SAN ANTONIO—Reducing fat in the diet can substantially increase the chance of avoiding breast cancer recurrence—especially for women with receptor negative disease, researchers reported here at the San Antonio Breast Cancer Symposium.
“The current findings with respect to long-term influence of dietary lifestyle intervention on overall survival are mixed, but of potential importance,” said Rowan Chlebowski, MD, PhD, a medical oncologist at the Los Angeles Biomedical Research Institute at the Harbor-UCLA Medical Center.
In women with estrogen receptor-negative, progesterone receptor-negative breast cancer who were trying to reduce fat consumption as part of the Women's Intervention Nutrition Study (WINS), there was a statistically significant 36 percent reduction in deaths 15 years down the road, he said.
However, that finding was an ad hoc, unplanned analysis of the WINS trial that was not part of the original protocol, leaving Chlebowski to conclude: “A lifestyle intervention targeting fat intake reduction associated with weight loss did not significantly increase overall survival of women with resected breast cancer receiving conventional cancer management.
“Exploratory analyses suggest a favorable lifestyle influence on survival in hormone receptor negative subgroups.”
But far from looking at the glass as half empty, Amy Comander, MD, a breast cancer specialist at Massachusetts General Hospital Cancer Center and an instructor in medicine at Harvard Medical School, said that the WINS trial provides compelling data that will allow her to give her patients with receptor negative status a positive message.
“As a medical oncologist I find this study particularly exciting,” she said. “I see patients every day in clinic and our patients are always asking, ‘Doctor, what else can I do? What should I eat? What should I drink? Should I take that supplement or this supplement?’ We always want to give them recommendations based on clear data. For example, there are clear data that excessive alcohol use could potentially exacerbate risk for recurrence.
“Now I can actually say, ‘There is data now for women with estrogen receptor-negative, progesterone-receptor negative tumors that if you are able to adhere to a low-fat diet, this has been shown to lower risk of recurrence and improve overall survival.’”
In the updated results of the WINS study, which is funded by the National Cancer Institute and the American Institute of Cancer Research, Chlebowski said 250 women among the 1,462 women enrolled in the control group died, 17.6 percent, compared with 133 of the 975 women assigned to intervention, 13.6 percent—“This difference was not statistically significant. The difference translated to a six percent reduction in the risk of dying.”
In the ER-positive patients, there were virtually no differences in survival between the women on the dietary intervention and those assigned to the control group. But in the 748 ER-negative patients, those women in the dietary intervention had a 36 percent relative risk reduction in mortality. The median survival for these women was 11.7 years among the controls versus 13.6 years for women who were following the dietary intervention.
In the 362 women diagnosed with both ER-negative and PR-negative breast cancer, the relative risk reduction in mortality was 54 percent in favor of the women who were in the intervention group. The median survival of the controls was 11.7 years compared with 14 years for those women in the interventional group.
Chlebowski noted that HER2 testing was not available at the time of the study, but he estimated that 73 percent of the women who were both ER-negative and PR-negative were also probably HER2 negative. “I ask you to look at this group as a largely triple-negative population,” he said.
The dietary goal of the study was aimed at reducing 15 percent of the calories from fat, although weight loss was not a goal. In the study, fat grams were lowered by 9.2 percent.
After five years, the women in the intervention group were able to lose six pounds compared with about one pound in the control group. The women in the intervention group were provided a fat gram goal by trained dieticians and attended eight bi-weekly counseling sessions and had subsequent contacts every three months. They also attended monthly group sessions. The participants self-monitored their fat intake, and their success in doing that was monitored with unannounced telephone calls.
The control group, though, wasn't just abandoned: They had contacts with dieticians every three months during the five years of the study.
After five years of dietary intervention, the average fat intake decreased from 29.6 percent of calories to 23 percent in the intervention group. At the start of the study, both groups consumed a similar amount of calories by fat—57 grams a day, or 30 percent of caloric intake, Chlebowski said. By the end of the first year, women in the intervention group had reduced their fat intake by an average of 24 grams per day compared with five grams in the control group.
The control group actually showed an increase from 29.6 to 31.4 percent, the researchers reported. However, Chlebowski noted that perhaps a third of the patients did not change their dietary fat intake in either group.
The women were about 58 years old, and entered into the study about 226 days after their surgery to resect early breast cancer. The average tumor size was just less than two centimeters “This was really a low-risk group,” Chlebowski said. About 73 percent of both groups were lymph node negative.
About 80 percent of the women in the study were ER-positive, and about two thirds were PR-positive. About two thirds had breast-conserving surgery and the rest had undergone mastectomy.
Tamoxifen Standard in 1994-2004
In the 1994-2004 era, the standard treatment was tamoxifen—47 percent of the women in each group—or tamoxifen plus chemotherapy in 38 percent of the women. About 14 percent had only chemotherapy. “All the patients received systemic therapy,” Chlebowski said.
“The signal that perhaps a lifestyle intervention targeting dietary fat intake associated with weight loss could substantially increase the chances of survival for a woman with triple-negative breast cancer could influence this group of patients. Our findings suggest that if a lifestyle intervention is to have long-term influence on clinical outcome, it must be a lifelong change rather than be a short-term alteration.”
Comander said that the failure of the estrogen receptor-positive patients to benefit from the intervention was puzzling. In theory, since fat cells produce estrogen, and reducing fat would reduce fat in the women with ER-positive tumors, that should have translated to an advantage. And the effect on patients with ER-negative cancers should have been blunted. Instead the results were exactly the opposite.
“I think these results will make us think about what the mechanisms would be to help us explain that,” she said.
She also noted the fact that HER2 evaluation was not available when the study was conducted: “So we don't really know if the patients were truly triple negative. It is likely that a substantial number of the ER-negative, PR-negative tumors were also HER2 negative.”
“I think the result among receptor-negative patients is an exciting finding. I think our patients, as a whole, are very motivated to make lifestyle changes, and now we actually have data supporting that if they are able to adhere to a low-fat diet—in this study for five years—that shows an improvement in their overall outcome. That's a pretty exciting take-home message.”