Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women's Intervention Nutrition Study.

Journal of the National Cancer Institute

Jun 2007

DOI: 10.1093/JNCI/DJJ494

Citations:756

Influential Citations:31

Interventional (Human) Studies

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Methods

Phase III multicenter randomized trial; 2,437 women with histologically confirmed, resected unilateral early-stage breast cancer; ages 48–79; conventional breast cancer management; randomized 60% to control and 40% to dietary intervention; intention-to-treat analyses; median follow-up ~60 months; primary endpoint relapse-free survival; analyses used stratified log-rank tests and Cox proportional hazards models.

Intervention

Low-fat eating plan designed to reduce percentage of calories from fat to 15% while maintaining nutritional adequacy. Individual fat-gram goals based on energy intake needed to maintain weight. Eight biweekly in-person counseling sessions (≈1 hour each) with registered dietitians trained in motivational interviewing; subsequent contacts every 3 months; optional monthly dietary group sessions. Participants kept daily fat-gram intake in a 'keeping score' booklet.

Results

Dietary fat reduction achieved in the intervention group with lower fat intake than controls; at 12 months, fat grams/day were 33.3 vs 51.3 (P<.001). After median ~60 months, relapse-free survival favored the dietary group (277 relapse-free events: 96/975 vs 181/1462); HR 0.76 (95% CI 0.60–0.98); P = .034 for the adjusted Cox model (P = .077 for stratified log-rank). This corresponds to about a 24% lower risk of relapse. Stronger effect observed in ER-negative cancers (HR 0.58) than ER-positive (HR 0.85), but the interaction was not statistically significant. No difference in overall survival. Conclusion: a weight-maintaining, low-fat dietary intervention may improve relapse-free survival for women receiving conventional breast cancer management; longer follow-up is ongoing to complete planned endpoints.

Limitations

Interim analysis; results may change with longer follow-up. Imbalance in baseline surgical treatment (5.6% more mastectomy in the intervention group). Reliance on self-reported dietary intake without a validated gold standard. Potential weight-change confounding; adherence measurement and generalizability limited to women with resected, early-stage breast cancer.

Abstract

BACKGROUND Preclinical and observational studies suggest a relationship between dietary fat intake and breast cancer, but the association remains controversial. We carried out a randomized, prospective, multicenter clinical trial to test the effect of a dietary intervention designed to reduce fat intake in women with resected, early-stage breast cancer receiving conventional cancer management. METHODS A total of 2437 women were randomly assigned between February 1994 and January 2001 in a ratio of 40:60 to dietary intervention (n = 975) or control (n = 1462) groups. An interim analysis was performed after a median follow-up of 60 months when funding for the intervention ceased. Mean differences between dietary intervention and control groups in nutrient intakes and anthropometric variables were compared with t tests. Relapse-free survival was examined using Kaplan-Meier analysis, stratified log-rank tests, and Cox proportional hazards models. Statistical tests were two-sided. RESULTS Dietary fat intake was lower in the intervention than in the control group (fat grams/day at 12 months, 33.3 [95% confidence interval {CI} = 32.2 to 34.5] versus 51.3 [95% CI = 50.0 to 52.7], respectively; P<.001), corresponding to a statistically significant (P = .005), 6-pound lower mean body weight in the intervention group. A total of 277 relapse events (local, regional, distant, or ipsilateral breast cancer recurrence or new contralateral breast cancer) have been reported in 96 of 975 (9.8%) women in the dietary group and 181 of 1462 (12.4%) women in the control group. The hazard ratio of relapse events in the intervention group compared with the control group was 0.76 (95% CI = 0.60 to 0.98, P = .077 for stratified log rank and P = .034 for adjusted Cox model analysis). Exploratory analyses suggested a differential effect of the dietary intervention based on hormonal receptor status. CONCLUSIONS A lifestyle intervention reducing dietary fat intake, with modest influence on body weight, may improve relapse-free survival of breast cancer patients receiving conventional cancer management. Longer, ongoing nonintervention follow-up will address original protocol design plans, which called for 3 years of follow-up after completion of recruitment. show less