervention on CVD prevention. The primary endpoints were fatal and nonfatal coronary heart disease (CHD), fatal and nonfatal stroke, and CVD (composite of CHD and stroke).

By year 6, low-density lipoprotein cholesterol levels, diastolic blood pressure, and factor VIIc levels were significantly reduced by 3.55 mg/dL, 0.31 mm Hg, and 4.29%, respectively, but levels of high-density lipoprotein cholesterol, triglycerides, glucose, and insulin did not significantly differ in the intervention and comparison groups.

Annualized incidence rates were 1,000 (0.63%) for CHD, 434 (0.28%) for stroke, and 1,357 (0.86%) for CVD in the intervention group, and 1,549 (0.65%), 642 (0.27%), and 2,088 (0.88%), respectively, in the comparison group. The diet did not significantly affect incidence of CHD (HR, 0.97; 95% CI, 0.90 - 1.06), stroke (HR, 1.02; 95% CI, 0.90 - 1.15), or CVD (HR, 0.98; 95% CI, 0.92 - 1.05).

Excluding participants with baseline CVD (3.4%), the HRs and 95% CIs were 0.94 (0.86 - 1.02) for CHD and 1.02 (0.90 - 1.17) for stroke. Those with lower intakes of saturated fat or trans-fat or higher intakes of vegetables/fruits had trends toward greater reductions in CHD risk.

"Over a mean of 8.1 years, a dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women and achieved only modest effects on CVD risk factors, suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVD risk," the authors write. "These results show no effect of this diet on stroke, but a possible trend toward benefit with regard to CHD was observed."

Limitations include the lack of targeting key nutrients relevant to CVD, the focus on women aged between 50 and 79 years, self-reporting and recall bias associated with measurement of food intake, and possible overestimate of baseline percentage of energy from fat (by 2% to 3.42%).

Disclosures are the same as for the previous report.

In an accompanying editorial, Cheryl A. M. Anderson, PhD, MPH, and Lawrence J. Appel, MD, MPH, from Johns Hopkins University in Baltimore, Md, note that the trial did not test current dietary guidelines for CVD prevention, none of which focus on reducing total fat intake as a means to prevent CVD. Therefore, current policies on intakes of fruits, vegetables, and whole grains should be unaffected. However, dose-response analyses could address the health effects of lowering the current saturated fat recommendation from less than 10% to less than 7% of total energy intake and also could help define an upper level for trans-fatty acid intake.

"Despite null findings from the WHI Dietary Modification Trial, dietary changes can have powerful, beneficial effects on CVD risk factors and outcomes," Drs. Anderson and Appel write. "To reduce the risk of CVD, individuals should maintain a desirable body weight, be physically active, avoid tobacco exposure, and eat a diet consistent with national guidelines. Additional results from the WHI Dietary Modification Trial, likely forthcoming, should provide valuable evidence that will refine these recommendations and further enhance CVD prevention efforts in women."

Drs. Anderson and Appel have disclosed no relevant financial relationships.

JAMA. 2006;295:629-666, 691-69