Long-awaited survival data from the Women's Intervention Nutrition Study (WINS), which began in 1994 and evaluated a low-fat diet intervention as an adjuvant breast cancer therapy, show that there was no statistically significant reduction in mortality in the overall study population.
However, there was a significant effect seen in a small subgroup of patients with hormone receptor (HR)-negative disease, where there was a 2.2-year benefit in median overall survival in the women who were in the diet intervention group, compared with control subjects.
Although this finding comes from an exploratory post hoc analysis, this is "the most intriguing part of the results," said lead researcher Rowan Chlebowski, MD, PhD, medical oncologist at the Los Angeles Biomedical Research Institute at the Harbor-UCLA Medical Center.
However, he described the results overall as being "mixed".
"I wonder if you shouldn't be stronger in your conclusions," commented Kent Osborne, MD, director of the Dan L. Duncan Cancer Center at the Baylor College of Medicine in Houston, who moderated the press briefing at which the study was highlighted here at the San Antonio Breast Cancer Symposium (SABCS) 2014.
Although taking on board the caveat that this was a result from a post hoc analysis, Dr Osborne said the result in the hormone-negative population was "pretty remarkable," and the effect is "as good as or even greater than we see with our best treatments."
"All of us, as oncologists, should take dietary intervention more seriously," Dr Osborne said. "Oncologists should have a mechanism for referring patients to a nutritionist who can counsel them about diet. I think we need to take this far more seriously that we have in the past," Dr Osborne told Medscape Medical News.
Dietary Intervention Targeted Fat Intake
The WINS trial enrolled 2437 women (48 to 79 years) with early-stage breast cancer who received standard care (surgery ± chemotherapy). In addition, tamoxifen was used in women with estrogen receptor (ER)-positive tumors, present in 1597 women (65% of the total).
The dietary intervention specifically targeted fat intake reduction through regular individual counseling sessions with dieticians. Dr Chlebowski said that this involved cutting out butter and margarine, cream and oils (e.g., from salad dressings), and avoiding fatty meat, such as sausages, etc.
Women in the intervention group were given a fat-gram goal by centrally trained, registered dieticians implementing a low-fat eating plan, explained Dr. Chlebowski. The women underwent eight biweekly individual counselling sessions with subsequent contacts every 3 months. The women self-monitored their fat/gram intake using a "keeping score" book, and fat intake was externally monitored by unannounced 24-hour telephone recalls performed annually, he said.
After a median of 5 years on this low-fat eating plan, the women in this intervention group had significantly reduced fat intake (from 29.2% to 20.3% of calories; P < .0001) and had significant weight loss of about 5 to 6 lbs (2.7 kg) (P = .005), whereas the women in the control group showed no change.
However, there was some overlap between the 2 groups, Dr Chlebowski noted, with about a third of women in the control group showing similar weight loss to those in the intervention group. If this was a drug vs placebo trial, it would be equivalent to more than 30% of the control group actually taking the active drug instead of the placebo.
Dr Chlebowski noted that that since the trial was started, it has emerged that it is weight loss rather than fat intake that is important for breast cancer risk reduction.
An earlier report from the WINS study, at 5-year follow-up, showed a significant effect on breast cancer recurrence, as reported by Medscape Medical News at the time and subsequently published (J Natl Cancer Inst. 2006;98:1767).
This 5-year follow-up showed that the breast cancer recurrence rate was 24% lower in the dietary intervention group than in the control group (hazard ratio [HR], 0.76; P = .03).
Dr Chlebowski noted that funding for the study finished in 2004, and since then there had been no contact with individuals. Further follow-up has been only through death registry data, which was continued until 2013 (with a follow-up of up to 19.4 years).
The survival data at this 19-year follow-up show that in the overall population there was no significant effect on mortality (13.6% in intervention group vs 17% in control group; HR, 0.82; P = .146).
The result was similar in the large subgroup of women with ER-positive disease, with no significant effect on mortality. Dr Chlebowski noted that these women were taking tamoxifen, and speculated that tamoxifen may have interfered with the weight loss from the dietary intervention.
However, in the small subgroup of women with ER-negative tumors (n = 478; 19.6% of total), there was a 36% reduction in deaths (all-cause mortality) in the intervention group, compared with the control group (HR, 0.64; P = .045). Median survival was 1.9 years greater for the intervention group than the control group (13.6 vs 11.7 years).
The reduction was even more significant for women with cancers that were both ER- and progesterone-receptor-negative (n = 362; 15% of total), Dr Chlebowski said, with a 56% reduction in death (P = .006). Here, median survival was 2.2 years longer in the intervention group, compared with the control group (14.0 vs 11.7 years).
Although testing for HER2 was not available at the time this trial was started, he suspects that many of these women (over 70%) would also be HER2-negative and have triple-negative breast cancer. These patients generally have a poor prognosis, so a signal here of a substantial effect on survival is of interest, he said.
This is of interest, said Beverly Moy, MD, clinical director at the Massachusetts General Hospital Cancer Clinic in Boston. "This is an important study with potentially important clinical implications," she told Medscape Medical News. "We have seen previously from this study a significant effect from the low-fat diet on disease progression, and these new data on survival, although they are not significant for the population overall, they are statistically significant in the subgroup of women with ER-negative disease."
This is important because these patients have fewer therapeutic options, and these patients tend to have more aggressive disease, she told Medscape Medical News.
Really good studies on lifestyle intervention are lacking, but this study shows clearly that a low-fat diet resulting in weight loss really can improve outcomes. This is something we can discuss with our patients, and this is something that they can do, she added.
"We hear all the time from our patients, what can I do to give myself the best chance of cure?" she commented. "Now we can say that a low-fat diet with weight loss can improve your outcome, and this is fantastic," she added. "I'm delighted that there is real evidence from a randomized trial to show that there is benefit."
Although this study didn't show a specific effect on survival in the overall population of breast cancer patients, there are other studies that have shown benefits from exercise and weight loss, and there is also evidence from subgroup analyses of large adjuvant studies that show clearly that women who have ER-positive disease who are obese have a significantly worse outcome. "So I think that you can generalize and say that it's never a bad idea to live a good lifestyle," she said, adding that it also has benefits for overall health, reducing cardiovascular, and diabetes risks.
The WNIS study was funded by the National Cancer Institute and the American Institute of Cancer Research. Dr Chlebowski reports receiving consulting support from Pfizer, Novartis, Amgen, Genomic Health, and Novo Nordisk, and honorarium from Novartis.
San Antonio Breast Cancer Symposium (SABCS) 2014: Abstract S5-08. Presented December 12, 2014.
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Cite this: Low-Fat Diet Improves Survival in Some Breast Cancer Patients - Medscape - Dec 15, 2014.
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