Background: The WHI Diet Modification (DM) trial randomized 48,835 postmenopausal women with no prior breast cancer to a low-fat dietary intervention or comparison group. After 16.1 years follow-up, the intervention was associated with an 18% reduction in risk of death after breast cancer (P =0.01), with greater reduction (29%) in those with waist circumference≥88 cm (J Clin Oncol 2017). To extend these findings, we examined the influence of the dietary intervention on breast cancer mortality in subgroups defined by number of metabolic syndrome (MS) components with 19.6 years median cumulative follow-up. Methods: WHI DM has been previously described. Four MS components were determined at entry: 1) waist circumference≥ 88 cm, 2) high blood pressure or anti-hypertensive use, 3) high cholesterol history and 4) diabetes history, with women categorized as having 0 (n=10,639), 1-2 (n=30,948), or 3-4 (n=4,246) MS components. Forest plots of hazard ratios (HRs) were generated with P-values for interaction between randomized group assignment and number of MS components. Results: Women with 3-4 MS components were more likely to be Black, be obese (BMI ≥30), and have diabetes (all P < 0.001). Breast cancers in women with 3-4 MS components were less likely to be local stage (P = 0.005) or well differentiated (P = 0.03). The magnitude of reduction in deaths from breast cancer in the dietary intervention vs comparison group increased as the number of MS components increased (interaction P = 0.01). Hazard ratios (HR) and 95% confidence intervals (CI) for death from breast cancer for intervention vs comparison groups for women with 0 MS components was 1.09 95% CI, 0.63-1.87, with risk low in both randomization groups (0.028% and 0.026%, respectively); for women with 1-2 MS components, HR 0.80 95% CI 0.62-1.02; and for women with 3-4 MS components, HR 0.31 95% CI, 0.14-0.69, with risk in the intervention group reduced to 0.026%. Conclusions: Adoption of a low-fat dietary pattern had a greater effect on reducing deaths from breast cancer in women with more MS components, suggesting that this is a high risk group more likely to benefit from the dietary intervention. Clinical trial information: NCT00000611