Study staff screened 7572 potential participants and randomized 3107 between March 1995 and November 30, 2000 (Figure 1). There was no difference in postrandomization exclusions by study group (9 vs 10). The final study sample included 1537 women in the dietary intervention group and 1551 in the study comparison group.
The study end date was June 1, 2006. Number and frequency of reported physician visits did not differ significantly between groups at any point during the study. We confirmed vital status on the study end date (Figure 1) for 95% of the intervention group and 96% of the comparison group. Breast cancer status was confirmed for 96% of the intervention group and 97% of the comparison group.
Randomization achieved highly comparable groups (TABLE 1) with regard to demographics (ie, age, minority status, and education), breast cancer characteristics (ie, stage, grade, nodal involvement, hormone receptor status, time from breast cancer diagnosis to randomization, and eligibility for BRCA1/2 testing), and treatment (ie, surgery and radiation). Slight imbalances were observed between groups in bilateral oophorectomy, antiestrogen use, and chemotherapy treatment, all of which favored an intervention effect; however, no between-group difference was observed in the percentage of women who received at least 1 of these therapies (intervention, 93.6%; comparison, 92.3%; P=.12). Fourteen percent of women self-identified as minority race/ethnicity, and these were fairly equally divided among African Americans, Hispanics, and Asian Americans.20
In analyses of dietary change, only participants without a study end point at the time of assessment were included. A high proportion of women completed the dietary assessments (TABLE 2). At baseline, no between-group differences were observed in in-takes of vegetables, fruit, or fiber or energy intake from fat, with both groups consuming a daily mean of more than 7 servings of vegetables and fruit. No between-group differences were observed in measured mean body weight or in energy intake.
In the comparison group, consumption of vegetables, fruit, or fiber changed only modestly over the 6 years following randomization, while relative energy intake from fat increased 13%, reflecting an identified secular trend (J.P.P., V.A.N., L.N., et al, unpublished data, May 2007). In the intervention group, the dietary pattern changed substantially and a large (P<.001) between-group difference was achieved and maintained for each dietary target across the 6 years of the intervention. From no difference at baseline, the overall adherence score was 91% higher in the intervention group at 6 months and remained 61% higher than the comparison group at 6 years. Details of changes in dietary targets are presented elsewhere (J.P.P., V.A.N., L.N., et al, unpublished data, May 2007). Using the more conservative imputed data approach,27 at 1 year, the intervention group had increased average total vegetable and fruit intake to 12 servings/d. This change in total vegetable and fruit intake reflected a major increase in vegetable intake, averaging 7.8 vegetable servings/d at 1 year and remaining relatively high at 6 servings/d at the 4-year follow-up.
At 4 years, relative differences in mean intake between study groups were +65% for vegetable servings, +25% for fruit servings, +30% for fiber, and −13% for energy intake from fat. All differences were statistically significant at P<.001. Total plasma carotenoid concentration, a biomarker of vegetable and fruit intake, was 73% higher in the intervention group than the comparison group at 1 year and 43% higher at 4 years, differences that were statistically significant (P<.001). In addition, a subsample study identified changes in plasma triacylglycerol and high-density lipoprotein cholesterol concentrations that were specific to the intervention group, supporting self-reported changes in carbohydrate and fat intakes.34 Study groups differed by less than 80 kcal/d in energy intake and by less than 1 kg in body weight at any study point.
Breast Cancer Event-Free Survival
During the study, 518 participants had a breast cancer event (TABLE 3), representing 256 participants (16.7%) in the intervention group and 262 participants (16.9%) in the comparison group. The disease-free survival curves were virtually identical across groups (FIGURE 2). The unadjusted hazard ratio is presented in Figure 2. The hazard ratio after adjustment for antiestrogen use, oophorectomy status, and stratification factors (including tumor stage, clinic site, and age) at baseline was 0.96 (95% confidence interval, 0.80–1.14; P=.63). The likelihood ratio test statistics for group interactions with age, body mass index, physical activity, energy intake, characteristics of the original tumor (including hormone receptor status), and years from diagnosis to study entry were not significant (TABLE 4). Furthermore, hazard ratios for intervention effects within covariate strata were not significant (Table 4).
Intervention Effects on Additional Breast Cancer Events by Baseline Clinical and Demographic Characteristics
There were 315 deaths reported within the study period, with 155 (10.1%) in the intervention group and 160 (10.3%) in the comparison group (Figure 2). More than 80% of all deaths were due to breast cancer (Table 3). The treatment-associated hazard ratio was 0.91 (95% confidence interval, 0.72–1.15; P=.43) after adjusting for antiestrogen use, bilateral oophorectomy, and stratification factors. The likelihood ratio test statistics for the group interactions with age, body mass index, physical activity, energy intake, characteristics of the original tumor (including hormone receptor status), and years from diagnosis to study entry were not statistically significant, nor were significant effects of the intervention on mortality observed for any subgroups of women classified by major covariates (TABLE 5).
Intervention Effects on All-Cause Mortality by Baseline Demographic and Clinical Characteristics
Within each quartile of the targeted dietary components, the intervention group achieved significant change from baseline (TABLE 6). However, there was no evidence of a consistent pattern of an intervention effect for either breast cancer events or mortality according to any baseline diet subgroup, and the findings that are statistically significant in 2 of the 40 compared strata are what one might expect due to chance.
Intervention Effects on Additional Breast Cancer Events and All-Cause Mortality by Baseline Quartiles of Dietary Intake