SAN ANTONIO -- Modest weight loss through a low-fat diet might substantially improve long-term survival in hormone receptor-negative or triple-negative breast cancer, final analysis of the WINS trial showed.

About 5 years of a dietary counseling intervention for women with early-stage breast cancer cut the cumulative mortality rate over nearly 20 years to 13.6% compared with 17.0% among controls, which wasn't statistically significant in the overall cohort (HR 0.94, 95% confidence interval 0.76-1.2).

The impact was more substantial and maintained significance, though, for hormone receptor-negative groups, Rowan Chlebowski, MD, PhD, chief of medical oncology at Harbor-UCLA Medical Center, and George Blackburn, MD, PhD, of Beth Israel Deaconess Medical Center in Boston, found.

Action Points Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Note that this post-hoc analysis of a prior randomized trial demonstrated a potential benefit of a low-fat diet in reducing overall mortality in women with hormone receptor-negative early-stage breast cancer.

Be aware that systemic therapies have changed significantly in the intervening years since this trial, which may affect the reproducibility of these results.

Estrogen receptor (ER)-negative cancer patients saw a 36% relative reduction in mortality (rate 10% versus 35%, P=0.045), they reported here at the San Antonio Breast Cancer Symposium.

Those negative for both estrogen and progesterone receptors (PR) saw a whopping 54% relative reduction in overall mortality (rate 8% versus 35%, P=0.006). The median survival differed by 2.3 years.

Chlebowski projected that 73% in that group were likely negative for HER2 as well. "This is largely a triple-negative result."

The results "really are pretty remarkable in the ER-negative subset, showing results reducing risk of death that are as good or greater than what we see with our best treatments," conference co-director C. Kent Osborne, MD, of Baylor College of Medicine in Houston, commented at a press conference he chaired.

"What it tells us is we need to pay much more attention to diet than we have in the past," Osborne told MedPage Today. "We know that the appropriate diet ... to maintain normal weight is good for your heart, it's good for everything, including maybe now breast cancer.

So it just provides more and more emphasis to oncologists to pay attention to diet when we're discussing treatment with our patients."

Chlebowski suggested that despite the lack of statistical significance in the overall group, "it's premature to say that you shouldn't do it in hormone receptor-positive patients."

The Women's Intervention Nutrition Study aimed at cutting fat intake through eliminating spreads like butter and margarine, cutting oils or fats in dressings and sauces, and reducing meat and other portion sizes.

Any diet probably would have worked, Chlebowski suggested.

While weight loss was not the aim of the intervention originally, "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 outcome."

While a randomized trial would be required to scientifically prove benefit in the hormone receptor-negative groups because all those analyses were post hoc and exploratory, there's enough evidence for clinicians to go on, Chlebowski suggested.

The mechanism for a benefit in hormone receptor-negative cancers could be complex, and sorting out exactly what in the multicomponent intervention was responsible for the benefit could be difficult, he said.

But it's more likely to be linked to glucose mechanism or inflammation than from estrogen linked to fat, he proposed.

"The other way to look at that break is the ER/PR-negative group was a no-tamoxifen group; the ER/PR-positive group was a tamoxifen group," he noted, saying that the findings will be analyzed to see whether tamoxifen interfered with weight loss.

The trial included 2,437 women ages 48 to 79 at baseline who had early breast cancer for which they had gotten surgery and systemic therapy, with or without radiation.

The intervention brought dietary fat intake down from an average of about 30% of daily calories at baseline to 20%, which resulted in 4 to 6 lbs of weight loss on average compared with controls over the 5 years of active dietary counseling.

That degree of weight loss corresponds to about 5% of body weight, which is the target for many studies for diabetes prevention and other metabolic impacts, Chlebowski told MedPage Today.

Long-term follow-up consisted only of death record checks, without any data on diet or weight change over longer-term follow-up.

The hazard ratios became significant after 3 years of cumulative follow-up, peaked at around 7 to 10 years and weakened thereafter.

For the ER- and PR-negative group, the hazard ratio for mortality reached 0.31 for intervention versus none for years 1 to 10 then attenuated to a still significant 0.46 when considering all 20 years of follow-up.

Chlebowski likened it to tamoxifen where there's a lingering effect, but one that did wear off.

During the intervention there was a 24% improvement in relapse-free survival in the overall group, but that translated to only a 6% overall survival impact, Chlebowski told attendees.

"Something was lost," he said. "Perhaps we need a longer intervention."

The study was funded by the National Cancer Institute and the American Institute of Cancer Research. Chlebowski reported relationships with Pfizer, Novartis, Amgen, Genomic Health, and Novo Nordisk.