In this randomized trial of a dietary intervention to achieve a substantial change to a diet very high in vegetables, fruit, and fiber and low in fat, the risk of developing additional breast cancer events and survival were not altered in women previously treated for early stage disease. No significant benefit in recurrence was observed overall among population subgroups characterized by demographic characteristics, baseline diet, or initial tumor types. Although breast cancer mortality rates in the United States declined during the study period,35 the similarity in survival patterns between the WHEL Study groups suggests that continued follow-up would not alter the study results.
It is unlikely that our results were materially affected by bias in assessing the main study end points. Follow-up of participants was nearly complete and did not differ between study groups, and we considered only reports of recurrence and new primary tumors that were validated by medical record review. We observed large and sustained between group differences in vegetable and fruit intake, as assessed by self-report and plasma carotenoid concentrations, a biomarker of vegetable and fruit intake. We also observed significant differences in fiber and fat intake. Although weight has been associated with health outcomes, we observed less than a 1-kg difference in average weight between WHEL Study groups at any time point. While psychosocial factors have been linked with health outcomes, we found no between-group differences for depression, social support, or quality of life during year 1, when the intervention was most intense.36 Therefore, we believe that our investigation provides an adequate test of whether the study dietary pattern (very high in vegetables, fruit, and fiber and low in fat) provided an added benefit over the dietary pattern of the comparison group women.
Many WHEL Study participants had likely changed their dietary pattern since receiving a diagnosis of breast cancer37; 75% were consuming at least 5 servings of vegetables and fruit a day at randomization, an intake that is considerably higher than that observed in other populations of breast cancer survivors.38,39However, we observed little evidence of recurrence benefit in the quartile of the intervention group that was consuming less than 5 daily servings of vegetables and fruit at baseline, despite a major change in dietary pattern that was specific to the intervention group. Previously, in longitudinal analyses of the comparison group only, we observed a possible threshold effect on recurrence for low levels of baseline plasma carotenoid concentration13 and also that a baseline combination of 5 fruits and vegetables a day and physical activity equivalent to walking at a moderate pace for 30 minutes, 6 d/wk, was associated with lower mortality.14 However, in this analysis of data from the randomized trial, a major increase over the 5-a-day dietary pattern was not associated with reduced breast cancer events or mortality.
We suggest caution in applying our findings to groups of women other than those represented in our study, which was confined to women who had already completed initial therapy for breast cancer and excluded women with diagnoses after age 70 years and those with stage 1 tumors smaller than 1 cm. Also, only 14% of our study population was self-identified as from African American, Hispanic, and Asian American racial/ethnic groups.
Our finding that reducing dietary fat intake did not benefit breast cancer outcomes appears at odds with the interim analyses from the Women’s Intervention Nutrition Study (WINS), which concluded that reducing dietary fat intake was marginally associated with longer relapse-free survival of breast cancer patients, an effect most noted in the subgroup with estrogen-negative tumors. However, differential follow-up between intervention and comparison groups may have influenced the WINS finding.40 Furthermore, the reduced body weight observed only in the intervention group might partially account for the improved relapse-free survival in WINS.41In addition, although WINS reported an 8% to 9% between-group difference in energy intake from fat maintained through 5 years, they reported a higher rate of missing dietary intake data in the intervention group. At the 3-year point, data were available for 67% of the intervention group vs 74% of the comparison group. At 5 years, data were available for 39% of the intervention group and 44% of the comparison group. If even moderate proportions of nonresponders increased their fat intake, the between-group effect could well be less than the absolute 4% difference that we observed. Finally, it is important to note that the women enrolled in WINS differed from those in the WHEL trial regarding prognosis following the original diagnosis, age, and treatment regimen.
Although the WHEL Study’s intervention diet focused mainly on increasing vegetable, fruit, and fiber intake, there was a significant between-group difference in fat intake. However, this difference may not have been sufficient to test the dietary fat hypothesis adequately. Unlike the changes observed for intakes of vegetables, fruit and fiber, the smallest dietary fat change was made by participants in the quartile that was furthest from the study target at baseline. Nonetheless, our analyses did not suggest an effect across quartiles of fat intake at baseline, nor did our results indicate an intervention effect in subgroups defined by hormone receptor status, as was seen in WINS.
The absence of an observed effect on breast cancer events or all-cause mortality over a 7.3-year follow-up period in this study does not rule out the possibility of improved longer-term survivorship within this cohort. We did not explore the possibility that increased exercise and weight loss might benefit breast cancer survivors. Finally, our study did not address whether consuming the high–vegetable/fruit/fiber and low-fat diet of our study intervention early in life would alter risk of primary breast cancer.
In conclusion, during a mean 7.3-year follow-up, we found no evidence that adoption of a dietary pattern very high in vegetables, fruit, and fiber and low in fat vs a 5-a-day fruit and vegetable diet prevents breast cancer recurrence or death among women with previously treated early stage breast cancer.