Postmenopausal women eating a low-fat diet had a nonsignificant lower risk of death from breast cancer and a significantly reduced risk of death from other causes after breast cancer than did women following their usual diet, long-term follow-up data from the Women's Health Initiative Dietary Modification (WHI DM) trial confirmed.
During the 16.1-year cumulative follow-up, with 3,030 incident breast cancers, a significant reduction was seen in all-cause mortality in the dietary intervention group compared with the usual-diet group, with 234 deaths versus 443 deaths, respectively (0.085% per year versus 0.11% per year; HR 0.82; P=0.01), according to Rowan T. Chlebowski, MD, PhD, of City of Hope National Medical Center in Duarte, Calif., and colleagues.
Over the same period, there were "somewhat fewer" deaths due to breast cancer observed in the dietary group compared with the usual-diet group: 111 deaths versus 185 deaths per year, respectively (0.035% per year versus 10.039% per year; HR 0.91; P=0.01), the researchers reported online in the Journal of Clinical Oncology.
Women in the low-fat diet group also had a weight loss of 3% (2.2 kg; P< 0.001), which was maintained throughout the 8.5-year dietary intervention period.
"With long-term follow-up of the WHI DM trial, deaths after breast cancer were significantly reduced in the dietary group both during the dietary intervention period and throughout the 16.1-year cumulative follow-up period," the study authors wrote. "Overall, 9% fewer deaths occurred as a result of breast cancer (n = 296; P=0.41), and 18% fewer deaths occurred after breast cancer (n = 677; P=0.01) in the dietary group. Future studies of other lifestyle interventions on breast cancer incidence and outcome could incorporate some form of a low-fat dietary pattern as a base."
In an email to MedPage Today, Chlebowski said: "The findings are suggestive that adoption of a low-fat eating pattern associated with modest weight loss may favorably influence breast cancer outcome. I think the findings have implications for the breast cancer adjuvant setting, but that issue was not directly addressed."
He emphasized that the study's conclusions have to be qualified, since the analyses were not "protocol specified, and this was a primary prevention trial." In addition, about half of the dietary intervention was carried out prior to a diagnosis of breast cancer and the other half was after diagnosis. Moreover, he said, the effects of the low-fat eating pattern could not be definitively separated from those of weight loss on the study outcome.
In an interim report at the end of the 8.5-year dietary intervention period, Chlebowski and colleagues noted 1,764 incident breast cancers, with 27 deaths in the low-fat diet group compared with 61 deaths in the usual-diet group (0.016% per year versus 0.024% per year, respectively; hazard ratio [HR] 0.67; P= 0.08). Although this result was non-significant, deaths after breast cancer were significantly reduced by dietary intervention (40 deaths versus 94 deaths; 0.025% per year versus 0.038% per year; HR 0.65; P=0.02), the team reported.
The interim findings also suggested that a low-fat eating pattern could reduce the incidence of breast cancers associated with higher rates of mortality. And in fact, while the characteristics of participants were similar in both study groups, more women in the dietary intervention group had estrogen receptor-positive (ER+), progesterone receptor-negative (PR–) human epidermal receptor 2 ( HER2)-negative breast cancers than those in the usual-diet group did.
"The lower risk of poor prognosis contributed to the favorable dietary effect on death after breast cancer," the study authors said, adding that this explains 29% of the difference in deaths after breast cancer.
One possible explanation is that dietary intervention-reduced breast cancers are more likely to be fatal and to favorably influence other causes of death: "Because the WHI low-fat dietary intervention had at least short-term effects of lowering systolic blood pressure, reducing metabolic syndrome risk, and lowering cholesterol-targeted and hypertension medicine, it could have had an influence on other chronic diseases," the investigators suggested.
For the study, 48,835 postmenopausal women ages 50 to 79 with normal mammograms and no prior history of breast cancer were enrolled at 40 clinical centers in the United States. From 1993 to 1998, 19,541 women (40%) were randomly assigned to a dietary intervention that reduced fat intake to 20% of calories and increased intake of fruits, vegetables, and grains, while a comparison group of 29,294 women (60%) were given diet-related education materials.
Dietary group participants received nutrition counseling throughout the intervention period, while comparison group participants received written diet-related education materials.
Subgroup analyses identified postmenopausal women as being more likely to benefit from the dietary intervention if they previously had a high-fat diet with 37% or more of daily calories coming from fat, or a high BMI with a waist circumference of 88 inches or greater.
"Because subgroup analysis identified no benefit on deaths after breast cancer for dietary group participants, with <27 .9="" a="" at="" be="" calories="" effect="" entry="" fat="" for="" from="" may="" notional="" threshold="">28% calories from fat, which is not far from the current average U.S. intake of postmenopausal women of 33%," the study authors said. "A modest reduction in fat intake with minimal weight loss represents an easily achievable goal by many.27>
Chlebowski said that clinicians can decide if they want to discuss these findings with their breast cancer patients. "They could refer to a registered dietitian for implementation," he suggested, noting that this would not be reimbursed by insurance.
Three ongoing clinical trials evaluating similar lifestyle interventions could provide more evidence, he added: DIANA (Diet and Androgens)-5; SUCCESS C; and BWEL, the Breast Cancer Weight Loss Study.
The study was supported by the National Heart, Lung, and Blood Institute; the American Institute for Cancer Research; and the National Cancer Institute.
Chlebowski reported financial relationships with Novartis, Genentech, Amgen, Pfizer, and AstraZeneca. Two other coauthors also made disclosures: Garnet L. Anderson, PhD, for relationships with Pfizer, Johnson & Johnson, and Mars Symbioscience; and Thomas E. Rohan, PhD, MBBS, DHSc, reported royalties on a patent for tumor microenvironment of metastasis.