It is estimated that approximately 40% of all cancer cases are due to modifiable lifestyle factors. Dietary habits are widely recognized as a modifiable factor that contributes to cancer development. The large-scale Women’s Health Initiative (WHI) trial was conducted in part to assess factors potentially associated with cancer risk. The Dietary Modification (DM) component of the trial specifically tested the effect of a low-fat dietary pattern enriched in fruits and vegetables on prevention of breast cancer. In a recently published JAMA Oncology paper, researchers from the WHI Clinical Coordination Center in the Public Health Sciences Division report the effect of the DM intervention on breast cancer overall survival.
The WHI DM trial randomized 48,835 postmenopausal women to consume either a low-fat diet or a usual diet for a median of 8.5 years. After one year of dietary intervention, fat intake was lower in the intervention group, comprising approximately 24% of total energy intake as compared to 35% of that in the usual (unmodified) diet group. During the dietary intervention, 1,764 primary breast cancer cases were diagnosed, 671 in the low-fat diet arm and 1,093 in the usual diet arm (see Figure). Initial analyses of the study found that the low-fat dietary pattern led to an 8% reduction in breast cancer incidence; however, this modest reduction was not statistically significant .
Mr. Aaron Aragaki, along with Drs. Garnet Anderson and Ross Prentice, authors of the new study, described additional analyses that eventually led to the current work, “A big breakthrough occurred in a preceding WHI report that investigated the rate of invasive breast cancer followed by death from all-causes, as a composite clinical outcome.” More specifically, in that report the authors discovered “a significantly greater 19% reduction in deaths following breast cancer ,” said Mr. Aragaki.
Mr. Aragaki noted the value of these early results, stating that the findings “highlight the importance of large clinical trials with lengthy follow-up to public health. A modest reduction in fat intake, with emphasis on vegetables, fruits, and whole grains, has a positive influence on breast cancer progression and represents an easily achievable goal by many.”
Although these findings of the low-fat dietary pattern and breast cancer survival were encouraging, the analyses were conducted from the time of participant randomization which left open the question of whether the dietary intervention in the post-diagnosis period accounted for some or all of the observed beneficial effects. Thus, in the new study, the authors examined breast cancer overall survival from the time of diagnosis. After 8.5 years of dietary intervention and a median of 11.5 years of follow-up, the authors found that overall survival was significantly greater for women on the low-fat dietary intervention (see Figure). Of the 1,764 breast cancer cases diagnosed during the intervention, there were 174 deaths in the diet intervention group and 342 deaths in the usual diet group following a 40:60 randomization ratio. “This current report elucidates the significant improvement in post-diagnosis survival that resulted in 22% fewer deaths. Of note, during the dietary intervention period, dietary benefit on breast cancer overall survival increased as time from breast cancer diagnosis increased, reflecting longer duration on the low-fat intervention,” said Mr. Aragaki.
The authors then examined the cause of death for the breast cancer cases and found that in the dietary intervention group, there were fewer deaths due to breast cancer, other cancers, cardiovascular disease, and other causes. Furthermore, the beneficial impact of the low-fat dietary pattern on overall survival did not diminish after the authors adjusted for changes in body weight. Additional subgroup analyses revealed that women who were obese at baseline tended to experience the greatest benefit of the intervention diet on survival.
To follow-up on this work, the authors plan on examining the effect of the low-fat dietary pattern intervention on other types of cancer, as there is little evidence currently available on dietary fat and cancer risk. “These favorable breast cancer findings prompted interest in examining the influence of a low-fat dietary pattern on other types of cancer. While obesity and dietary fat intake are sometimes thought to have similar influence on cancer, vast amounts of evidence support the association of obesity with several types of cancer, including breast cancer . In an upcoming report, we will investigate whether dietary fat intake may be an independent risk factor for deaths from and after other types of cancer, or whether the influence of fat intake is limited to breast cancers,” explained Mr. Aragaki.
This research was supported by the National Heart, Lung, and Blood Institute, National Institutes of Health, and Department of Health and Human Services.
Chlebowski RT, Aragaki AK, Anderson GL, Simon MS, Manson JE, Neuhouser ML, Pan K, Stefanic ML, Rohan TE, Lane D, Qi L, Snetselaar L, Prentice RL. 2018. Association of low-fat dietary pattern with breast cancer overall survival: a secondary analysis of the Women's Health Initiative randomized clinical trial. JAMA Oncology. doi: 10.1001/jamaoncol.2018.1212.
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2. Chlebowski RT, Aragaki AK, Anderson GL, Thomson CA, Manson JE, Simon MS, Howard BV, Rohan TE, Snetselar L, Lane D, Barrington W, Vitolins MZ, Womack C, Qi L, Hou L, Thomas F, Prentice RL. 2017. Low-fat dietary pattern and breast cancer mortality in the Women’s Health Initiative randomized controlled trial. J Clin Oncol. 35:2919-2926.
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Maggie Burhans, Ph.D.
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Julian Simon, Ph.D.
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