Findings from a long-term analysis of the Women's Intervention Nutrition Study (WINS) show that the deaths of women with hormone receptorâ€“negative breast cancers were reduced by up to 54 percent when they followed a program to reduce their dietary fat intake, which could provide benefit for patients with triple-negative breast cancer.
Findings from a long-term analysis of the Women’s Intervention Nutrition Study (WINS) show that the deaths of women with hormone receptor—negative breast cancers were reduced by up to 54 percent when they followed a program to reduce their dietary fat intake, which could provide benefit for patients with triple-negative breast cancer.
Estrogen receptor (ER)-negative patients who followed the program had a reduction of death of 36 percent, while ER- and progesterone receptor (PR)-negative patients had a 54 percent reduction of death compared to the control group.
Although the patients’ HER2 status was not available at the time of the study, based on recently published SEER data, the percentage of ER/PR-negative patients in the trial estimated to be triple-negative is 73 percent.
These findings suggest that patients with triple-negative breast cancer, who have an especially poor prognosis, could “substantially increase their chances of survival,” through a lifestyle intervention targeting fat intake associated with weight loss, said Rowan Chlebowski, who announced the results at a press conference December 12 at the 2014 San Antonio Breast Cancer Symposium.
The WINS randomized phase 3 clinical trial was launched in 1994, following on comparative studies of dietary fat intake in Japan versus the United Kingdom that suggested a possible link between fat intake and breast cancer survival along with earlier randomized trials demonstrating the feasibility of achieving dietary fat reduction in patients with breast cancer.
For the study, 2437 predominantly postmenopausal women aged 48 to 79 years were recruited from 39 clinical sites across the United States. Eligibility criteria included a diagnosis of early-stage breast cancer and receipt of standard cancer treatment, such as endocrine therapy with or without chemotherapy for hormone receptor (HR)—positive tumors, or chemotherapy for HR-negative patients, as well as radiation therapy if clinically indicated. Fifty-three percent of patients received chemotherapy, and all patients with HR-positive disease took tamoxifen. It was also required that participants’ dietary fat intake exceed 20 percent. Study accrual continued from study launch until January 2001, and the intervention ended in May 2004.
Women were randomized within six months of diagnosis to either the dietary intervention arm or the control group. Women in the intervention group were given a fat gram goal by centrally trained, registered dieticians implementing a low-fat eating plan. The women had eight, biweekly individual counseling sessions with subsequent contacts from a dietitian every three months. To monitor their own fat gram intake, women used a “keeping score” book. Patients in the intervention group were supported for a median of five years.
After a median five-year follow-up, researchers saw a 9.2 percent reduction in fat calories and a six-pound reduction in weight in the dietary intervention arm. Relapse-free survival was the study’s primary endpoint, and Chlebowski noted that relapse events were 24 percent lower in the intervention group compared with controls.
Although weight loss was not a specific target of the intervention, Chlebowski noted that “when you’re adhering to a low-fat diet, it’s pretty easy to lose some weight and we saw a statistically significant, consistent five- to six-pound weight loss,” in the intervention group.
“In the intervening 20 years, it’s become clear that weight loss is probably more important than dietary fat in terms of influencing breast cancer outcomes,” added Chlebowski, a medical oncologist at the Los Angeles Biomedical Research Institute at the Harbor-UCLA Medical Center.
The study reported at SABCS provides survival information through 2013, using death registry statistics, thus following only those participants who died. There were 250 deaths in the control group compared with 133 among those who received the intervention. Chlebowski explained that although the death rate was lower in the intervention group compared with controls, the finding was not statistically significant. For HR-positive patients, there was also no statistically significant effect from the intervention.
Other subgroup analyses yielded significant findings, however, especially in women with ER-negative cancers, who lost weight through the program. Their median survival was 13.6 years versus 11.7 years in the control group, representing 36 percent fewer deaths.
For the 362 women on the study whose cancers were both ER- and PR-negative, the improved median survival was even more significant in the intervention arm versus controls. This accounted for a 54 percent reduction in deaths within this group.
Limitations of the study include the fact that it represents an ad hoc, exploratory analysis, and the subgroup analyses were not preplanned, Chlebowski said. Nevertheless, the findings suggest a favorable lifestyle influence on survival in HR-negative subgroups during active intervention.
“When I look at these results, even with the caveats that you mention, they’re really pretty remarkable in the ER/PR [negative] subset, showing results that reduce the risk of death as good or greater than what we see with our best treatment,” noted press conference moderator Kent Osborne, professor of Medicine at the Baylor College of Medicine and director of the Dan L. Duncan Cancer Center.”
Chlebowski said that from a scientific standpoint, “others will have to look at these exploratory, post hoc analyses and decide whether they warrant support in a further randomized trial to confirm some of these findings.”
From an operational standpoint, he continued, “for a woman with breast cancer, health benefits are associated with a 5 percent, 5-pound weight loss. We’ve already seen in the randomized clinical trial setting that that amount of weight loss prevents progression from pre-diabetes to diabetes. I think this is something that a woman with breast cancer should consider.”