Association of Low-Fat Dietary Pattern With Breast Cancer Overall Survival: A Secondary Analysis of the Women's Health Initiative Randomized Clinical Trial

Abstract

Importance: In a randomized clinical trial, a low-fat eating pattern was associated with lower risk of death after breast cancer. However, the extent to which results were driven by dietary influence on survival after breast cancer diagnosis was unknown.

Objective: To determine the association of a low-fat dietary pattern with breast cancer overall survival (breast cancer followed by death from any cause measured from cancer diagnosis).

Design, setting, and participants: This is a secondary analysis of the Women's Health Initiative randomized clinical trial that was conducted at 40 US clinical centers enrolling participants from 1993 through 1998. Participants were 48 835 postmenopausal women with no previous breast cancer and dietary fat intake of greater than 32% by food frequency questionnaire.

Interventions: Participants were randomized to a dietary intervention group (40%; n = 19 541) with goals to reduce fat intake to 20% of energy and increase fruit, vegetable, and grain intake or a usual-diet comparison group (60%; n = 29 294). Dietary group participants with incident breast cancers continued to participate in subsequent dietary intervention activities.

Main outcomes and measures: Breast cancer overall survival for incident breast cancers diagnosed during the 8.5-year (median) dietary intervention, examined in post hoc analyses after 11.5 years (median) postdiagnosis follow-up.

Results: Of 1764 women diagnosed with breast cancer during the dietary intervention period, mean (SD) age at screening was 62.7 (6.7) years and age at diagnosis was 67.6 (6.9) years. With 516 total deaths, breast cancer overall survival was significantly greater for women in the dietary intervention group than in the usual-diet comparison group (10-year survival of 82% and 78%, respectively; hazard ratio [HR], 0.78; 95% CI, 0.65-0.94; P = .01). In the dietary group there were fewer deaths from breast cancer (68 vs 120; HR, 0.86; 95% CI, 0.64-1.17), other cancers (36 vs 65; HR, 0.76; 95% CI, 0.50-1.17), and cardiovascular disease (27 vs 64; HR, 0.62; 95% CI, 0.39-0.99).

Conclusions and relevance: In women who received a diagnosis of breast cancer during the dietary intervention period, those in the dietary group had increased overall survival. The increase is due, in part, to better survival from several causes of death.

Trial registration: ClinicalTrials.gov Identifier: NCT00000611.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Chlebowski reported being a consultant for Novartis, AstraZeneca, and Genentech. No other disclosures are reported.

Figures

Figure 1.. Participant Flow for Women Who Received a Breast Cancer Diagnosis During the Dietary Intervention Period for Analyses of Breast Cancer Overall Survival

Figure 2.. Dietary Modification Association With Breast Cancer Overall Survival

Kaplan-Meier estimates for breast cancer overall survival (survival from diagnosis with death from any cause) among the 1764 breast cancer cases diagnosed during the dietary intervention period, measured from cancer diagnosis and observed through September 2013. Summary statistics are from a Cox model stratified by age at diagnosis, randomization status in the hormone therapy trials, and study period (intervention period, postintervention period extension 1, or postintervention period extension 2; time dependent). The P value corresponds to a 2-sided score (log-rank) test. Percentages are annualized. HR indicates hazard ratio.

Figure 3.. Forest Plot of Hazard Ratios, Dietary Intervention vs Comparison, for Association of Participant Characteristics With Breast Cancer Overall Survival

Subgroup analysis by participant characteristics (ascertained at baseline except for age at cancer diagnosis) among breast cancer cases diagnosed during the dietary intervention period. Annualized percentages are shown for all subgroups. P values correspond to a test of the interaction between randomization group and subgroup. Analysis for percent energy from fat based on findings in subgroup with 4-day food records. Percentages are annualized. The diamond summarizes the overall influence of dietary intervention on breast cancer overall survival. BMI indicates body mass index, calculated as weight in kilograms divided by height in meters squared; HR, hazard ratio.

Figure 4.. Forest Plot of Hazard Ratios, Dietary Intervention vs Comparison, for Association of Invasive Breast Cancer Characteristics With Breast Cancer Overall Survival

Subgroup analysis by tumor characteristics among breast cancer cases diagnosed during the dietary intervention period. Annualized percentages are shown for all subgroups. P values correspond to a test of the interaction between randomization group and subgroup. Percentages are annualized. The diamond summarizes the overall influence of dietary intervention on breast cancer overall survival. ER indicates estrogen receptor; HR, hazard ratio; PR, progesterone receptor.