Dietary Modification and Breast Cancer Mortality: Long-Term Follow-Up of the Women's Health Initiative Randomized Trial

Abstract

Purpose: Observational studies of dietary fat intake and breast cancer have reported inconsistent findings. This topic was addressed in additional analyses of the Women's Health Initiative (WHI) Dietary Modification (DM) clinical trial that evaluated a low-fat dietary pattern influence on breast cancer incidence.

Methods: In the WHI DM trial, 48,835 postmenopausal women, ages 50-79 years, with no prior breast cancer, and a dietary fat intake of ≥ 32% of energy were randomly assigned at 40 US centers to a usual diet comparison group (60%) or dietary intervention group (40%). The goals were to reduce fat intake to 20% of energy and increase vegetable, fruit, and grain intake. Breast cancers were confirmed after central medical record review and serial National Death Index linkages to enhance mortality findings.

Results: During 8.5 years of dietary intervention, breast cancer incidence and deaths as a result of breast cancer were nonsignificantly lower in the intervention group, while deaths after breast cancer were statistically significantly lower both during intervention and through a 16.1-year (median) follow-up. Now, after a long-term, cumulative 19.6-year (median) follow-up, the significant reduction in deaths after breast cancer persists (359 [0.12%] v 652 [0.14%] deaths; hazard ratio [HR], 0.85; 95% CI, 0.74 to 0.96; P = .01), and a statistically significant reduction in deaths as a result of breast cancer (breast cancer followed by death attributed to the breast cancer) emerged (132 [0.037%, annualized risk] v 251 [0.047%] deaths, respectively; HR, 0.79; 95% CI, 0.64 to 0.97; P = .02).

Conclusion: Adoption of a low-fat dietary pattern associated with increased vegetable, fruit, and grain intake, demonstrably achievable by many, may reduce the risk of death as a result of breast cancer in postmenopausal women.

Trial registration: ClinicalTrials.gov NCT00000611.

FIG 1.

Participant flow diagram for the Women’s Health Initiative (WHI) Dietary Modification (DM) trial of a low-fat dietary pattern through extended follow-up. NDI, National Death Index.

FIG 2.

Z statistics that correspond to hazard ratio estimates, starting at random assignment through each additional year of cumulative follow-up. Dotted lines indicate nominal significance at the .05 and .01 levels. As seen, evidence for deaths as a result of breast cancer, a less common event, has incrementally strengthened over the past decade. ER, estrogen receptor; PR, progesterone receptor.

FIG 3.

Dietary modification influence on deaths as a result of breast cancer during cumulative follow-up. Kaplan-Meier cumulative hazard estimates for death as a result of breast cancer during the 19.6-year (median) cumulative follow-up among all 48,835 trial participants. Background shading shows the distribution for duration of the intervention phase (in quintiles); no shading indicates postintervention follow-up for all participants. Summary statistics are from a Cox proportional hazards regression model stratified by age-group, random assignment in the hormone therapy trials, hysterectomy status, ethnicity (white, black, other), and study period (time dependent). The P value corresponds to a 2-sided score (log-rank) test. HR, hazard ratio.