Low-fat dietary pattern and breast cancer mortality by metabolic syndrome components: a secondary analysis of the Women's Health Initiative (WHI) randomised trial

Abstract

Background: In the Women's Health Initiative (WHI) dietary modification (DM) randomised trial, the low-fat dietary intervention reduced deaths from breast cancer (P = 0.02). Extending these findings, secondary analysis examined dietary intervention influence on breast cancer mortality by metabolic syndrome (MS) components.

Methods: In total, 48,835 postmenopausal women with no prior breast cancer were randomised to a low-fat dietary intervention or comparison groups. Four MS components were determined at entry in 45,833 participants: (1) high waist circumference, (2) high blood pressure, (3) high cholesterol and (4) diabetes history. Forest plots of hazard ratios (HRs) were generated with P-values for interaction between randomisation groups and MS component score. Primary outcome was death from breast cancer by metabolic syndrome score.

Results: HRs and 95% confidence intervals (CI) for dietary intervention influence on death from breast cancer were with no MS components (n = 10,639), HR 1.09, 95% CI 0.63-1.87; with 1-2 MS components (n = 30,948), HR 0.80, 95% CI 0.62-1.02; with 3-4 MS components (n = 4,246), HR 0.31, 95% CI 0.14-0.69 (interaction P = 0.01).

Conclusions: While postmenopausal women with 3-4 MS components were at higher risk of death from breast cancer, those randomised to a low-fat dietary intervention more likely had reduction in this risk.

Registry: ClinicalTrials.gov (NCT00000611).

Conflict of interest statement

Rowan T. Chlebowski is a consultant for Novartis, AstraZeneca, Genentech, Merck, Immunomedics, and Puma and received honorarium from Novartis and AstraZeneca. None of the other authors report any competing interests related to this study.

© 2021. The Author(s), under exclusive licence to Cancer Research UK.

Figures

Fig. 1. Subgroup analysis by a forest plot of hazard ratios (HRs), dietary intervention versus comparison, for death from breast cancer by select subgroups of participants throughout the cumulative follow-up period.

P-values correspond to a test of the interaction between randomly assigned groups and subgroups. Test of interaction for age, BMI and metabolic syndrome was based on a 1 degree of freedom test for trend. *Did a doctor ever say that you had sugar diabetes or high blood sugar when you were not pregnant? ^Defined as clinic measured systolic and/or diastolic blood pressure ≥130/85mg Hg, or self-report of ever taking antihypertensive medication. †Self-report or use of anti-hyperlipidaemic medications at baseline. ‡Sum of the preceding four baseline indicators: score ranges from 0 (best) to 4 (worst). %, annualised percentage; BMI, body-mass index; P, p-value.

Fig. 2. Subgroup analysis by a forest plot of hazard ratios (HRs), dietary intervention versus comparison, for death after breast cancer by select subgroups of participants throughout the cumulative follow-up period.

See Fig. 1 legend for footnotes and abbreviations.